Neurology. 2017 Mar 24. pii: 10.1212/WNL.0000000000003862. [Epub ahead of print]
OBJECTIVE: To examine whether a polygenic risk score (PRS) derived from APOE4, CLU, and ABCA7 is associated with CSF biomarkers of Alzheimer disease (AD) pathology and whether higher cardiorespiratory fitness (CRF) modifies the association between the PRS and CSF biomarkers. METHODS: Ninety-five individuals from the Wisconsin Registry for Alzheimer's Prevention were included in these cross-sectional analyses... [read more]
PLoS One. 2017 Mar 14;12(3):e0173982. eCollection 2017.
Brain changes associated with Alzheimer's disease (AD) begin decades before disease diagnosis. While β-amyloid plaques and neurofibrillary tangles are defining features of AD, neuronal loss and synaptic pathology are closely related to the cognitive dysfunction... [read more]
J Neurosurg. 2017 Mar 10:1-9. [Epub ahead of print]
OBJECTIVE This article describes the use of ultrasound measurements of physical strain within carotid atherosclerotic plaques as a measure of instability and the potential for vascular cognitive decline, microemboli, and white matter changes. METHODS Asymptomatic patients with significant (> 60%) carotid artery stenosis were studied for dynamic measures of plaque instability, presence of microemboli, white matter changes, and vascular cognitive decline in comparison with normative controls and premorbid state... [read more]
Brain and Behavior. 2017 Feb 17;7(3):e00625. eCollection 2017.
Cardiorespiratory fitness (CRF) has been shown to be related to brain health in older adults. In individuals at risk for developing Alzheimer’s disease (AD), CRF may be a modifiable risk factor that could attenuate anticipated declines in brain volume and episodic memory... [read more]
Brain Imaging Behav. 2017 Jan 23. [Epub ahead of print]
Alzheimers Dement (Amst). 2017; 7: 48–55.
Introduction Capillary hypoperfusion is reported in asymptomatic adults at-risk for Alzheimer's disease (AD), but the extent that can be explained by reduced flow in intracranial arteries is unknown. Methods One hundred fifty-five asymptomatic adults enriched for AD risk (mean age 61 years) completed arterial spin labeling (pcASL) and 4D-flow MRI sequences. Voxel-wise regression models investigated the relationship between mean flow in bilateral cerebral arteries and capillary perfusion, and tested potential moderators of this relationship. Results Mean arterial blood flow through middle cerebral arteries (MCAs) and internal carotid arteries was positively associated with perfusion in large cortical clusters (p < .05, false discovery rate corrected)... [read more]
J Alzheimers Dis. 2016 Dec 1. [Epub ahead of print]
The objective of this study was to examine the association of chronotropic response (CR) and heart rate (HR) recovery- two indices of cardiovascular function within the context of a graded exercise test- with cognitive performance in a cognitively healthy, late-middle-aged cohort at risk for Alzheimer's disease (AD). Ninety participants (age = 63.52±5.86 years; 65.6% female) from the Wisconsin Registry for Alzheimer's Prevention participated in this study... [read more]
JAMA Neurol. 2016 Nov 14. [Epub ahead of print]
Importance: The accumulation of aggregated β-amyloid and tau proteins into plaques and tangles is a central feature of Alzheimer disease (AD). While plaque and tangle accumulation likely contributes to neuron and synapse loss, disease-related changes to oligodendrocytes and myelin are also suspected of playing a role in development of AD dementia... [read more]
J Int Neuropsychol Soc. 2016 Nov;22(10):1016-1025.
OBJECTIVES: Intraindividual cognitive variability (IICV) has been shown to differentiate between groups with normal cognition, mild cognitive impairment (MCI), and dementia. This study examined whether baseline IICV predicted subsequent mild to moderate cognitive impairment in a cognitively normal baseline sample. METHODS: Participants with 4 waves of cognitive assessment were drawn from the Wisconsin Registry for Alzheimer's Prevention (WRAP; n=684; 53.6(6.6) baseline age; 9.1(1.0) years follow-up; 70% female; 74.6% parental history of Alzheimer's disease)... [read more]
Journal of Alzheimer’s Disease. 2016 Oct 18;54(4):1395-1408.
It is not known whether computerized cognitive assessments, like the CogState battery, are sensitive to preclinical cognitive changes or pathology in people at risk for Alzheimer’s disease(AD). In 469 late middle-aged participants from the Wisconsin Registry for Alzheimer’s Prevention(mean age 63.8±7 years at testing; 67% female; 39% APOE4+), we examined relationships between a CogState abbreviated battery(CAB) of seven tests and demographic characteristics; traditional paper-based neuropsychological tests as well as a composite cognitive impairment index; cognitive impairment status(determined by consensus review); and biomarkers for amyloid and tau(CSF phosphorylated-tau/Aβ42 and global PET-PiB burden) and neural injury(CSF neurofilament light protein)... [read more]
PLoS One. 2016 Oct 5;11(10):e0163774.
Alterations to myelin may be a core pathological feature of neurodegenerative diseases. Although white matter microstructural differences have been described in Parkinson's disease (PD), it is unknown whether such differences include alterations of the brain's myelin content... [read more]
Journal of Alzheimer’s Disease. 2016 Sep 21. [Epub ahead of print]
Polygenic risk scores (PRSs) have been used to combine the effects of variants with small effects identified by genome-wide association studies. We explore the potential for using pathway-specific PRSs as predictors of early changes in Alzheimer’s disease (AD)-related biomarkers and cognitive function... [read more]
J Alzheimers Dis. 2016 Sep 12. [Epub ahead of print]
Connected language is often impaired among people with Alzheimer’s disease (AD), yet little is known about when language difficulties first emerge on the path to a clinical diagnosis. The objective of this study was to determine whether individuals with psychometric (preclinical) evidence of amnestic mild cognitive impairment (pMCI) showed deficits in connected language measures... [read more]
J Cereb Blood Flow Metab. 2016 Aug 4. pii: 0271678X16661340. [Epub ahead of print]
Cerebral blood flow, arterial pulsation, and vasomotion may be important indicators of cerebrovascular health in aging and diseases of aging such as Alzheimer's disease. Noninvasive markers that assess these characteristics may be helpful in the study of co-occurrence of these diseases and potential additive and interacting effects... [read more]
Journal of Cerebral Blood Flow and Metabolism. 2016 Aug 3. pii: 0271678X16663214. [Epub ahead of print]
Insulin resistance (IR) is associated with poor cerebrovascular health and increased risk for dementia. Little is known about the unique effect of IR on both micro- and macrovascular flow particularly in midlife when interventions against dementia may be most effective... [read more]
Alzheimers Dement. 2016 Jul;12(7):805-14.
INTRODUCTION: The current study investigated the relationship between beta-amyloid (Aβ) and cognition in a longitudinal cohort of late middle-aged participants enriched for Alzheimer’s disease (AD) risk due to parental history of the disease. METHODS: 184 participants (mean age=60; 72% with a parental history of AD) completed a [C-11]PiB positron emission tomography scan and serial cognitive evaluations... [read more]
Neurobiol Aging. 2016 Jul;43:79-88.
Human aging is accompanied by progressive changes in executive function and memory, but the biological mechanisms underlying these phenomena are not fully understood. Using neurite orientation dispersion and density imaging, we sought to examine the relationship between age, cellular microstructure, and neuropsychological scores in 116 late middle-aged, cognitively asymptomatic participants... [read more]
Brain. 2016 Jun 20. pii: aww142. [Epub ahead of print]
The ability to detect preclinical Alzheimer’s disease is of great importance, as this stage of the Alzheimer’s continuum is believed to provide a key window for intervention and prevention. As Alzheimer’s disease is characterized by multiple pathological changes, a biomarker panel reflecting co-occurring pathology will likely be most useful for early detection... [read more]
Diabetes Care. 2016 Jun;39(6):1056-9. doi: 10.2337/dc15-2331. Epub 2016 Apr 8.
OBJECTIVE: We assessed whether the apolipoprotein ε4 (APOE4) genotype affects the relationship of variability in long-term glycemic control (measured by HbA1c SD of multiple measurements) with white matter hyperintensities (WMHs) in elderly patients with type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: WMH volume was generated from structural T1 and fluid-attenuated inversion recovery MRI in each subject. The analysis included 124 subjects; 27 (21.8%) had one or more APOE4 alleles. RESULTS: HbA1c variability was associated with significantly higher WMH in APOE4 carriers (r = 0.47, P = 0.03), controlling for age, sex, mean HbA1c, number of follow-up years, and a composite of cardiovascular risk factors, but not in noncarriers (r = -0.04, P = 0.71; P for interaction = 0.050). CONCLUSIONS: The results suggest that the APOE4 genotype affects the relationship of long-term glycemic control with WMH load so that APOE4 carriers may be more vulnerable to the insults of poor control.... [read more]
Arch Clin Neuropsychol. 2016 May 8. pii: acw024. [Epub ahead of print]
OBJECTIVE: Detecting cognitive decline in presymptomatic Alzheimer's disease (AD) and early mild cognitive impairment (MCI) is challenging, but important for treatments targeting AD-related neurodegeneration. The current study aimed to investigate the utility and performance of internally developed robust norms and standard norms in identifying cognitive impairment in late middle-age (baseline age range = 36-68; M = 54)... [read more]
J Alzheimers Dis. 2016 Apr 12;52(4):1373-83.
Background: Type 2 diabetes is associated with an increased risk for Alzheimer’s disease (AD). Regulation of normal insulin function may be important in reducing the prevalence of dementia due to AD, particularly in individuals who harbor genetic risk for or have a parental family history of AD... [read more]
Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring (Amst). 2016 Apr 9;4:14-7.
INTRODUCTION: Physical activity (PA) is associated with brain health in older adults. However, it is unknown whether the current physical activity recommendations (PAR) impart substantive benefit... [read more]
Journal of the International Neuropsychological Society. 2016 Feb;22(2):191-204.
The purpose of this study was to assess whether age-related differences in white matter microstructure are associated with altered task-related connectivity during episodic recognition.Using functional magnetic resonance imaging and diffusion tensor imaging from 282 cognitively healthy middle-to-late aged adults enrolled in the Wisconsin Registry for Alzheimer's Prevention, we investigated whether fractional anisotropy (FA) within white matter regions known to decline with age was associated with task-related connectivity within the recognition network.There was a positive relationship between fornix FA and memory performance, both of which negatively correlated with age. Psychophysiological interaction analyses revealed that higher fornix FA was associated with increased task-related connectivity amongst the hippocampus, caudate, precuneus, middle occipital gyrus, and middle frontal gyrus... [read more]
Aging Cell. 2016 Feb 1;15(1):100-10.
The hippocampus is critical for cognition and memory formation and is vulnerable to age-related atrophy and loss of function. These phenotypes are attenuated by caloric restriction (CR), a dietary intervention that delays aging... [read more]
Journal of Alzheimer's Disease. 2016 Jan 22;50(3):873-886. [Epub ahead of print]
BACKGROUND: The immune response in Alzheimer's disease (AD) involves activation of microglia which may remove amyloid-β (Aβ). However, overproduction of inflammatory compounds may exacerbate neural damage in AD... [read more]
Alzheimers Dement (Amst). 2016;2:27-38.
INTRODUCTION: Biomarkers are urgently needed for the critical yet understudied preclinical stage of Alzheimer's disease (AD). METHODS: CSF collection, [C-11]PiB amyloid imaging, and MRI were acquired in n=104 cognitively healthy adults enriched with risk for sporadic AD... [read more]
Frontiers in Aging Neuroscience. 2015 Dec 24;7:237.
Healthy aging is associated with brain changes that reflect an alteration to a functional unit in response to the available resources and architecture. Even before the onset of noticeable cognitive decline, the neural scaffolds underlying cognitive function undergo considerable change... [read more]
Brain Imaging and Behavior. 2015 Dec;9(4):729-36.
This study tested the hypothesis that frequent participation in cognitively-stimulating activities, specifically those related to playing games and puzzles, is beneficial to brain health and cognition among middle-aged adults at increased risk for Alzheimer’s disease (AD). Three hundred twenty-nine cognitively normal, middle-aged adults (age range, 43.2-73.8 years) enrolled in the Wisconsin Registry for Alzheimer’s Prevention (WRAP) participated in this study... [read more]
Brain Imaging and Behavior. 2015 Dec;9(4):690-702
Episodic memory is one of the earliest preclinical symptoms of AD, and has been associated with an upregulation in the BOLD response in the prodromal stage (e.g. MCI) of AD... [read more]
Alzheimer's disease, Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring. 2015 Dec 1; 1(4):420-428.
INTRODUCTION: While cerebrovascular disease has long been known to co-occur with Alzheimer's disease (AD), recent studies suggest an etiologic contribution to AD pathogenesis. We used 4D-Flow magnetic resonance imaging (MRI) to evaluate blood flow and pulsatility indices in the Circle of Willis... [read more]
Journal of Cerebral Blood Flow and Metabolism. 2015 Nov 25. pii: 0271678X15617171. [Epub ahead of print]
Cerebral blood flow, arterial pulsation, and vasomotion play important roles in the transport of waste metabolites out of the brain. Impaired vasomotion results in reduced driving force for the perivascular/glymphatic clearance of beta-amyloid... [read more]
Journal of the International Neuropsychological Society. 2015 Nov; 21(10):841-50.
Objective: To examine cross-sectionally whether higher cardiorespiratory fitness (CRF) might favorably modify amyloid-β (Aβ)-related decrements in cognition in a cohort of late-middle-aged adults at risk for Alzheimer’s disease (AD). Methods: Sixty-nine enrollees in the Wisconsin Registry for Alzheimer’s Prevention participated in this study. They completed a comprehensive neuropsychological exam, underwent 11C Pittsburgh Compound B (PiB)-PET imaging, and performed a graded treadmill exercise test to volitional exhaustion... [read more]
Archives of Clinical Neuropsychology. 2015 Nov;30(7):634-42. Epub 2015 Jul 8.
Higher occupational attainment has previously been associated with increased Alzheimer’s disease (AD) neuropathology when individuals are matched for cognitive function, indicating occupation could provide cognitive reserve. We examined whether occupational complexity (OCC) associates with decreased hippocampal volume and increased whole brain atrophy given comparable cognitive function in middle-aged adults at risk for AD... [read more]
Neurobiology of Aging. 2015 Sep;36(9):2568-76. Epub 2015 May 14.
Midlife may be an ideal window for intervention in Alzheimer's disease (AD). To determine whether sleep is associated with early signs of AD neuropathology (amyloid deposition) in late midlife, we imaged brain amyloid deposits using positron emission tomography with [C-11]Pittsburgh Compound B (PiB), and assessed sleep with the Epworth Sleepiness Scale and the Medical Outcomes Study Sleep Scale in 98 cognitively healthy adults (aged 62.4 ± 5.7 years) from the Wisconsin Registry for Alzheimer's Prevention... [read more]
JAMA Neurology; 2015 Sep 1;72(9):1013-20, In Press
IMPORTANCE: Converging evidence suggests that Alzheimer disease (AD) involves insulin signaling impairment. Patients with AD and individuals at risk for AD show reduced glucose metabolism, as indexed by fludeoxyglucose F 18-labeled positron emission tomography (FDG-PET). OBJECTIVES: To determine whether insulin resistance predicts AD-like global and regional glucose metabolism deficits in late middle-aged participants at risk for AD and to examine whether insulin resistance-predicted variation in regional glucose metabolism is associated with worse cognitive performance. DESIGN, SETTING, AND PARTICIPANTS: This population-based, cross-sectional study included 150 cognitively normal, late middle-aged (mean [SD] age, 60.7 [5.8] years) adults from the Wisconsin Registry for Alzheimer's Prevention (WRAP) study, a general community sample enriched for AD parental history... [read more]
Archives of Clinical Neuropsychology. 2015 Aug;30(5):448-57. Epub 2015 May 29.
This study examined the relationship between phonemic and semantic (category) verbal fluency and cognitive status in the Wisconsin Registry for Alzheimer's Prevention (WRAP), a longitudinal cohort enriched for family history of Alzheimer's disease. Participants were 283 WRAP subjects (age 53.1[6.5] years at baseline); who had completed three waves of assessment, over ~6 years and met psychometric criteria either for "cognitively healthy" (CH) or for psychometric amnestic mild cognitive impairment (aMCI) using an approach that did not consider fluency scores... [read more]
NeuroImage: Clinical. 2015 Aug 22;9:216-22.
Higher local carotid artery strain has previously been shown to be a characteristic of unstable carotid plaques. These plaques may be characterized by microvascular changes that predispose to intraplaque hemorrhage, increasing the likelihood of embolization... [read more]
Alzheimers Dement. 2015 Jun 13. pii: S1552-5260(15)00182
The IEEE Conference on Computer Vision and Pattern Recognition (CVPR), 2015, pp. 4795-4803
Statistical analysis of longitudinal or cross sectionalbrain imaging data to identify effects of neurodegenerative diseases is a fundamental task in various studies in neuroscience. However, when there are systematic variations in the images due to parameters changes such as changes in the scanner protocol, hardware changes, or when combining data from multi-site studies, the statistical analysis becomes problematic... [read more]
JAMA Neurology. 2015 Jun;72(6):699-706.
Importance: Although advancing age is the strongest risk factor for the development of symptomatic Alzheimer’s disease (AD), recent studies have shown that there are individual differences in susceptibility to age-related alterations in the biomarkers of AD pathophysiology. Objective: In this study, we investigated whether cognitive reserve modifies the adverse influence of age on key cerebrospinal fluid (CSF) biomarkers of AD. Design, Setting, and Participants: Cross-sectional cohort of 268 individuals (211 cognitively normal and 57 cognitively impaired) from the Wisconsin Registry for Alzheimer’s Prevention and the Wisconsin Alzheimer’s Disease Research Center participated in this study. They underwent lumbar puncture for collection of CSF samples, from which amyloid-β 42 (Aβ42), total tau (t-tau), and phosphorylated tau (p-tau) were immunoassayed... [read more]
Alzheimer's & Dementia: DADM. 2015 Jun 1;1(2):160-169.
There is a growing interest in understanding how amyloid-β (Aβ) accumulation in preclinical Alzheimer’s disease relates to brain morphometric measures and cognition. Existing investigations in this area have been primarily conducted in older cognitively-normal (CN) individuals... [read more]
The IEEE International Conference on Computer Vision (ICCV), 2015, pp. 1841-1849
Eigenvalue problems are ubiquitous in computer vision, covering a very broad spectrum of applications ranging from estimation problems in multi-view geometry to image segmentation. Few other linear algebra problems have a more mature set of numerical routines available and many computer vision libraries leverage such tools extensively... [read more]
The IEEE International Conference on Computer Vision (ICCV), 2015, pp. 666-674
A variety of studies in neuroscience/neuroimaging seek to perform statistical inference on the acquired brain image scans for diagnosis as well as understanding the pathological manifestation of diseases. To do so, an important first step is to register (or co-register) all of the image data into a common coordinate system... [read more]
Journal of Alzheimer’s Disease. 2015 May 30;46(2):525-33.
Background: Insulin resistance (IR) is linked with the occurrence of pathological features observed in Alzheimer’s disease (AD), including neurofibrillary tangles and amyloid plaques. However, the extent to which IR is associated with AD pathology in the cognitively asymptomatic stages of preclinical AD remains unclear.Objective: To determine the extent to which IR is linked with amyloid and tau pathology in late-middle-age.Method: Cerebrospinal fluid (CSF) samples collected from 113 participants enrolled in the Wisconsin Registry for Alzheimer’s Prevention study (mean age = 60.6 years), were assayed for AD-related markers of interest: Aβ 42, P-Tau181, and T-Tau... [read more]
Neuroimage. 2015 May 27;118:103-117. [Epub ahead of print]
There is significant interest, both from basic and applied research perspectives, in understanding how structural/functional connectivity changes can explain behavioral symptoms and predict decline in neurodegenerative diseases such as Alzheimer's disease (AD). The first step in most such analyses is to encode the connectivity information as a graph; then, one may perform statistical inference on various 'global' graph theoretic summary measures (e.g., modularity, graph diameter) and/or at the level of individual edges (or connections)... [read more]
Clin Neuropsychol. 2015 May;29(4):426-41 Epub 2015 May 27.
BACKGROUND: In the last five years, a consensus has developed that Alzheimer's disease (AD) may begin years before overt cognitive impairment. Accordingly, the focus has shifted to identifying preclinical disease in order to match treatments to those most likely to benefit... [read more]
Alzheimers Dement. 2015 May;11(5):504-510.e1. Epub 2014 Jul 17.
BACKGROUND: Insulin resistance (IR) increases Alzheimer's disease (AD) risk. IR is related to greater amyloid burden post-mortem and increased deposition within areas affected by early AD... [read more]
Alzheimer’s and Dementia. 2015 Jun 18. pii: S1552-5260(15)00192-2. [Epub ahead of print]
The mild cognitive impairment (MCI) stage of Alzheimer's disease (AD) may be optimal for clinical trials to test potential treatments for preventing or delaying decline to dementia. However, MCI is heterogeneous in that not all cases progress to dementia within the time frame of a trial and some may not have underlying AD pathology... [read more]
Biomedical Imaging (ISBI), 2015 IEEE 12th International Symposium on , pp.1548-1551, 16-19 April 2015
Statistical data analysis plays a major role in discovering structural and functional imaging phenotypes for mental disorders such as Alzheimer's disease (AD). The goal here is to identify, ideally early on, which regions in the brain show abnormal variations with a disorder... [read more]
Journal of Alzheimer’s Disease, 2015;45(4):1149-55
Cognitive decline is one of the hallmark features of Alzheimer's disease, but many studies struggle to find strong associations between cognitive function and genetic variants. In order to identify which aspects of cognition are more likely to have a strong genetic component, we assessed the heritability of various cognitive functions related to Alzheimer's disease in 303 initially asymptomatic middle-aged adult siblings with a parental history of Alzheimer's disease from the Wisconsin Registry for Alzheimer's Prevention... [read more]
Alzheimer's & Dementia: DADM. 2015 Mar;1(1):33-40.
Background: Subjective memory complaints (SMCs) represent an individual’s perception of subtle changes in memory in the absence of objective impairment in memory. However, it is not fully known whether persons with SMCs harbor brain alterations related to Alzheimer’s disease (AD) or whether they indeed demonstrate poorer cognitive performance. Methods: Participants were 261 middle-aged adults (mean age=54.30 years) enrolled in the Wisconsin Registry for Alzheimer’s Prevention, a registry of cognitively normal adults at risk for AD... [read more]
Current Physical Medicine and Rehabilitation Reports. March 2015, Volume 3, Issue 1, pp 86-97
Dysphagia is common in patients with dementia of varying types and often results in serious health consequences, including malnutrition, dehydration, aspiration pneumonia, and even death. Due to progressive cognitive and functional decline, patients with dementia experience difficulties throughout the eating process which encompasses all aspects of self-feeding and swallowing function... [read more]
Neuroimage. 2015 Jan 15;105:357-68. Epub 2014 Oct 29.
Positive cerebrospinal fluid (CSF) biomarkers of tau and amyloid beta42 suggest possible active underlying Alzheimer's disease (AD) including neurometabolic dysfunction and neurodegeneration leading to eventual cognitive decline. But the temporal relationship between CSF, imaging markers of neural function, and cognition has not been described... [read more]
Med Image Anal. 2015 Apr;21(1):15-28
3D q-space can be viewed as the surface of a 4D hypersphere. In this paper, we seek to develop a 4D hyperspherical interpretation of q-space by projecting it onto a hypersphere and subsequently modeling the q-space signal via 4D hyperspherical harmonics (HSH)... [read more]
Journal of Nuclear Medicine. 2014 Dec;55(12):1973-9.
The serotonin-1A (5-HT1A) receptor is implicated in an array of neurological and psychiatric disorders. Current PET radioligands targeting 5-HT1A receptors have limitations hindering widespread PET studies of this receptor system... [read more]
Brain Imaging and Behavior. 2014 Dec 16. [Epub ahead of print]
Subtle cognitive and behavioral changes are common in early Parkinson's disease. The cause of these symptoms is probably multifactorial but may in part be related to extra-striatal dopamine levels... [read more]
Comput Vis ECCV. 2014; 8690:251-267
Canonical correlation analysis (CCA) is a widely used statistical technique to capture correlations between two sets of multi-variate random variables and has found a multitude of applications in computer vision, medical imaging and machine learning. The classical formulation assumes that the data live in a pair of vector spaces which makes its use in certain important scientific domains problematic... [read more]
Neurology. 2014 Nov 4;83(19):1753-60.
Objective: To examine whether engagement in physical activity might favorably alter the age-dependent evolution of Alzheimer’s disease (AD)-related brain and cognitive changes in a cohort of at-risk, late-middle-aged adults. Methods: Three hundred and seventeen enrollees in the Wisconsin Registry for Alzheimer’s Prevention underwent T1 MRI; a subset also underwent PiB-PET (n=186) and FDG-PET (n=152) imaging. Participants’ responses on a self-report measure of current physical activity were used to classify them as either Physically Active or Physically Inactive based on American Heart Association guidelines... [read more]
Brain Imaging and Behavior. 2014 Oct 16. [Epub ahead of print]
Cardiorespiratory fitness (CRF) is an objective measure of habitual physical activity (PA), and has been linked to increased brain structure and cognition. The gold standard method for measuring CRF is graded exercise testing (GXT), but GXT is not feasible in many settings... [read more]
Lancet Neurol. 2014 Oct;13(10):965-6. Epub 2014 Sep 4.
Brain. 2014 Sep;137(Pt 9):2556-63. Epub 2014 Jul 2.
Nearly all adults with Down syndrome show neuropathology of Alzheimer’s disease, including amyloid-β deposition, by their fifth decade of life. In the current study, we examined the association between brain amyloid-β deposition, assessed via in vivo assessments of neocortical Pittsburgh compound B, and scores on an extensive neuropsychological battery of measures of cognitive functioning in 63 adults (31 male, 32 female) with Down syndrome aged 30–53 years who did not exhibit symptoms of dementia... [read more]
Human Brain Mapping. 2014 Aug;35(8):4219-35. Epub 2014 Feb 7.
Precise detection and quantication of white matter hyperintensities (WMH) observed in T2-weighted Fluid Attenuated Inversion Recovery (FLAIR) Magnetic Resonance Images (MRI) is of substantial interest in aging, and age related neurological disorders such as Alzheimer's disease (AD). This is mainly because WMH may reflect comorbid neural injury or cerebral vascular disease burden... [read more]
Synapse. 2014 Aug;68(8):325-31. Epub 2014 Apr 22.
6-[(18)F]-Fluoro-L-dopa (FDOPA) has been widely used as a biomarker for catecholamine synthesis, storage, and metabolism--its intense uptake in the striatum, and fainter uptake in other brain regions, is correlated with the symptoms and pathophysiology of Parkinson's disease (PD). 6-[(18)F]fluoro-m-tyrosine (FMT), which also targets L-amino acid decarboxylase, has potential advantages over FDOPA as a radiotracer because it does not form catechol-O-methyltransferase (COMT) metabolites. The purpose of the present study was to compare the regional distribution of these radiotracers in the brains of PD patients... [read more]
Proc IEEE Comput Soc Conf Comput Vis Pattern Recognit. 2014 Jun 23;2014:2705-2712
Linear regression is a parametric model which is ubiquitous in scientific analysis. The classical setup where the observations and responses, i.e., (xi , yi ) pairs, are Euclidean is well studied... [read more]
Med Image Anal. 2014 Oct;18(7):1002-14
We first propose a large deformation diffeomorphic metric mapping algorithm to align multiple b-value diffusion weighted imaging (mDWI) data, specifically acquired via hybrid diffusion imaging (HYDI). We denote this algorithm as LDDMM-HYDI... [read more]
Neuroimage. 2014 Jun;93 Pt 1:107-23. Epub 2014 Mar 12.
Statistical analysis on arbitrary surface meshes such as the cortical surface is an important approach to understanding brain diseases such as Alzheimer's disease (AD). Surface analysis may be able to identify specific cortical patterns that relate to certain disease characteristics or exhibit differences between groups... [read more]
Neurobiol Aging. 2014 Nov;35(11):2486-94. Epub 2014 May 27.
Cellular studies suggest sphingolipids may cause or accelerate amyloid-beta (Aβ) and tau pathology but in vivo human studies are lacking. We determined cerebrospinal fluid levels of sphingolipids (ceramides and sphingomyelins), amyloid-beta (Aβ1-42, AβX-38, AβX-40, and AβX-42) and tau (T-tau and p-tau181) in 91 cognitively normal individuals, aged 36-69 years, with a parental history of Alzheimer's disease... [read more]
Neuroscience Letters. 2014 May 21;569:38-42.
The rhesus macaque exhibits age-related brain changes similar to humans, making an excellent model of normal aging. Calorie restriction is a dietary intervention that reduces age-related comorbidities in short-lived animals, and its effects are still under study in rhesus macaques... [read more]
The Journal of Neuroscience
The import of acetyl-CoA into the ER lumen by AT-1/SLC33A1 is essential for the N(ε)-lysine acetylation of ER-resident and ER-transiting proteins. A point-mutation (S113R) in AT-1 has been associated with a familial form of spastic paraplegia... [read more]
Human Brain Mapping. 2014 May;35(5):2044-54.
OBJECTIVES: Although age-related brain changes are becoming better understood, midlife patterns of change are still in need of characterization, and longitudinal studies are lacking. The aim of this study was to determine if baseline fractional anisotropy (FA), obtained from diffusion tensor imaging (DTI) predicts volume change over a 4-year interval. EXPERIMENTAL DESIGN: Forty-four cognitively healthy middle-age adults underwent baseline DTI and longitudinal T1-weighted magnetic resonance imaging. Tensor-based morphometry methods were used to evaluate volume change over time. FA values were extracted from regions of interest that included the cingulum, entorhinal white matter, and the genu and splenium of the corpus callosum. Baseline FA was used as a predictor variable, whereas gray and white matter atrophy rates as indexed by Tensor-based morphometry were the dependent variables. PRINCIPAL OBSERVATIONS: Over a 4-year period, participants showed significant contraction of white matter, especially in frontal, temporal, and cerebellar regions (P < 0.05, corrected for multiple comparisons)... [read more]
Med Image Comput Comput Assist Interv. 2014;17(Pt 2):470-8
There is growing body of research devoted to designing imaging-based biomarkers that identify Alzheimer's disease (AD) in its prodromal stage using statistical machine learning methods. Recently several authors investigated how clinical trials for AD can be made more efficient (i.e., smaller sample size) using predictive measures from such classification methods... [read more]
NeuroImage: Clinical. 2014 Apr 21;4:730-42. eCollection 2014.
INTRODUCTION: Little is still known about the effects of risk factors for Alzheimer's disease (AD) on white matter microstructure in cognitively healthy adults. The purpose of this cross-sectional study was to assess the effect of two well-known risk factors for AD, parental family history and APOE4 genotype. METHODS: This study included 343 participants from the Wisconsin Registry for Alzheimer's Prevention, who underwent diffusion tensor imaging (DTI)... [read more]
Neurobiology of Aging. 2014 Apr;35(4):769-76.
White matter hyperintensities (WMH) of presumed vascular origin, as seen on T2-weighted fluid attenuated inversion recovery magnetic resonance imaging, are known to increase with age and are elevated in Alzheimer's disease (AD). The cognitive implications of these common markers are not well understood... [read more]
Cereb Cortex. 2014 Apr;24(4):978-88. Epub 2012 Dec 12.
Cerebral blood flow (CBF) provides an indication of the metabolic status of the cortex and may have utility in understanding preclinical brain changes in persons at risk for Alzheimer’s disease (AD) and related diseases. In this study, we investigated CBF in 327 well-characterized adults including patients with AD (n=28), patients with amnestic mild cognitive impairment (aMCI, n=23), older cognitively-normal adults (OCN, n=24), and asymptomatic middle-aged adults (n=252) with and without family history (FH) of AD... [read more]
Journal of the International Neuropsychological Society. 2014 Apr;20(4):422-33.
The relative influence of amyloid burden, neuronal structure and function, and prior cognitive performance on prospective memory decline among asymptomatic late middle-aged individuals at risk for Alzheimer’s disease (AD) is currently unknown. We investigated this using longitudinal cognitive data from 122 middle-aged adults (21 “Decliners” and 101 “Stables”) enrolled in the Wisconsin Registry for Alzheimer’s Prevention who underwent multimodality neuroimaging (11C-Pittsburgh Compound B (PiB), 18F-fluorodeoxyglucose (FDG), and structural/functional MRI) 5.7±1.4 years (range=2.9-8.9) after their baseline cognitive assessment... [read more]
Nature Communications. 2014 Apr 1;5:3557.
Caloric restriction (CR) without malnutrition increases longevity and delays the onset of age-associated disorders in short-lived species, from unicellular organisms to laboratory mice and rats. The value of CR as a tool to understand human ageing relies on translatability of CR's effects in primates... [read more]
Neurobiol Aging. 2014 Mar;35(3):576-84.
To determine the relationship between amyloid burden and neural function in healthy adults at risk for Alzheimer’s Disease (AD), we used multi-modal imaging with [C-11]Pittsburgh Compound B positron emission tomography (PET), [F-18]Fluorodeoxyglucose (FDG) PET and MRI, together with cognitive measurement in 201 subjects (mean age 60.1, range 46 to 73) from the Wisconsin Registry for Alzheimer’s Prevention (WRAP). Using a qualitative rating, 18% of the sample were strongly amyloid positive (Aβ+), 41% indeterminate (Aβi) and 41% negative (Aβ-)... [read more]
Dementia and Geriatric Cognitive Disorders. 2014;38(1-2):16-30. Epub 2014 Feb 20.
AIM: It is difficult to reliably detect the earliest signs of Alzheimer's disease (AD)-associated cognitive impairment. Our aim was to compare 3 psychometric methods of identifying amnestic mild cognitive impairment (aMCI) in a middle-aged longitudinal cohort enriched for AD risk. METHODS: Wisconsin Registry for Alzheimer's Prevention (WRAP) participants with 3 waves of cognitive assessment over approximately 6 years were coded as meeting each of 3 psychometric aMCI definitions: (a) 'aMCI standard-baseline' used published norms to establish cutoffs for baseline performance; (b) 'aMCI robust-baseline' applied WRAP-specific robust norms to baseline, and (c) 'aMCI robust-multiwave' applied these robust norms across 3 waves of assessment... [read more]
NeuroImage Clinical. 2014 Feb 19;4:604-14.
Some cognitively healthy individuals develop brain amyloid accumulation, suggestive of incipient Alzheimer’s disease (AD), but the effect of amyloid on other potentially informative imaging modalities, such as Diffusion Tensor Imaging (DTI), in characterizing brain changes in preclinical AD requires further exploration. In this study, a sample (N = 139, mean age 60.6, range 46 to 71) from the Wisconsin Registry for Alzheimer's Prevention (WRAP), a cohort enriched for AD risk factors, was recruited for a multimodal imaging investigation that included DTI and [C-11]Pittsburgh Compound B (PiB) positron emission tomography (PET)... [read more]
Proceedings of Medical Image Computing and Computer-Assisted Intervention (MICCAI) 2014, LNCS Vol 8674, 2014, pp 470-478.
There is growing body of research devoted to designing imaging-based biomarkers that identify Alzheimer’s disease (AD) in its prodromal stage using statistical machine learning methods. Recently several authors investigated how clinical trials for AD can be made more efficient (i.e., smaller sample size) using predictive measures from such classification methods... [read more]
Age (Dordr). 2013 Dec;35(6):2215-27. Epub 2013 Mar 6.
Higher systemic levels of the proinflammatory cytokine interleukin-6 (IL-6) were found to be associated with lower gray matter volume and tissue density in old rhesus macaques. This association between IL-6, and these brain indices were attenuated by long-term 30 % calorie restriction (CR)... [read more]
Advances in Neural Information Processing Systems (NIPS). 2013 Dec; 2013:890-898.
Multiple hypothesis testing is a significant problem in nearly all neuroimaging studies. In order to correct for this phenomena, we require a reliable estimate of the Family-Wise Error Rate (FWER)... [read more]
Obesity (Silver Spring). 2013 Jul;21(7):1313-20. Epub 2013 May 19.
Background: Metabolic syndrome (MetS)—a cluster of cardiovascular risk factors—is linked with cognitive decline and dementia. However, the brain changes underlying this link are presently unknown... [read more]
Brain Res. 2013 May 1;1508:1-8.
While moderate calorie restriction (CR) in the absence of malnutrition has been consistently shown to have a systemic, beneficial effect against aging in several animals models, its effect on the brain microstructure in a non-human primate model remains to be studied using post-mortem histopathologic techniques. In the present study, we investigated differences in expression levels of glial fibrillary acid protein (GFAP) and β-amyloid plaque load in the hippocampus and the adjacent cortical areas of 7 Control (ad libitum)-fed and 6 CR male rhesus macaques using immunostaining methods... [read more]
Neurosurgical Focus 2013 Apr;34(4):E8.
Background and Purpose—Functional magnetic resonance imaging (fMRI) has proven to be an effective component of pretreatment planning in patients harboring a variety of different brain lesions. Our group has recently reported significant relationships concerning distances between brain tumor border and area of functional activation (Lesion-to-Activation-Distance; LAD) with regard to patient morbidity and mortality... [read more]
J Int Neuropsychol Soc. 2013 Mar;19(3):349-54.
Recent studies suggest that white matter abnormalities contribute to both motor and non-motor symptoms of Parkinson’s disease. The present study was designed to investigate the degree to which diffusion tensor magnetic resonance imaging (DTI) indices are related to executive function in Parkinson’s patients... [read more]
Psychophysiology. 2013 Apr;50(4):325-33.
Cognitive control is required for correct antisaccade performance. High antisaccade error rates characterize certain psychiatric disorders, but can be highly variable, even among healthy groups... [read more]
Diabetes Care. 2013 Feb;36(2):443-9.
Objective: Insulin resistance dysregulates glucose uptake and other functions in brain areas affected by Alzheimer’s disease. Insulin resistance may play a role in Alzheimer’s disease etiopathogenesis... [read more]
In Advances in Neural Information Processing Systems (NIPS) 25, pp. 1430-1438. 2012.
Multiple Kernel Learning (MKL) generalizes SVMs to the setting where one simultaneously trains a linear classifier and chooses an optimal combination of given base kernels. Model complexity is typ- ically controlled using various norm regularizations on the base kernel mixing coefficients... [read more]
In Advances in Neural Information Processing Systems (NIPS) 25, pp. 1250-1258. 2012.
Hypothesis testing on signals defined on surfaces (such as the cortical surface) is a fundamental component of a variety of studies in Neuroscience. The goal here is to identify regions that exhibit changes as a function of the clinical condition under study... [read more]
Front Aging Neurosci. 2012;4:31.
The aged rhesus macaque exhibits brain atrophy and behavioral deficits similar to normal aging in humans. Here we studied the association between cognitive and motor performance and anatomic and microstructural brain integrity measured with 3T magnetic resonance imaging in aged monkeys... [read more]
J Int Neuropsychol Soc. 2012 Nov;18(6):1006-18.
After traumatic injury the brain undergoes a prolonged period of degenerative change that is paradoxically accompanied by cognitive recovery. The spatiotemporal pattern of atrophy and the specific relationships of atrophy to cognitive changes are ill understood... [read more]
Curr Alzheimer Res. 2012 Oct;9(8):990-7.
Background/Aims: Hypercholesterolemia in midlife increases risk for Alzheimer's disease (AD) and contributes to cerebrovascular dysregulation - an early finding in preclinical AD pathology. Statins improve vascular reactivity, but it is unknown if they increase regional cerebral blood flow (CBF) in individuals at risk for AD... [read more]
Frontiers in Humans Neuroscience. 2012 Jun 19; 6:160. eCollection 2012.
Traumatic brain injury often involves focal cortical injury and white matter (WM) damage that can be measured shortly after injury. Additionally, slowly evolving WM change can be observed but there is a paucity of research on the duration and spatial pattern of long-term changes several years post-injury... [read more]
Diabetes, 2012 May;61(5):1036-42
Insulin signaling dysregulation is related to neural atrophy in hippocampus and other areas affected by neurovascular and neurodegenerative disorders. It is not known if long-term calorie restriction (CR) can ameliorate this relationship through improved insulin signaling, or if such an effect might influence task learning and performance... [read more]
Neuroimaging Clinics of North America 2012;22(2):373-397.
There are several magnetic resonance (MR) imaging techniques that benefit from high-field MR imaging. This article describes a range of novel techniques that are currently being used clinically or will be used in the future for clinical purposes as they gain popularity... [read more]
Neurobiology of Aging 2012 Jul;33(7):1186-93
We aimed to examine whether total intracranial volume (TICV), a marker of premorbid brain size, modified the impact of the apolipoprotein E (apoE) e4 phenotype and ischemic white matter lesions (WMLs) on odds for dementia. The study comprised a population-based sample of 104 demented and 135 nondemented 85-year-olds, and included physical and neuropsychiatric examinations, and head computerized tomography (CT)... [read more]
Hum Brain Mapp. 2013 Sep;34(9):2276-91.
Objectives: To evaluate brain activation using functional magnetic resonance imaging (fMRI) and specifically, activation changes across time associated with practice-related cognitive control during eye movement tasks. Experimental design: Participants were engaged in antisaccade performance (generating a glance away from a cue) while fMR images were acquired during two separate test sessions: (1) at pre-test before any exposure to the task and (2) at post-test, after 1 week of daily practice on antisaccades, prosaccades (glancing toward a target), or fixation (maintaining gaze on a target)... [read more]
International Journal of Psychophysiology 2012;85(2):274-277.
Anti and pro-saccade performance in single or mixed contexts was explored in a large sample of young adults (n=281). ANOVAs were first conducted to evaluate trial type, context and gender effects... [read more]
NeuroImage, 2012 Jul 16;61(4):1277-1286
Functional MRI (fMRI) allows one to study task-related regional responses and task-dependent connectivity analysis using psychophysiological interaction (PPI) methods. The latter affords the additional opportunity to understand how brain regions interact in a task-dependent manner... [read more]
Neurology, 2012 May 29;78(22):1769-76
Objective: To evaluate the longitudinal influence of family history (FH) of Alzheimer disease (AD) and apolipoprotein E4 (APOE4) on brain atrophy and cognitive decline over 4 years among asymptomatic middle-aged individuals. Methods: Participants were cognitively-healthy adults with (FH+,n=60) and without (FH-,n=48) FH of AD (mean age at baseline=54 years) enrolled in the Wisconsin Registry for Alzheimer's Prevention... [read more]
Neuropsychologia, 2012 Apr;50(5):603-11
It is tentatively estimated that 25% of people with early Alzheimer's disease (AD) show impaired awareness of disease-related changes in their own cognition. Research examining both normative self-awareness and altered awareness resulting from brain disease or injury points to the central role of the medial prefrontal cortex (MPFC) in generating accurate self-appraisals... [read more]
Machine Learning and Interpretation in Neuroimaging (MLINI) 2011, Lecture Notes in Artificial Intelligence (LNAI) 7263, pp. 124-131, 2012.
Recently, the field of neuroimaging analysis has seen a large number of studies which use machine learning methods to make predictions about the progression of Alzheimer's Disease (AD) in mildly demented subjects. Among these, Multi-Kernel Learning (MKL) has emerged as a powerful tool for systematically aggregating diverse data views, and several groups have shown that MKL is uniquely suited to combining different imaging modalities into a single learned model... [read more]
PLoS One. 2012; 7(6)
Cerebrospinal fluid (CSF) biomarkers T-Tau and Aβ(42) are linked with Alzheimer's disease (AD), yet little is known about the relationship between CSF biomarkers and structural brain alteration in healthy adults. In this study we examined the extent to which AD biomarkers measured in CSF predict brain microstructure indexed by diffusion tensor imaging (DTI) and volume indexed by T1-weighted imaging... [read more]
J Alzheimers Dis. 2012;32(1):147-56.
Research shows that certain antihypertensives taken during midlife confer Alzheimer's disease (AD) related benefits in later life. We conducted a clinical trial to evaluate the extent to which the angiotensin converting enzyme inhibitor (ACE-I), ramipril, affects AD biomarkers including cerebrospinal fluid (CSF) amyloid-β (Aβ) levels and ACE activity, arterial function, and cognition in participants with a parental history of AD... [read more]
PLoS ONE 2011;6(11):e27504.
Working memory (WM) capacity and WM processing speed are simple cognitive measures that underlie human performance in complex processes such as reasoning and language comprehension. These cognitive measures have shown to be interrelated in behavioral studies, yet the neural mechanism behind this interdependence has not been elucidated... [read more]
Journal of Alzheimer's Disease. 2011;26 Suppl 3:123-33
The role of hypoperfusion in Alzheimer's disease (AD) is a vital component to understanding the pathogenesis of this disease. Disrupted perfusion is not only evident throughout disease manifestation, it is also demonstrated during the pre-clinical phase of AD (i.e., mild cognitive impairment) as well as in cognitively healthy persons at high-risk for developing AD due to family history or genetic factors... [read more]
IEEE Transaction on Medical Imaging. 2011 Oct;30(10):1760-70
Alzheimer’s disease (AD) research has recently witnessed a great deal of activity focused on developing new statistical learning tools for automated inference using imaging data. The workhorse for many of these techniques is the Support Vector Machine (SVM) framework (or more generally kernel based methods)... [read more]
Brain Imaging Behav. 2011 Sep;5(3):203-11.
Although [18F]fluoro-L-dopa [FDOPA] positron emission tomography (PET) has been used as a surrogate outcome measure in Parkinson’s disease therapeutic trials, this biomarker has not been proven to reflect clinical status longitudinally. We completed a retrospective analysis of relationships between computerized sampling of motor performance, FDOPA PET, and clinical outcome scales, repeated over 4 years, in 26 Parkinson’s disease (PD) patients and 11 healthy controls... [read more]
Mov Disord. 2011 Sep;26(11):2032-8.
Progression of Parkinson's disease symptoms is imperfectly correlated with positron emission tomography biomarkers for dopamine biosynthetic pathways. The radiopharmaceutical 6-[(18) F]fluoro-m-tyrosine is not a substrate for catechol-O-methyltransferase and therefore has a more favorable uptake-to-background ratio than 6-[(18) F]fluoro-L-dopa... [read more]
Psychoneuroendocrinology. 2012 Jul;37(7):903-16.
BACKGROUND: Heightened stress reactivity is associated with hippocampal atrophy, age-related cognitive deficits, and increased risk for Alzheimer's disease. This temperament predisposition may aggravate age-associated brain pathology or be reflective of it... [read more]
Movement Disorders; March, 2011, 26(4): 614-20.
Using both a volume of interest (VOI) and whole brain voxel-wise approach, we compared rates of decline of 6-L-[18F]-fluorodopa (FDOPA) positron emission tomography (PET) uptake ipsilateral (IL) and contralateral (CL) to the initially symptomatic limbs over 4.5 years in 26 subjects with Parkinson’s disease (PD) and 11 controls. The VOI approach used six subregions: Head/body of caudate nucleus, whole putamen, and posterior putamen... [read more]
NeuroImage 2011 Mar 15;55(2):574-89. Epub 2010 Dec 10
Alzheimer's Disease (AD) and other neurodegenerative diseases affect over 20 million people worldwide, and this number is projected to significantly increase in the coming decades. Proposed imaging-based markers have shown steadily improving levels of sensitivity/specificity in classifying individual subjects as AD or normal... [read more]
Neurobiol Aging. 2011 Mar;32(3):497-505. Epub 2009 Apr 22.
Previous studies have indicated a decreased risk for developing Alzheimer's disease in anti-inflammatory (AI) drug users. Yet few studies have determined whether AI drug use provides a protective effect against normal age-related changes in the brains of older adults... [read more]
Alzheimers and Dementia 7, 456-465
Objective: Apolipoprotein E (APOE) genotypes are associated with variable risk of developing late onset Alzheimer’s disease (LOAD), with APOE ε4 having higher risk. A variable poly-T length polymorphism at rs10524523, within intron 6 of the TOMM40 gene has been shown to influence age of onset in LOAD, with very long poly-T length associated with earlier disease onset, and short poly-T length associated with later onset... [read more]
Head Neck. 2011 Oct;33 Suppl 1:S14-20.
Swallowing is a complex neurogenic sensorimotor process involving all levels of the neuraxis and a vast number of muscles and anatomic structures. Disruption of any of these anatomic or functional components can lead to swallowing disorders (also known as dysphagia)... [read more]
Advances in Alzheimer's Disease, Handbook of Imaging the Alzheimer Brain. 2011;2:253-63.
The role of hypoperfusion in Alzheimer's disease (AD) is a vital component to understanding the pathogenesis of this disease. Disrupted perfusion is not only evident throughout disease manifestation, it is also demonstrated during the pre-clinical phase of AD (i.e., mild cognitive impairment) as well as in cognitively healthy persons at high-risk for developing AD due to family history or genetic factors... [read more]
J Alzheimers Dis. 2011;26(2):347-54.
Frontal cortical activation is elicited when subjects have been instructed not to initiate a sensorimotor task. The goal of this preliminary fMRI study was to examine BOLD response to a "Do Not Swallow" instruction (an intentional "off-state") in the context of other swallowing tasks in 3 groups of participants (healthy young, healthy old, and early Alzheimer's disease (AD))... [read more]
J Alzheimers Dis. 2011;26 Suppl 3:263-74.
The macrostructural atrophy of Alzheimer's disease (AD) has been fully described. Current literature reports that also microstructural alterations occur in AD since the early stages... [read more]
Health Pscyhology 2011 Jan;30(1):91-8.
OBJECTIVE: This experiment tested the hypothesis that exercise would improve executive function. DESIGN: Sedentary, overweight 7- to 11-year-old children (N = 171, 56% girls, 61% Black, M ± SD age = 9.3 ± 1.0 years, body mass index [BMI] = 26 ± 4.6 kg/m², BMI z-score = 2.1 ± 0.4) were randomized to 13 ± 1.6 weeks of an exercise program (20 or 40 min/day), or a control condition. MAIN OUTCOME MEASURES: Blinded, standardized psychological evaluations (Cognitive Assessment System and Woodcock-Johnson Tests of Achievement III) assessed cognition and academic achievement. Functional MRI measured brain activity during executive function tasks. RESULTS: Intent to treat analysis revealed dose-response benefits of exercise on executive function and mathematics achievement... [read more]
Front Aging Neurosci. 2010 Sep 3;2. pii: 35.
The use of non-steroidal anti-inflammatory drugs (NSAIDs) in humans is associated with brain differences including decreased number of activated microglia. In animals, NSAIDs are associated with reduced microglia, decreased amyloid burden, and neuronal preservation... [read more]
Alzheimers Dement. 2010 Sep;6(5):394-403. Epub 2010 Aug 14.
Background: Brain alterations in structure and function have been identified in people with risk factors for sporadic type Alzheimer’s disease (AD), suggesting that alterations can be detected decades before AD diagnosis. While the effect of Apolipoprotein E (ApoE) ε4 on the brain is well studied, less is known about the effect of family history of AD... [read more]
Neurobiol Aging. epub August 2010. In Press.
Higher serum homocysteine (Hcy) levels in humans are associated with vascular pathology and greater risk for dementia, as well as lower global and regional volumes in frontal lobe and hippocampus. Calorie restriction (CR) in rhesus monkeys (Macaca mulatta) may confer neural protection against age- or Hcy-related vascular pathology... [read more]
Frontiers in Aging Neuroscience (2010). July 15, 2
Dyslipidemia is common in adults and contributes to high rates of cardiovascular disease and may be linked to subsequent neurodegenerative and neurovascular diseases. This study examined whether lower brain volumes and cognition associated with dyslipidemia could be observed in cognitively healthy adults, and whether apolipoprotein E (APOE) genotype or family history of Alzheimer's disease (FHAD) alters this effect... [read more]
Neuroimage. 2010 Jul 1;51(3):987-94. Epub 2010 Mar 15.
Systemic levels of proinflammatory cytokines such as interleukin-6 (IL-6) increase in old age and may contribute to neural atrophy in humans. We investigated IL-6 associations with age in T1-weighted segments and microstructural diffusion indices using MRI in aged rhesus monkeys (Macaca mulatta)... [read more]
Neurobiol Aging. Epub ahead of print: 2010 Jun 10
Rhesus macaques on a calorie restricted diet (CR) develop less age-related disease, have virtually no indication of diabetes, are protected against sarcopenia, and potentially live longer. Beneficial effects of caloric restriction likely include reductions in age-related inflammation and oxidative damage... [read more]
Journal of Neuroscience. 2010, 30(23):7940-7947
Caloric restriction (CR) reduces the pathological effects of aging and extends the lifespan in many species, including nonhuman primates, although the effect on the brain is less well characterized. We used two common indicators of aging, motor performance speed and brain iron deposition measured in vivo using MRI, to determine the potential effect of CR on elderly rhesus macaques eating restricted (n = 24; 13 males, 11 females) and standard diets (n = 17; 8 males, 9 females)... [read more]
Dev Neuropsychol. 2010 May;35(3):257-77.
Structural brain change and concomitant cognitive decline are the seemingly unavoidable escorts of aging. Despite accumulating studies detailing the effects of age on the brain and cognition, the relationship between white matter features and cognitive function in aging have only recently received attention and remain incompletely understood... [read more]
NMR in Biomedicine. 2010 Apr;23(3):286-93.
Arterial spin labeling (ASL) offers MRI measurement of cerebral blood flow (CBF) in vivo, and may offer clinical diagnostic utility in populations such as those with early Alzheimer’s Disease (AD). In the current study, we investigated the reliability and precision of a pseudo-continuous ASL (pcASL) sequence that was performed two or three times within one hour on eight young normal control subjects, and 14 elderly subjects including 11 with normal cognition, 1 with AD and 2 with Mild Cognitive Impairment (MCI)... [read more]
Methods. 2010 Mar;50(3):157-65
Voxel-based morphometry studies have become increasingly common in human neuroimaging over the past several years; however, few studies have utilized this method to study morphometry changes in non-human primates. Here we describe the application of voxel-wise morphometry methods to the rhesus macaque (Macaca mulatta) using the 112RM-SL template and priors (McLaren et al... [read more]
Alzheimers Dement, Mar;6(2):89-97
Among the major impediments to the design of clinical trials for the prevention of Alzheimer's disease (AD), the most critical is the lack of validated biomarkers, assessment tools, and algorithms that would facilitate identification of asymptomatic individuals with elevated risk who might be recruited as study volunteers. Thus, the Leon Thal Symposium 2009 (LTS'09), on October 27-28, 2009 in Las Vegas, Nevada, was convened to explore strategies to surmount the barriers in designing a multisite, comparative study to evaluate and validate various approaches for detecting and selecting asymptomatic people at risk for cognitive disorders/dementia... [read more]
J Alzheimers Dis. 2010;19(3):963-76.
Although it is established that Alzheimer’s disease (AD) leads to cerebral macrostructural atrophy, microstructural diffusion changes have also been observed, but it is not yet known whether these changes offer unique information about the disease pathology. Thus, a multi-modal imaging study was conducted to determine the independent contribution of each modality in moderate to severe AD... [read more]
Dement Geriatr Cogn Disord. 2010;30(1):83-92
AIMS: To examine awareness of memory abilities by groups (healthy control, suspected dementia/mild cognitive impairment, MCI, and diagnosed dementia/MCI), and to describe group differences in the relationship between awareness and cognitive performance in a community sample. METHODS: In a cross-sectional design, 183 subjects were evaluated in a community setting and categorized into 3 groups based on their cognitive performance and reported medical history. Awareness of memory abilities was quantified using a published anosognosia ratio (AR) comparing the estimated to the objective memory performance by subjects... [read more]
Maturitas. 2010 Feb;65(2):131-7.
Factors contributing to increased risk for Alzheimer's disease (AD) include age, sex, genes, and family history of AD. Several risk factors for AD are endogenous; however, accumulating evidence implicates modifiable risk factors in the pathogenesis of AD... [read more]
Science. 2009 Jul 10;325(5937):201-4.
Caloric restriction (CR), without malnutrition, delays aging and extends life span in diverse species; however, its effect on resistance to illness and mortality in primates has not been clearly established. We report findings of a 20-year longitudinal adult-onset CR study in rhesus monkeys aimed at filling this critical gap in aging research... [read more]
Neuroimage. 2009 May 27.
Structural and functional brain images are playing an important role in helping us understand the changes associated with neurological disorders such as Alzheimer's disease (AD). Recent efforts have now started investigating their utility for diagnosis purposes... [read more]
Brain Imaging Behav. 2009 Sep;3(3):233-239. Epub 2009 Apr 15.
Depressive symptoms occurring late in life are an important risk factor for Alzheimer’s disease. The latest research finds that onset of depressive symptoms in late life may herald the development of AD, not only for aMCI patients, but also for cognitively-normal older adults... [read more]
Neuroimage. 2009 Mar 1;45(1):52-9.
Magnetic resonance imaging (MRI) studies of non-human primates are becoming increasingly common; however, the well-developed voxel-based methodologies used in human studies are not readily applied to non-human primates. In the present study, we create a population-average MRI-based atlas collection for the rhesus macaque (Macaca mulatta) that can be used with common brain mapping packages such as SPM or FSL... [read more]
Neuroimage. 2009 Feb 1;44(3):982-91. Epub 2008 Oct 28.
This study examined age-related changes in swallowing from an integrated biomechanical and functional imaging perspective in order to more comprehensively characterize changes in swallowing associated with age. We examined swallowing-related fMRI brain activity and videoflouroscopic biomechanics of three bolus types (saliva, water and barium) in 12 young and 11 older adults... [read more]
Brain. 2009 Feb;132(Pt 2):383-91. Epub 2008 Oct 1.
First-degree family history (FH) of sporadic Alzheimer's disease and the apolipoprotein E epsilon4 allele (APOE4) are risk factors for Alzheimer's disease that may affect brain function prior to onset of clinical symptoms. In this functional MRI (fMRI) study, we used an episodic recognition task that required discrimination of previously viewed (PV) and novel (NV) faces to examine differences in blood oxygen level dependent (BOLD) signal due to risk factors in 74 middle-aged cognitively normal individuals... [read more]
Age Ageing. 2009 Jan;38(1):86-93. Epub 2008 Dec 2.
BACKGROUND: a small number of reports exist on the cognitive effects of soy isoflavones, the findings from which are mixed. Isoflavone efficacy is dependent upon conversion of glycosides contained in soy foods and supplements to the biologically active aglycons... [read more]
Brain and Cognition 2008 Dec;68(3):255-70.
This review provides a summary of the contributions made by human functional neuroimaging studies to the understanding of neural correlates of saccadic control. The generation of simple visually guided saccades (redirections of gaze to a visual stimulus or pro-saccades) and more complex volitional saccades require similar basic neural circuitry with additional neural regions supporting requisite higher level processes... [read more]
Neuroimage. 2008 Aug 15;42(2):503-14. Epub 2008 May 7.
Traumatic brain injury (TBI) is associated with brain volume loss, but there is little information on the regional gray matter (GM) and white matter (WM) changes that contribute to overall loss. Since axonal injury is a common occurrence in TBI, imaging methods that are sensitive to WM damage such as diffusion-tensor imaging (DTI) may be useful for characterizing microstructural brain injury contributing to regional WM loss in TBI... [read more]
Biological Psychiatry 2008 Dec 15;64(12):1042-50.
BACKGROUND: People with schizophrenia and their biological relatives have deficits in executive control processes such as inhibition and working memory as evidenced by performance abnormalities on antisaccade (AS) and ocular motor delayed response (ODR) tasks. METHODS: The present functional magnetic resonance imaging (fMRI) study was conducted to investigate brain activity associated with these putative indices of schizophrenia risk by: 1) directly comparing neural functioning in 15 schizophrenia patients, 13 of their first-degree biological relatives (primarily siblings), and 14 healthy participants; and 2) assessing executive function associated with volitional saccades by using a combination of AS and ODR tasks. RESULTS: Behavioral data showed that patients and relatives both made more volitional saccade errors. Imaging data demonstrated that within the context of preserved activity in some neural regions in patients and relatives, there were two distinct patterns of disruptions in other regions... [read more]
Alzheimers Dement. 2008 Jul;4(4):285-90.
BACKGROUND: An exaggerated recency effect (ie, disproportionate recall of last-presented items) has been consistently observed in the word list learning of patients with Alzheimer's disease (AD). Our study sought to determine whether there were similar alterations in serial position learning among asymptomatic persons at risk for AD as a result of parental family history... [read more]
Brain Imaging and Behavior. vol. 2, no. 2, pp. 94-104. June, 2008.
Hypercholesterolemia in midlife increases the risk of subsequent cognitive decline, neurovascular disease, and Alzheimer’s disease (AD), and statin use is associated with reduced prevalence of these outcomes. While statins improve vasoreactivity in peripheral arteries and large cerebral arteries, little is known about the effects of statins on cerebral hemodynamic responses and cognition in healthy asymptomatic adults... [read more]
J Am Geriatr Soc. 2008 May;56(5):920-34. Epub 2008 Apr 9.
Given the predicted increase in prevalence of Alzheimer's disease (AD) in the coming decades, early detection and intervention in persons with the predementia condition known as mild cognitive impairment (MCI) is of paramount importance. Recent years have seen remarkable advances in the application of neuroimaging and other biomarkers to the study of MCI... [read more]
Cleve Clin J Med. 2008 Mar;75 Suppl 2:S87-93.
Numerous clinical studies suggest a link between elevated cholesterol and increased risk of Alzheimer disease (AD), and the preponderance of data suggests that statin therapy may reduce the risk of AD later in life. The first clinical investigation of statin therapy in patients with AD, the AD Cholesterol-Lowering Treatment (ADCLT) trial, found that atorvastatin 80 mg/day was associated with improvements relative to placebo on some, but not all, cognitive measures after 6 months and 1 year of therapy... [read more]
J Alzheimers Dis. 2008 Mar;13(2):187-97.
BACKGROUND: Statins reduce amyloid-beta (Abeta) levels in the brain and cerebrospinal fluid (CSF) in animals and may thereby favorably alter the pathobiology of AD. It is unclear if statins modify Abeta metabolism or improve cognition in asymptomatic middle-aged adults at increased risk for AD... [read more]
Neuropsychol Dev Cogn B Aging Neuropsychol Cogn. 2008 Mar;15(2):129-45.
The ability to form associations between choice alternatives and their contingent outcomes is an important aspect of learning that may be sensitive to hippocampal dysfunction in memory disorders of aging such as amnestic mild cognitive impairment (MCIa), or early Alzheimer disease. In this preliminary study we examined brain activation using functional magnetic resonance imaging (fMRI) in 12 healthy elderly participants and nine patients with MCIa during an associative learning task... [read more]
Neuropsychologia. 2008;46(6):1667-78. Epub 2007 Dec 17.
In the present study, we used fMRI to examine the influence of age on two other known risk factors for Alzheimer's disease (AD), APOE genotype and parental history of AD (FH status), during episodic encoding (ENC) and metacognitive self-appraisal (SA) paradigms. These paradigms have previously been shown to evoke activity from brain regions that are implicated in AD... [read more]
BMC Med Educ. 2007 Oct 22;7:39.
BACKGROUND: With rapid advances in functional imaging methods, human studies that feature functional neuroimaging techniques are increasing exponentially and have opened a vast arena of new possibilities for understanding brain function and improving the care of patients with cognitive disorders in the clinical setting. There is a growing need for medical centers to offer clinically relevant functional neuroimaging courses that emphasize the multifaceted and multidisciplinary nature of this field... [read more]
Arch Gen Psychiatry. 2007 Oct;64(10):1163-71.
CONTEXT: Asymptomatic middle-aged adult children of patients with Alzheimer disease (AD) recently were found to exhibit functional magnetic resonance imaging (fMRI) deficits in the mesial temporal lobe during an encoding task. Whether this effect will be observed on other fMRI tasks is yet unknown... [read more]
J Int Neuropsychol Soc. 2007 May;13(3):450-61.
Awareness of cognitive dysfunction shown by individuals with Mild Cognitive Impairment (MCI), a condition conferring risk for Alzheimer's disease (AD), is variable. Anosognosia, or unawareness of loss of function, is beginning to be recognized as an important clinical symptom of MCI... [read more]
J Neurotrauma. 2007 May;24(5):766-71.
Neuropathological and experimental animal studies indicate that traumatic brain injury (TBI) results in long-term, neurodegenerative changes. Structural image evaluation using normalization of atrophy (SIENA) offers an automated analysis of the subtle changes in percent brain volume change (%BVC) associated with TBI... [read more]
Brain Imaging Behav. 2007;1(1-2):3-10.
Voxel-based morphometry (VBM) was used to examine the relationship between gray matter (GM) volume and performance on two commonly used clinical neuropsychological measures of frontal lobe or executive function, the Trail Making Test part B (TrailsB) and the Controlled Oral Word Association Test (COWAT) in 221 cognitively healthy adults between the ages of 18 and 84. We hypothesized that these measures would be associated with GM volume in the dorsolateral frontal lobes... [read more]
Neurosci Biobehav Rev. 2007;31(4):585-96.
We argue that many similar findings observed in cognitive, affective, and social neuroimaging research may compose larger processes central to generating self-relevance. In support of this, recent findings from these research domains were reviewed to identify common systemic activation patterns... [read more]
Hum Brain Mapp. 2007;28(7):654-62.
Caffeine ingestion results in increased brain cell metabolism (Nehlig et al.  Brain Res Brain Res Rev 17:139-170) and decreased cerebral blood flow (Field et al... [read more]
Neurology. 2006 Dec 12;67(11):2039-41.
We compared fMRI and cognitive data from nine hormone therapy (HT)-naive women with data from women exposed to either opposed conjugated equine estrogens (CEE) (n = 10) or opposed estradiol (n = 4). Exposure to either form of HT was associated with healthier fMRI response; however, CEE-exposed women exhibited poorer memory performance than either HT-naive or estradiol-exposed subjects... [read more]
Neuropsychologia. 2006;44(5):762-73. Epub 2005 Sep 8.
Individuals who have sustained a traumatic brain injury (TBI) often exhibit an array of cognitive deficits, yet perhaps most maladaptive of these sequelae is the frequent occurrence of reduced insight into one's own condition. In such cases, TBI individuals may overestimate their post-injury level of socio-cognitive functioning, leading to disparities between how they perceive themselves and what others observe... [read more]
Neuroimage. 2006 Aug 1;32(1):325-32. Epub 2006 Jun 2.
The analysis of functional magnetic resonance imaging (fMRI) data has typically relied on univariate methods to identify areas of brain activity related to cognitive and behavioral task performance. We investigated the ability of multivariate network analysis using a modified form of principal component analysis, the Scaled Subprofile Model (SSM), applied to single-subject fMRI data to identify patterns of interactions among brain regions over time during an anatomically well-characterized simple motor task... [read more]
J Alzheimers Dis. 2006 Aug;9(3):253-60.
OBJECTIVE: To examine the relationship between commonly used screening cognitive measures with gray and white matter integrity in patients with mild to moderate AD. BACKGROUND: New neuroimaging techniques, such as voxel-based morphometry (VBM), make it possible to study the relationship between structural brain integrity and cognitive functioning in AD... [read more]
Curr Alzheimer Res. 2006 Jul;3(3):247-57.
We have pursued an interdisciplinary research program to develop novel behavioral assessment tools for evaluating specific memory impairments following damage to the medial temporal lobe, including the hippocampus and associated structures that show pathology early in the course of Alzheimer's disease (AD). Our approach uses computational models to identify the functional consequences of hippocampal-region damage, leading to testable predictions in both rodents and humans... [read more]
J Neurosci. 2006 May 31;26(22):6069-76.
First-degree family history of sporadic Alzheimer disease (AD) and the apolipoprotein E epsilon4 (APOE4) are risk factors for developing AD. Although the role of APOE4 in AD pathogenesis has been well studied, family history remains a rarely studied and poorly understood risk factor... [read more]
Neuroimage. 2006 Apr 15;30(3):1050-8. Epub 2005 Dec 2.
The anterior medial prefrontal cortex (aMPFC) is consistently active during personally salient decisions, yet the differential contributory processes of this region along the dorsal-ventral axis are less understood. Using a self-appraisal decision-making task and functional magnetic resonance imaging, we demonstrated task-dependent connectivity of ventral aMPFC with amygdala, insula, and nucleus accumbens, and dorsal aMPFC connectivity with dorsolateral PFC and bilateral hippocampus... [read more]
Neuroimage. 2006 Feb 1;29(3):868-78. Epub 2005 Oct 21.
Brodmann's areas are part of the common vernacular used by neuroscientists to indicate specific location of brain activity in functional brain imaging studies. Here, we have employed a template based on the Brodmann's areas as a means of compartmentalizing underlying white matter pathways... [read more]
Neuroimage. 2006 Jan 15;29(2):485-92. Epub 2005 Aug 15.
Neuroimaging research has demonstrated that the posterior cingulate cortex (PCC) is functionally compromised in individuals diagnosed with amnestic mild cognitive impairment (MCI), a major risk factor for the development of Alzheimer's disease (AD). In functional MRI studies with healthy participants, this same region is active during self-appraisal (requiring retrieval of semantic knowledge about the self) as well as episodic recognition of previously learned information... [read more]
BMC Med. 2006 Jan 13;4:1.
BACKGROUND: The presence of the apolipoprotein E (APOE) epsilon4 allele is a major risk factor for the development of Alzheimer's disease (AD), and has been associated with metabolic brain changes several years before the onset of typical AD symptoms. Functional MRI (fMRI) is a brain imaging technique that has been used to demonstrate hippocampal activation during measurement of episodic encoding, but the effect of the epsilon4 allele on hippocampal activation has not been firmly established... [read more]
Alzheimers Dement. 2006;2(4):296-302.
BACKGROUND: Several previous studies have reported that amnestic mild cognitive impairment (aMCI), a significant risk factor for Alzheimer's disease (AD), is associated with greater atrophy in the medial temporal lobe (MTL) and posterior cingulate gyrus (PCG). METHOD: In the present study, we examined the cross-sectional accuracy (i.e., the sensitivity and specificity) of voxel-based morphometry (VBM) in discriminating individuals with MCI (n =15) from healthy age-matched controls (n =15)... [read more]
BMC Neurol. 2005 Dec 2;5:23.
BACKGROUND: Obesity causes or exacerbates a host of medical conditions, including cardiovascular, pulmonary, and endocrine diseases. Recently obesity in elderly women was associated with greater risk of dementia, white matter ischemic changes, and greater brain atrophy... [read more]
J Cogn Neurosci. 2005 Dec;17(12):1897-906.
The anterior medial prefrontal (AMPFC) and retrosplenial (RSC) cortices are active during self-referential decision-making tasks such as when participants appraise traits and abilities, or current affect. Other appraisal tasks requiring an evaluative decision or mental representation, such as theory of mind and perspective-taking tasks, also involve these regions... [read more]
J Int Neuropsychol Soc. 2004 Nov;10(7):939-47.
The Hooper Visual Organization Test (VOT), a commonly applied neuropsychological test of visual spatial ability, is used for assessing patients with suspected right hemisphere, or parietal lobe involvement. A controversy has developed over whether the inferences of this test metric can be assumed to involve global, lateralized, or regional functionality... [read more]
Neuroimage. 2004 Sep;23(1):167-74.
Voxel-based morphometric (VBM) investigations of temporal lobe epilepsy have focused on the presence and distribution of gray matter abnormalities. VBM studies to date have identified the expected abnormalities in hippocampus and extrahippocampal temporal lobe, as well as more diffuse abnormalities in the thalamus, cerebellum, and extratemporal neocortical areas... [read more]
Neuroimage. 2004 Jun;22(2):941-7.
The capability to foster metacognitive evaluations (MEs) of oneself and others represents a major component of conscious awareness. Separate emerging lines of brain activation research examining ME have converged on the medial prefrontal cortex as a common finding... [read more]
We examined the dynamic process of encoding novel repeating faces using functional MRI (fMRI) in non-demented elderly volunteers with and without diagnosed memory problems. We hypothesized that adaptation (repetition dependent reduction in activity) would occur in the mesial temporal lobe (MTL), and that this would be associated with cognitive status... [read more]
Epilepsia. 2004 Jan;45(1):85-9.
The Wada test has historically been the conventional procedure for determining language lateralization before neurosurgery. However, functional magnetic resonance imaging (fMRI) offers a less invasive alternative to the Wada procedure... [read more]
Neurobiol Aging. 2003 Nov;24(7):947-52.
The Apolipoprotein E (APOE) epsilon 4 allele is an important risk factor for Alzheimer's disease (AD). Given the interest in early identification of at-risk individuals, we examined memory decline as a function of APOE status and age in cognitively intact participants aged 48-77 years old (yo)... [read more]
Brain, Vol. 125, No. 8, 1808-1814, August 2002
The capacity to reflect on one’s sense of self is an important component of self-awareness. In this paper, we investigate some of the neurocognitive processes underlying reflection on the self using functional MRI... [read more]