Publications by authors named "Elizabeth Leritz"

34 Publications

Evidence for a Specific Association Between Sustained Attention and Gait Speed in Middle-to-Older-Aged Adults.

Front Aging Neurosci 2021 5;13:703434. Epub 2021 Jul 5.

Boston Attention and Learning Laboratory (BALLAB), VA Boston Healthcare System, Boston, MA, United States.

Although cognitive decline has previously been associated with mobility limitations and frailty, the relationship between sustained attention and gait speed is incompletely characterized. To better quantify the specificity of the sustained attention and gait speed association, we examined the extent to which this relationship is unique rather than accounted for by executive functioning and physical health characteristics. 58 middle-to-older-aged community-dwelling adults without overt evidence of cognitive impairment (45-90 years old; 21 females) participated in the study. Each participant completed a 4-meter gait speed assessment and validated neuropsychological tests to examine various domains of executive functioning including working memory (i.e., Digit Span), inhibitory control (i.e., D-KEFS Color-Word Interference), and task switching (i.e., D-KEFS Number/Letter Switching). Multiple physical and vascular risk factors were also evaluated. Sustained attention was assessed using the gradual onset continuous performance task (gradCPT), a well-validated go/no-go sustained attention task. A series of linear regression models were used to examine how different aspects of cognition, including sustained attention and traditional measures of executive functioning, related to gait speed while controlling for a variety of physical and vascular risk factors. Among all predictors, gradCPT accuracy explained the most variance in gait speed ( = 0.19, < 0.001) and was the only significant predictor (β = 0.35, = 0.01) when accounting for executive functioning and other physical and vascular risk factors. The present results indicate that sustained attention may be uniquely sensitive and mechanistically linked to mobility limitations in middle-to-older adults.
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http://dx.doi.org/10.3389/fnagi.2021.703434DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8289388PMC
July 2021

Association between metabolic syndrome and resting-state functional brain connectivity.

Neurobiol Aging 2021 08 1;104:1-9. Epub 2021 Apr 1.

Neuroimaging Research for Veterans Center (NeRVe), Geriatric Research Education and Clinical Center (GRECC), VA Boston Healthcare System, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.

The objective of this study is to examine whether metabolic syndrome (MetS), the clustering of 3 or more cardiovascular risk factors, disrupts the resting-state functional connectivity (FC) of the large-scale cortical brain networks. Resting-state functional magnetic resonance imaging data were collected from seventy-eight middle-aged and older adults living with and without MetS (27 MetS; 51 non-MetS). FC maps were derived from the time series of intrinsic activity in the large-scale brain networks by correlating the spatially averaged time series with all brain voxels using a whole-brain seed-based FC approach. Participants with MetS showed hyperconnectivity across the core brain regions with evidence of loss of modularity when compared with non-MetS individuals. Furthermore, patterns of higher between-network MetS-related effects were observed across most of the seed regions in both right and left hemispheres. These findings indicate that MetS is associated with altered intrinsic communication across core neural networks and disrupted between-network connections across the brain due to the co-occurring vascular risk factors in MetS.
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http://dx.doi.org/10.1016/j.neurobiolaging.2021.03.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8225583PMC
August 2021

The role of cognitive reserve in the relationship between metabolic syndrome and cognitive functioning.

Neuropsychol Dev Cogn B Aging Neuropsychol Cogn 2021 09 6;28(5):717-732. Epub 2020 Sep 6.

VA Boston Healthcare System; Boston, Massachusetts, USA.

Metabolic syndrome (MetS) is a cluster of vascular risk factors that can impact cognition. Cognitive reserve (CR), specifically early operators of reserve (e.g., education), have not been explored in the relationship between MetS and cognition. Adults 45-90 years old (n = 149) underwent neuropsychological testing and evaluation for MetS. Exploratory and confirmatory factor analyses defined neuropsychological domains and created a CR score based on early operators of CR. Regression analyses examined the association among MetS, CR, and neuropsychological performance. CFA revealed two neuropsychological factors: Episodic Memory and Executive Functioning. Controlling for age and physical ability, MetS and CR were significant predictors of the Factors. With CR in the model, MetS became a non-significant predictor of Executive Functioning; CR and physical ability were the most significant predictors. CR and MetS significantly predicted Episodic Memory . The results are discussed in the context of neuroprotective factors and cognitive aging.
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http://dx.doi.org/10.1080/13825585.2020.1817304DOI Listing
September 2021

Metabolic Syndrome and Physical Performance: The Moderating Role of Cognition among Middle-to-Older-Aged Adults.

J Int Neuropsychol Soc 2021 02 10;27(2):172-180. Epub 2020 Aug 10.

New England Geriatric Research, Education and Clinical Center, VA Boston Healthcare System, Boston, MA, USA.

Objective: Mobility limitation and cognitive decline are related. Metabolic syndrome (MetS), the clustering of three or more cardiovascular risk factors, is associated with decline in both mobility and cognition. However, the interrelationship among MetS, mobility, and cognition is unknown. This study investigated a proposed pathway where cognition moderates the relationship between MetS and Mobility.

Method: Adults ages 45-90 years were recruited. MetS risk factors and mobility performance (Short Physical Performance Battery (SPPB) and gait speed) were evaluated. Cognition was assessed using a comprehensive neuropsychological battery. A factor analysis of neuropsychological test scores yielded three factors: executive function, explicit memory, and semantic/contextual memory. Multivariable linear regression models were used to examine the relationship among MetS, mobility, and cognition.

Results: Of the 74 participants (average age 61 ± 9 years; 41% female; 69% White), 27 (36%) participants manifested MetS. Mean SPPB score was 10.9 ± 1.2 out of 12 and gait speed was 1.0 ± 0.2 m/s. There were no statistically significant differences in mobility by MetS status. However, increase in any one of the MetS risk factors was associated with decreased mobility performance after adjusting for age and gender (SPPB score: β (SE) -.17 (0.08), p < .05; gait speed: -.03 (.01), p < .01). Further adjusting for cognitive factors (SPPB score: explicit memory .31 (.14), p = .03; executive function 0.45 (0.13), p < .01; gait speed: explicit memory 0.04 (0.02), p = .03; executive function 0.06 (0.02), p < .01) moderated the relationships between number of metabolic risk factors and mobility.

Conclusion: The relationship between metabolic risk factors and mobility may be moderated by cognitive performance, specifically through executive function and explicit memory.
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http://dx.doi.org/10.1017/S1355617720000788DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059433PMC
February 2021

Burden and Patterns of Multimorbidity: Impact on Disablement in Older Adults.

Am J Phys Med Rehabil 2020 05;99(5):359-365

From the Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, University of Texas Health Sciences Center, San Antonio, Texas (MEJ); Boston University School of Public Health, Boston, Massachusetts (PN); New England Geriatric Research Education and Clinical Center, VA Boston Healthcare System, Boston, Massachusetts (JD, EL, JFB); Division of Aging, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts (JD); Department of Psychiatry, Harvard Medical School, Boston, Massachusetts (EL); College of Nursing and Health Sciences, University of Massachusetts Boston, Boston, Massachusetts (SGL); Department of Physical Therapy, MGH Institute of Health Professions, Boston, Massachusetts (AMJ); Department of Physical Medicine and Rehabilitation, Harvard Medical School, Boston, Massachusetts (JFB); and Spaulding Rehabilitation Hospital, Charleston, Massachusetts (JFB).

Objective: The aim of this study was to assess the impact of the burden and patterns of multimorbidity on disability domains.

Design: In a cross-sectional study of 425 older adults from the Boston Rehabilitative Impairment Study of the Elderly, participants self-reported 13 chronic conditions and underwent assessment of body function (leg strength, velocity, and power, trunk extensor endurance, leg range of motion, foot sensation), activities (400-m walk test, Short Physical Performance Battery, Late Life Function and Disability Instrument function scores) and participation (Late Life Function and Disability Instrument participation scores). The association between multimorbidity patterns (identified by latent class analysis) and disablement measures, as well as multimorbidity burden (captured by a multimorbidity score) and disablement measures, was tested.

Results: Latent class analysis identified three classes-low multimorbidity, high multimorbidity, and predominantly musculoskeletal conditions. Class membership (multimorbidity pattern) was not associated with disablement measures, but multimorbidity score was associated with poor performance in all domains. A 1-point higher multimorbidity score was associated with lower scores in body functions (by 0.06 SD unit), activities (0.07-0.10 SD units), as well as participation (0.07-0.09 units).

Conclusion: Multimorbidity counts may be an excellent tool for risk stratification and identification of persons in need of rehabilitation.

To Claim Cme Credits: Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME CME OBJECTIVES: Upon completion of this article, the reader should be able to (1) describe and distinguish the effect of multimorbidity burden and multimorbidity patterns on three disability domains in older adults; (2) identify and discuss possible reasons why high multimorbidity burden may result in a restriction among social participation in older adults; and (3) detect disability risk among older patients during clinical assessment by using a simple count of common chronic conditions.

Level: Advanced ACCREDITATION: The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.The Association of Academic Physiatrists designates this Journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.
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http://dx.doi.org/10.1097/PHM.0000000000001388DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7275931PMC
May 2020

Associations between cerebral blood flow and structural and functional brain imaging measures in individuals with neuropsychologically defined mild cognitive impairment.

Neurobiol Aging 2020 02 6;86:64-74. Epub 2019 Nov 6.

Brain Aging and Dementia (BAnD) Laboratory, MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA, USA; Neuroimaging Research for Veterans (NeRVe) Center, VA Boston Healthcare System, Boston, MA, USA.

Reduced cerebral blood flow (CBF), an indicator of neurovascular processes and metabolic demands, is a common finding in Alzheimer's disease. However, little is known about what contributes to CBF deficits in individuals with mild cognitive impairment (MCI). We examine regional CBF differences in 17 MCI compared with 21 age-matched cognitively healthy older adults. Next, we examined associations between CBF, white matter lesion (WML) volume, amplitude of low-frequency fluctuations, and cortical thickness to better understand whether altered CBF was detectable before other markers and the potential mechanistic underpinnings of CBF deficits in MCI. MCI had significantly reduced CBF, whereas cortical thickness and amplitude of low-frequency fluctuation were not affected. Reduced CBF was associated with the WML volume but not associated with other measures. Given the presumed vascular etiology of WML and relative worsening of vascular health in MCI, it may suggest CBF deficits result from early vascular as opposed to metabolic deficits in MCI. These findings may support vascular mechanisms as an underlying component of cognitive impairment.
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http://dx.doi.org/10.1016/j.neurobiolaging.2019.10.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6995432PMC
February 2020

Aberrant patterns of default-mode network functional connectivity associated with metabolic syndrome: A resting-state study.

Brain Behav 2019 12 30;9(12):e01333. Epub 2019 Sep 30.

Neuroimaging Research for Veterans Center (NeRVe), Geriatric Research Education and Clinical Center (GRECC), VA Boston Healthcare System, Boston, Massachusetts.

Introduction: Metabolic syndrome (MetS) is a clustering of three or more cardiovascular risk factors (RF), including hypertension, obesity, high cholesterol, or hyperglycemia. MetS and its component RFs are more prevalent in older age, and can be accompanied by alterations in brain structure. Studies have shown altered functional connectivity (FC) in samples with individual RFs as well as in clinical populations that are at higher risk to develop MetS. These studies have indicated that the default mode network (DMN) may be particularly vulnerable, yet little is known about the overall impact of MetS on FC in this network.

Methods: In this study, we evaluated the integrity of FC to the DMN in participants with MetS relative to non-MetS individuals. Using a seed-based connectivity analysis approach, resting-state functional MRI (fMRI) data were analyzed, and the FC measures among the DMN seed (isthmus of the cingulate) and rest of the brain voxels were estimated.

Results: Participants with MetS demonstrated reduced positive connectivity between the DMN seed and left superior frontal regions, and reduced negative connectivity between the DMN seed and left superior parietal, left postcentral, right precentral, right superior temporal and right superior parietal regions, after accounting for age- and sex-effects.

Conclusions: Our results suggest that MetS is associated with alterations in FC between the DMN and other regions of the brain. Furthermore, these results indicate that the overall burden of vascular RFs associated with MetS may, in part, contribute to the pathophysiology underlying aberrant FC in the DMN.
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http://dx.doi.org/10.1002/brb3.1333DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6908882PMC
December 2019

Metabolic risk in older adults is associated with impaired sustained attention.

Neuropsychology 2019 Oct 16;33(7):947-955. Epub 2019 May 16.

Geriatric Research, Education, & Clinical Center (GRECC).

Objective: Metabolic syndrome (MetS), the presence of three or more cardiovascular risk factors, has been associated with subtle and diffuse neural compromise but has not been consistently associated with cognitive dysfunction. Sustained attention is a fundamental cognitive operation that relies on multiple brain networks and is impaired in a broad array of neurologic conditions. We examined whether a well-validated measure of sustained attention would be sensitive to vascular risk, as compared with more standard neuropsychological measures of attention and executive functioning.

Method: We assessed vascular risk factors (VRFs; blood pressure, waist circumference, cholesterol, glucose, and triglycerides) in 93 middle-to-older aged adults (45-75 years). MetS was defined based on current guidelines from the National Cholesterol Education Program Adult Training Program (NCEP ATP III). Participants were grouped according to number of VRFs: high risk (MetS; 3+ VRFs; = 32), medium risk (1 or 2 VRFs; = 35), and low risk (0 VRFs; = 26). All participants underwent a neuropsychological battery of tests measuring executive functioning. Participants also performed the gradual-onset continuous performance task (gradCPT), a measure of sustained attention.

Results: There was a significant main effect of VRF group on sustained attention performance; participants with lower vascular risk were better able to sustain attention. No significant effects were detected on standard neuropsychological tests of executive function.

Conclusion: Our results suggest that the gradCPT is sensitive to the potentially negative effects of MetS on subtle aspects of neurocognitive functioning. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
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http://dx.doi.org/10.1037/neu0000554DOI Listing
October 2019

Interrelated Neuromuscular and Clinical Risk Factors That Contribute to Falls.

J Gerontol A Biol Sci Med Sci 2019 08;74(9):1526-1532

New England Geriatric Research and Education Clinical Center (GRECC), VA Boston Healthcare System, Massachusetts.

Background: Neuromuscular and clinical factors contribute to falls among older adults, yet the interrelated nature of these factors is not well understood. We investigated the relationships between these factors and how they contribute to falls, which may help optimize fall risk assessment and prevention.

Methods: A total of 365 primary care patients (age = 77 ± 7, 67% female) were included from the Boston Rehabilitative Impairment Study of the Elderly. Neuromuscular measures included leg strength and leg velocity, trunk extensor endurance, and knee range of motion. Clinical measures included memory, executive function, depressive symptoms, pain, sensory loss, vision, comorbidity, physical activity, mobility self-efficacy, and psychiatric medication. Factor analysis was used to evaluate clustering of factors. Negative binomial regression assessed the relationship of factors with three-year fall rate. Interactions were tested to examine whether clinical factors modified the relationship between neuromuscular factors and falls.

Results: Three factors emerged: (i) neuromuscular factors, pain, and self-efficacy; (ii) memory; and (iii) executive function. Having three neuromuscular impairments predicted higher fall rate (incidence rate ratio [95% confidence interval]: 3.39 [1.82-6.32]) but was attenuated by memory (1.69 [1.10-2.61]), mobility self-efficacy (0.99 [0.98-0.99]), psychiatric medication use (1.54 [1.10-2.14]), and pain (1.13 [1.04-1.23]). Pain modified the relationship between neuromuscular impairment burden (number of neuromuscular impairments) and falls. Having three neuromuscular impairments was associated with a higher fall rate in patients with high levels of pain (5.73 [2.46-13.34]) but not among those with low pain.

Conclusions: Neuromuscular impairment burden was strongly associated with fall rate in older adults with pain. These factors should be considered together during fall risk assessment, post fall assessment, and prevention.
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http://dx.doi.org/10.1093/gerona/glz030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6696708PMC
August 2019

Differential associations of metabolic risk factors on cortical thickness in metabolic syndrome.

Neuroimage Clin 2018 28;17:98-108. Epub 2017 Sep 28.

Neuroimaging Research for Veterans Center (NeRVe), Geriatric Research Education and Clinical Center (GRECC), Veterans Administration Boston Healthcare System, Boston, MA, USA; Harvard Medical School, Boston, MA, USA. Electronic address:

Objective: Metabolic syndrome (MetS) refers to a cluster of risk factors for cardiovascular disease, including obesity, hypertension, dyslipidemia, and hyperglycemia. While sizable prior literature has examined associations between individual risk factors and quantitative measures of cortical thickness (CT), only very limited research has investigated such measures in MetS. Furthermore, the relative contributions of these risk factors to MetS-related effects on brain morphology have not yet been studied. The primary goal of this investigation was to examine how MetS may affect CT. A secondary goal was to explore the relative contributions of individual risk factors to regional alterations in CT, with the potential to identify risk factor combinations that may underlie structural changes.

Methods: Eighteen participants with MetS (mean age = 59.78 years) were age-matched with 18 healthy control participants (mean age = 60.50 years). CT measures were generated from T1-weighted images and groups were contrasted using whole-brain general linear modeling. A follow-up multivariate partial least squares correlation (PLS) analysis, including the full study sample with complete risk factor measurements (N = 53), was employed to examine which risk factors account for variance in group structural differences.

Results: Participants with MetS demonstrated significantly reduced CT in left hemisphere inferior parietal, rostral middle frontal, and lateral occipital clusters and in a right hemisphere precentral cluster. The PLS analysis revealed that waist circumference, high-density lipoprotein cholesterol (HDL-C), triglycerides, and glucose were significant contributors to reduced CT in these clusters. In contrast, diastolic blood pressure showed a significantly positive association with CT while systolic blood pressure did not emerge as a significant contributor. Age was not associated with CT.

Conclusion: These results indicate that MetS can be associated with regionally specific reductions in CT. Importantly, a novel link between a risk factor profile comprising indices of obesity, hyperglycemia, dyslipidemia and diastolic BP and localized alterations in CT emerged. While the pathophysiological mechanisms underlying these associations remain incompletely understood, these findings may be relevant for future investigations of MetS and might have implications for treatment approaches that focus on specific risk factor profiles with the aim to reduce negative consequences on the structural integrity of the brain.
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http://dx.doi.org/10.1016/j.nicl.2017.09.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5641920PMC
June 2018

Contributions of polygenic risk for obesity to PTSD-related metabolic syndrome and cortical thickness.

Brain Behav Immun 2017 Oct 1;65:328-336. Epub 2017 Jun 1.

National Center for PTSD, Behavioral Science Division, VA Boston Healthcare System, Boston, MA, United States; Department of Psychiatry, Boston University School of Medicine, Boston, MA, United States.

Background: Research suggests that posttraumatic stress disorder (PTSD) is associated with metabolic syndrome (MetS) and that PTSD-associated MetS is related to decreased cortical thickness. However, the role of genetic factors in these associations is unclear. This study evaluated contributions of polygenic obesity risk and PTSD to MetS and of MetS and polygenic obesity risk to cortical thickness.

Methods: 196 white, non-Hispanic veterans of the wars in Iraq and Afghanistan underwent clinical diagnostic interviews, physiological assessments, and genome-wide genotyping; 168 also completed magnetic resonance imaging scans. Polygenic risk scores (PRSs) for obesity were calculated from results of a prior genome-wide association study (Speliotes et al., 2010) and PTSD and MetS severity factor scores were obtained.

Results: Obesity PRS (β=0.15, p=0.009) and PTSD (β=0.17, p=0.005) predicted MetS and interacted such that the association between PTSD and MetS was stronger in individuals with greater polygenic obesity risk (β=0.13, p=0.02). Whole-brain vertex-wise analyses suggested that obesity PRS interacted with MetS to predict decreased cortical thickness in left rostral middle frontal gyrus (β=-0.40, p<0.001).

Conclusions: Results suggest that PTSD, genetic variability, and MetS are related in a transactional fashion wherein obesity genetic risk increases stress-related metabolic pathology, and compounds the ill health effects of MetS on the brain. Genetic proclivity towards MetS should be considered in PTSD patients when prescribing psychotropic medications with adverse metabolic profiles. Results are consistent with a growing literature suggestive of PTSD-related accelerated aging.
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http://dx.doi.org/10.1016/j.bbi.2017.06.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5537007PMC
October 2017

Higher serum cholesterol is associated with intensified age-related neural network decoupling and cognitive decline in early- to mid-life.

Hum Brain Mapp 2017 06 31;38(6):3249-3261. Epub 2017 Mar 31.

Neuroimaging Research for Veterans Center, VA Boston Healthcare System, Boston, Massachusetts, 02130.

Mounting evidence indicates that serum cholesterol and other risk factors for cardiovascular disease intensify normative trajectories of age-related cognitive decline. However, the neural mechanisms by which this occurs remain largely unknown. To understand the impact of cholesterol on brain networks, we applied graph theory to resting-state fMRI in a large sample of early- to mid-life Veterans (N = 206, Mean  = 32). A network emerged (centered on the banks of the superior temporal sulcus) that evidenced age-related decoupling (i.e., decreased network connectivity with age), but only in participants with clinically-elevated total cholesterol (≥180 mg/dL). Crucially, decoupling in this network corresponded to greater day-to-day disability and mediated age-related declines in psychomotor speed. Finally, examination of network organization revealed a pattern of age-related dedifferentiation for the banks of the superior temporal sulcus, again present only with higher cholesterol. More specifically, age was related to decreasing within-module communication (indexed by Within-Module Degree Z-Score) and increasing between-module communication (indexed by Participation Coefficient), but only in participants with clinically-elevated cholesterol. Follow-up analyses indicated that all findings were driven by low-density lipoprotein (LDL) levels, rather than high-density lipoprotein (HDL) or triglycerides, which is interesting as LDL levels have been linked to increased risk for cardiovascular disease, whereas HDL levels appear inversely related to such disease. These findings provide novel insight into the deleterious effects of cholesterol on brain health and suggest that cholesterol accelerates the impact of age on neural trajectories by disrupting connectivity in circuits implicated in integrative processes and behavioral control. Hum Brain Mapp 38:3249-3261, 2017. © 2017 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/hbm.23587DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6061952PMC
June 2017

Elevated levels of serum cholesterol are associated with better performance on tasks of episodic memory.

Metab Brain Dis 2016 Apr 12;31(2):465-73. Epub 2016 Feb 12.

Geriatric Research, Education and Clinical Center (GRECC), VA Boston Healthcare System, Boston, MA, USA.

We examined how serum cholesterol, an established risk factor for cerebrovascular disease (CVD), relates to cognitive function in healthy middle-older aged individuals with no neurologic or CVD history. A complete lipid panel was obtained from a cohort of one hundred twenty individuals, ages 43-85, who also underwent a comprehensive neuropsychological examination. In order to reduce the number of variables and empirically identify broad cognitive domains, scores from neuropsychological tests were submitted into a factor analysis. This analysis revealed three explainable factors: Memory, Executive Function and Memory/Language. Three separate hierarchical multiple regression analyses were conducted using individual cholesterol metrics (total cholesterol, low density lipoprotein; LDL, high density lipoprotein; HDL, and triglycerides), as well as age, education, medication status (lipid lowering agents), ApoE status, and additional risk factors for CVD to predict neuropsychological function. The Memory Factor was predicted by a combination of age, LDL, and triglyceride levels; both age and triglycerides were negatively associated with factor score, while LDL levels revealed a positive relationship. Both the Executive and Memory/Language factor were only explained by education, whereby more years were associated with better performance. These results provide evidence that individual cholesterol lipoproteins and triglycerides may differentially impact cognitive function, over and above other common CVD risk factors and ApoE status. Our findings demonstrate the importance of consideration of vascular risk factors, such as cholesterol, in studies of cognitive aging.
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http://dx.doi.org/10.1007/s11011-016-9797-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4913474PMC
April 2016

Posttraumatic Stress Disorder as a Catalyst for the Association Between Metabolic Syndrome and Reduced Cortical Thickness.

Biol Psychiatry 2016 09 8;80(5):363-71. Epub 2015 Dec 8.

National Center for PTSD, Boston, Massachusetts; Department of Psychiatry, Boston, Massachusetts; Biomedical Genetics, Boston University School of Medicine, Boston, Massachusetts.

Background: Metabolic syndrome (MetS), defined by a constellation of cardiometabolic pathologies, is highly prevalent among veterans, especially veterans with posttraumatic stress disorder (PTSD), and poses a major risk for adverse health outcomes, including neurodegeneration and mortality. Given this, we evaluated 1) the association between MetS and neural integrity, indexed by cortical thickness; 2) the relationship between PTSD and MetS; and 3) whether PTSD was associated with cortical thickness indirectly through MetS.

Methods: The sample consisted of 346 U.S. military veterans (89.3% male; 71.4% white) who deployed to Iraq, Afghanistan, or both. Neuroimaging data were available for 274 participants.

Results: In whole-brain analyses, MetS was negatively associated with cortical thickness in two left and four right hemisphere regions, as follows: bilateral temporal lobe, including temporal pole, fusiform gyrus, and insula, and extending into occipital cortex (left hemisphere) and orbitofrontal cortex (right hemisphere); bilateral precuneus, posterior cingulate, calcarine, and occipital-parietal cortex; and right rostral anterior cingulate cortex and central sulcus/postcentral gyrus. Path models showed that PTSD predicted MetS (β = .19, p < .001), which was associated with reduced cortical thickness (β = -.29 to -.43, all p < .001).

Conclusions: Results from this young veteran sample provide evidence that PTSD confers risk for cardiometabolic pathology and neurodegeneration and raise concern that this cohort may be aging prematurely and at risk for substantial medical and cognitive decline. This study highlights the need to identify the molecular mechanisms linking PTSD to MetS and effective interventions to reduce PTSD-related health comorbidities.
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http://dx.doi.org/10.1016/j.biopsych.2015.11.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4899313PMC
September 2016

Glucose Dysregulation Interacts With APOE-∊4 to Potentiate Temporoparietal Cortical Thinning.

Am J Alzheimers Dis Other Demen 2016 Feb 24;31(1):76-86. Epub 2015 May 24.

Department of Psychiatry, VA Boston Healthcare System, Boston, MA, USA Department of Psychiatry, Harvard Medical School, Boston, MA, USA.

We examined the interactive effects of apolipoprotein ∊4 (APOE-∊4), a risk factor for Alzheimer's disease (AD), and diabetes risk on cortical thickness among 107 healthy elderly participants; in particular, participants included 27 APOE-∊4+ and 80 APOE-∊4- controls using T1-weighted structural magnetic resonance imaging. Regions of interests included select frontal, temporal, and parietal cortical regions. Among APOE-∊4, glucose abnormalities independently predicted reduced cortical thickness among temporoparietal regions but failed to predict changes for noncarriers. However, among noncarriers, age independently predicted reduced cortical thickness among temporoparietal and frontal regions. Diabetes risk is particularly important for the integrity of cortical gray matter in APOE-∊4 and demonstrates a pattern of thinning that is expected in preclinical AD. However, in the absence of this genetic factor, age confers risk for reduced cortical thickness among regions of expected compromise. This study supports aggressive management of cerebrovascular factors and earlier preclinical detection of AD among individuals presenting with genetic and metabolic risks.
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http://dx.doi.org/10.1177/1533317515587084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4913470PMC
February 2016

Mild Cognitive Impairment is Associated With White Matter Integrity Changes in Late-Myelinating Regions Within the Corpus Callosum.

Am J Alzheimers Dis Other Demen 2016 Feb 22;31(1):68-75. Epub 2015 Apr 22.

Neuroimaging Research for Veterans Center, VA Boston Healthcare System, Boston, MA, USA Department of Medicine, Harvard Medical School, Boston, MA, USA.

Degenerative brain changes in Alzheimer's disease may occur in reverse order of normal brain development based on the retrogenesis model. This study tested whether evidence of reverse myelination was observed in mild cognitive impairment (MCI) using a data-driven analytic approach based on life span developmental data. Whole-brain high-resolution diffusion tensor imaging scans were obtained for 31 patients with MCI and 79 demographically matched healthy older adults. Comparisons across corpus callosum (CC) regions of interest (ROIs) showed decreased fractional anisotropy (FA) in the body but not in the genu or splenium; early-, middle-, and late-myelinating ROIs restricted to the CC revealed decreased FA in late- but not early- or middle-myelinating ROIs. Voxelwise group differences revealed areas of lower FA in MCI, but whole-brain differences were equally distributed across early-, middle-, and late-myelinating regions. Overall, results within the CC support the retrogenesis model, although caution is needed when generalizing these results beyond the CC.
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http://dx.doi.org/10.1177/1533317515578257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4913466PMC
February 2016

Widespread effects of alcohol on white matter microstructure.

Alcohol Clin Exp Res 2014 Dec 18;38(12):2925-33. Epub 2014 Nov 18.

Geriatric Research, Education and Clinical Center (GRECC), Translational Research Center for TBI and Stress Disorders (TRACTS), VA Boston Healthcare System, Boston, Massachusetts; Neuroimaging Research Center for Veterans, VA Boston Healthcare System, Boston, Massachusetts; Department of Psychiatry, Harvard Medical School, Boston, Massachusetts.

Background: Evidence suggests that chronic misuse of alcohol may preferentially affect the integrity of frontal white matter (WM) tracts, which can impact executive functions important to achieve and maintain abstinence.

Methods: Global and regional WM microstructure was assessed using diffusion magnetic resonance measures of fractional anisotropy (FA) for 31 abstinent alcoholics (ALC) with an average of 25 years of abuse and approximately 5 years of sobriety and 20 nonalcoholic control (NC) participants. Data processing was conducted with FreeSurfer and FSL processing streams. Voxelwise processing of the FA data was carried out using tract-based spatial statistics. Clusters of significance were created to provide a quantitative summary of highly significant regions within the voxelwise analysis.

Results: Widespread, bilateral reductions in FA were observed in ALC as compared to NC participants in multiple frontal, temporal, parietal, and cerebellar WM tracts. FA in the left inferior frontal gyrus was associated with drinking severity.

Conclusions: This study found widespread reductions in WM integrity in a group of ALC compared to NC participants, with most pronounced effects in frontal and superior tracts. Decreased FA throughout the frontostriatal circuits that mediate inhibitory control may result in impulsive behavior and inability to maintain sobriety.
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http://dx.doi.org/10.1111/acer.12568DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4293208PMC
December 2014

Reduced cortical thickness in veterans exposed to early life trauma.

Psychiatry Res 2014 Aug 2;223(2):53-60. Epub 2014 May 2.

Translational Research Center for TBI and Stress Disorders (TRACTS)/Geriatric Research Education and Clinical Centers (GRECC), VA Boston Healthcare System, Jamaica Plain, MA, USA; Department of Psychiatry, Harvard Medical School, Cambridge, MA, USA.

Studies have shown that early life trauma may influence neural development and increase the risk of developing psychological disorders in adulthood. We used magnetic resonance imaging to examine the impact of early life trauma on the relationship between current posttraumatic stress disorder (PTSD) symptoms and cortical thickness/subcortical volumes in a sample of deployed personnel from Operation Enduring Freedom/Operation Iraqi Freedom. A group of 108 service members enrolled in the Translational Research Center for Traumatic Brain Injury and Stress Disorders (TRACTS) were divided into those with interpersonal early life trauma (EL-Trauma+) and Control (without interpersonal early life trauma) groups based on the Traumatic Life Events Questionnaire. PTSD symptoms were assessed using the Clinician-Administered PTSD Scale. Cortical thickness and subcortical volumes were analyzed using the FreeSurfer image analysis package. Thickness of the paracentral and posterior cingulate regions was positively associated with PTSD severity in the EL-Trauma+ group and negatively in the Control group. In the EL-Trauma+ group, both the right amygdala and the left hippocampus were positively associated with PTSD severity. This study illustrates a possible influence of early life trauma on the vulnerability of specific brain regions to stress. Changes in neural morphometry may provide information about the emergence and maintenance of symptoms in individuals with PTSD.
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http://dx.doi.org/10.1016/j.pscychresns.2014.04.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4423392PMC
August 2014

Interactive effects of apolipoprotein E4 and diabetes risk on later myelinating white matter regions in neurologically healthy older aged adults.

Am J Alzheimers Dis Other Demen 2014 May 31;29(3):222-35. Epub 2013 Dec 31.

1Psychology Service, VA Boston Healthcare System, Boston, MA, USA.

Possession of the apolipoprotein E4 (APOE4) allele and diabetes risk are independently related to reduced white matter (WM) integrity that may contribute to the development of Alzheimer's disease (AD). The purpose of this study is to examine the interactive effects of APOE4 and diabetes risk on later myelinating WM regions among healthy elderly individuals at risk of AD. A sample of 107 healthy elderly (80 APOE4-/27 APOE4+) individuals underwent structural magnetic resonance imaging/diffusion tensor imaging (DTI). Data were prepared using Tract-Based Spatial Statistics, and a priori regions of interest (ROIs) were extracted from T1-based WM parcellations. Regions of interest included later myelinating frontal/temporal/parietal WM regions and control regions measured by fractional anisotropy (FA). There were no APOE group differences in DTI for any ROI. Within the APOE4 group, we found negative relationships between hemoglobin A1c/fasting glucose and APOE4 on FA for all later myelinating WM regions but not for early/middle myelinating control regions. Results also showed APOE4/diabetes risk interactions for WM underlying supramarginal, superior temporal, precuneus, superior parietal, and superior frontal regions. Results suggest interactive effects of APOE4 and diabetes risk on later myelinating WM regions, which supports preclinical detection of AD among this particularly susceptible subgroup.
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http://dx.doi.org/10.1177/1533317513517045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4356251PMC
May 2014

Reduced cortical thickness with increased lifetime burden of PTSD in OEF/OIF Veterans and the impact of comorbid TBI.

Neuroimage Clin 2013 22;2:601-11. Epub 2013 Apr 22.

Translational Research Center for TBI and Stress Disorders (TRACTS), VA Boston Healthcare System, USA.

Posttraumatic stress disorder (PTSD) and mild traumatic brain injury (mTBI) in military personnel is increasing dramatically following the OEF/OIF conflicts and is associated with alterations to brain structure. The present study examined the relationship between PTSD and cortical thickness, and its possible modification by mTBI, in a 104-subject OEF/OIF veteran cohort ranging in age from 20 to 62 years. For each participant, two T1-weighted scans were averaged to create high-resolution images for calculation of regional cortical thickness. PTSD symptoms were assessed using the Clinician Administered PTSD Scale (CAPS) and scores were derived based on the previous month's symptoms ("current") and a Cumulative Lifetime Burden of PTSD (CLB-P) reflecting the integral of CAPS scores across the lifetime. Mild TBI was diagnosed using the Boston Assessment of TBI-Lifetime (BAT-L). Results demonstrated a clear negative relationship between current PTSD severity and thickness in both postcentral gyri and middle temporal gyri. This relationship was stronger and more extensive when considering lifetime burden (CLB-P), demonstrating the importance of looking at trauma in the context of an individual's lifetime, rather than only at their current symptoms. Finally, interactions with current PTSD only and comorbid current PTSD and mTBI were found in several regions, implying an additive effect of lifetime PTSD and mTBI on cortical thickness.
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http://dx.doi.org/10.1016/j.nicl.2013.04.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3777819PMC
November 2013

Decreased white matter integrity in neuropsychologically defined mild cognitive impairment is independent of cortical thinning.

J Int Neuropsychol Soc 2013 Sep 1;19(8):925-37. Epub 2013 Jul 1.

Psychology Service, VA Boston Healthcare System, Boston, MA, USA.

Improved understanding of the pattern of white matter changes in early and prodromal Alzheimer’s disease (AD) states such as mild cognitive impairment (MCI) is necessary to support earlier preclinical detection of AD, and debate remains whether white matter changes in MCI are secondary to gray matter changes. We applied neuropsychologically based MCI criteria to a sample of normally aging older adults; 32 participants met criteria for MCI and 81 participants were classified as normal control (NC) subjects. Whole-head high resolution T1 and diffusion tensor imaging scans were completed. Tract-Based Spatial Statistics was applied and a priori selected regions of interest were extracted. Hippocampal volume and cortical thickness averaged across regions with known vulnerability to AD were derived. Controlling for corticalthic kness, the MCI group showed decreased average fractional anisotropy (FA) and decreased FA in parietal white matter and in white matter underlying the entorhinal and posterior cingulate cortices relative to the NC group. Statistically controlling for cortical thickness, medial temporal FA was related to memory and parietal FA was related to executive functioning. These results provide further support for the potential role of white matter integrity as an early biomarker for individuals at risk for AD and highlight that changes in white matter may be independent of gray matter changes.
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http://dx.doi.org/10.1017/S1355617713000660DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4356249PMC
September 2013

Associations between T1 white matter lesion volume and regional white matter microstructure in aging.

Hum Brain Mapp 2014 Mar 30;35(3):1085-100. Epub 2013 Jan 30.

Geriatric Research, Education and Clinical Center (GRECC) and Neuroimaging Research for Veterans Center (NeRVe), VA Boston Healthcare System, Boston, Massachusetts; Division of Aging, Brigham and Women's Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts; Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Boston, Massachusetts.

White matter lesions, typically manifesting as regions of signal intensity abnormality (WMSA) on MRI, increase in frequency with age. However, the role of this damage in cognitive decline and disease is still not clear, as lesion volume has only loosely been associated with clinical status. Diffusion tensor imaging (DTI) has been used to examine the quantitative microstructural integrity of white matter, and has applications in the examination of subtle changes to tissue that appear visually normal on conventional imaging. The primary goal of this study was to determine whether major macrostructural white matter damage, (total WMSA volume), is associated with microstructural integrity of normal appearing white matter, and if these macrostructural changes fully account for microstructural changes. Imaging was performed in 126 nondemented individuals, ages 43-85 years, with no history of cerebrovascular disease. Controlling for age, greater WMSA volume was associated with decreased fractional anisotropy (FA) in widespread brain regions. Patterns were similar for FA and radial diffusivity but in contrast, WMSA was associated with axial diffusivity in fewer areas. Age was associated with FA in several regions, and many of these effects remained even when controlling for WMSA volume, suggesting the etiology of WMSAs does not fully account for all age-associated white matter deterioration. These results provide evidence that WMSA volume is associated with the integrity of normal-appearing white matter. In addition, our results suggest that overt lesions may not account for the association of increasing age with decreased white matter tissue integrity.
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http://dx.doi.org/10.1002/hbm.22236DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4356252PMC
March 2014

Interindividual variation in serum cholesterol is associated with regional white matter tissue integrity in older adults.

Hum Brain Mapp 2013 Aug 22;34(8):1826-41. Epub 2012 Mar 22.

Neuroimaging Research for Veterans Center, VA Boston Healthcare System, Boston, Massachusetts, USA.

Prior research has demonstrated links among vascular health and the occurrence of stroke, mild cognitive decline, and dementia in older adults. However, little is known about whether normal variation in vascular indicators may be related to changes in neural tissue integrity. Even less is known about how the brain is affected by cholesterol levels in the normal to moderate risk range, leading up to overt disease pathology. This study examined associations between serum lipid levels and DTI indicators of white matter (WM) structural integrity in a sample of 125 generally healthy older adults aged 43-87 years. Whole-brain voxelwise analysis, controlling for age and gender, revealed low density lipoprotein levels (LDL) as the most robust correlate of regional WM structural integrity of the measured lipids. Higher LDL was associated with decreased WM integrity in right frontal and temporal regions, the superior longitudinal fasciculus and internal/external capsules. Increasing LDL was associated with increased radial and axial diffusivity; however, more widespread statistical effects were found for radial diffusivity. These findings suggest that normal interindividual variation in lipid levels is associated with compromised regional WM integrity, even in individuals below clinical thresholds for hyperlipidemia. Given the prevalence of cholesterol-associated sequelae in older adults, and mounting evidence suggesting a vascular role in the etiology of dementia, the current data suggest that understanding the relationship between cholesterol and brain tissue microstructure may have important clinical implications for early detection of vascular-related cognitive disorders and optimal regulation of serum lipids to maintain neural health in older adults.
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http://dx.doi.org/10.1002/hbm.22030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3707964PMC
August 2013

Distinct functional networks within the cerebellum and their relation to cortical systems assessed with independent component analysis.

Neuroimage 2012 May 9;60(4):2073-85. Epub 2012 Feb 9.

Neuroimaging Research Center for Veterans, VA Boston Healthcare System, Boston, MA, USA.

Cerebellar functional circuitry has been examined in several prior studies using resting fMRI data and seed-based procedures, as well as whole-brain independent component analysis (ICA). Here, we hypothesized that ICA applied to functional data from the cerebellum exclusively would provide increased sensitivity for detecting cerebellar networks compared to previous approaches. Consistency of group-level networks was assessed in two age- and sex-matched groups of twenty-five subjects each. Cerebellum-only ICA was compared to the traditional whole-brain ICA procedure to examine the potential gain in sensitivity of the novel method. In addition to replicating a number of previously identified cerebellar networks, the current approach revealed at least one network component that was not apparent with the application of whole brain ICA. These results demonstrate the gain in sensitivity attained through specifying the cerebellum as a target structure with regard to the identification of robust and reliable networks. The use of similar procedures could be important in further expanding on previously defined patterns of cerebellar functional anatomy, as well as provide information about unique networks that have not been explored in prior work. Such information may prove crucial for understanding the cognitive and behavioral importance of the cerebellum in health and disease.
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http://dx.doi.org/10.1016/j.neuroimage.2012.01.139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3549335PMC
May 2012

Cardiovascular Disease Risk Factors and Cognition in the Elderly.

Curr Cardiovasc Risk Rep 2011 Oct;5(5):407-412

Geriatric Research, Education and Clinical Center (GRECC).

While it is relatively widely known that cardiovascular disease (CVD) can result in cognitive decline, it is becoming increasingly clearer that actual risk factors for CVD, such as high blood pressure, diabetes, and obesity are also associated with alterations to brain structure and cognition. The prevalence of CVD risk factors increase exponentially with age and are often overlooked as a source of cognitive changes that are otherwise thought to be part of the 'normal' aging process. Associated cognitive changes are observed even at levels of risk that would be considered subclinical by current diagnostic convention, and are often significant enough to interfere with daily functional abilities. More importantly, if not controlled, CVD risk can lead to further decline, including cerebrovacsular disease and dementia. Thus, it is critically important to consider these factors in the elderly and we recommend more routine cognitive screenings, particularly when CVD risk factors are involved.
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http://dx.doi.org/10.1007/s12170-011-0189-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3245189PMC
October 2011

Association between white matter microstructure, executive functions, and processing speed in older adults: the impact of vascular health.

Hum Brain Mapp 2013 Jan 23;34(1):77-95. Epub 2011 Sep 23.

Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Alzheimer Center Limburg, University Maastricht, 6200 MD Maastricht, The Netherlands.

Cerebral white matter damage is not only a commonly reported consequence of healthy aging, but is also associated with cognitive decline and dementia. The aetiology of this damage is unclear; however, individuals with hypertension have a greater burden of white matter signal abnormalities (WMSA) on MR imaging than those without hypertension. It is therefore possible that elevated blood pressure (BP) impacts white matter tissue structure which in turn has a negative impact on cognition. However, little information exists about whether vascular health indexed by BP mediates the relationship between cognition and white matter tissue structure. We used diffusion tensor imaging to examine the impact of vascular health on regional associations between white matter integrity and cognition in healthy older adults spanning the normotensive to moderate-severe hypertensive BP range (43-87 years; N = 128). We examined how white matter structure was associated with performance on tests of two cognitive domains, executive functioning (EF) and processing speed (PS), and how patterns of regional associations were modified by BP and WMSA. Multiple linear regression and structural equation models demonstrated associations between tissue structure, EF and PS in frontal, temporal, parietal, and occipital white matter regions. Radial diffusivity was more prominently associated with performance than axial diffusivity. BP only minimally influenced the relationship between white matter integrity, EF and PS. However, WMSA volume had a major impact on neurocognitive associations. This suggests that, although BP and WMSA are causally related, these differential metrics of vascular health may act via independent pathways to influence brain structure, EF and PS.
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http://dx.doi.org/10.1002/hbm.21412DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3830829PMC
January 2013

Reduced cortical thickness in abstinent alcoholics and association with alcoholic behavior.

Alcohol Clin Exp Res 2011 Dec 15;35(12):2193-201. Epub 2011 Sep 15.

Geriatric Research Education and Clinical Center, VA Boston Healthcare System, Massachusetts, USA.

Background: Chronic misuse of alcohol results in widespread damage to the brain. Prior morphometric studies have examined cortical atrophy in individuals with alcoholism; however, no previous studies have examined alcohol-associated atrophy using cortical thickness measurements to obtain regional mapping of tissue loss across the full cortical surface.

Methods: We compared cortical thickness measures from 31 abstinent individuals with a history of prior alcohol abuse to 34 healthy nonalcoholic control participants (total sample size = 65). Cortical surface models were created from high-resolution T1-weighted images, and cortical thickness was then estimated as the distance between the gray matter/white matter boundary and the outer cortical surface.

Results: Abstinent alcoholics showed reduced whole-brain thickness as compared to nonalcoholic participants. Decreases in thickness were found bilaterally in (i) superior frontal, (ii) precentral, (iii) postcentral, (iv) middle frontal, (v) middle/superior temporal, (vi) middle temporal, and (vii) lateral occipital cortical regions. Decreased cortical thickness in the alcoholic group was associated with severity of alcohol abuse.

Conclusions: These findings demonstrate widespread reduction in cortical thickness as a consequence of chronic alcoholism, with most severe reductions in frontal and temporal brain regions.
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http://dx.doi.org/10.1111/j.1530-0277.2011.01576.xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3613762PMC
December 2011

Inter-individual variation in blood pressure is associated with regional white matter integrity in generally healthy older adults.

Neuroimage 2012 Jan 23;59(1):181-92. Epub 2011 Jul 23.

Neuroimaging Research for Veterans Center, VA Boston Healthcare System, Boston, MA, USA.

Prior studies have documented a range of brain changes that occur as a result of healthy aging as well as neural alterations due to profound dysregulation in vascular health such as extreme hypertension, cerebrovascular disease and stroke. In contrast, little information exists about the more transitionary state between the normal and abnormal physiology that contributes to vascular disease and cognitive decline. Specifically, little information exists with regard to the influence of systemic vascular physiology on brain tissue structure in older individuals with low risk for cerebrovascular disease and with no evidence of cognitive impairment. We examined the association between resting blood pressure and diffusion tensor imaging (DTI) indices of white matter microstructure in 128 healthy older adults (43-87 years) spanning the normotensive to moderate-severe hypertensive range. Mean arterial blood pressure (MABP) was related to diffusion measures in several regions of the brain with greatest associations in the anterior corpus callosum and lateral frontal, precentral, superior frontal, lateral parietal and precuneus white matter. Associations between white matter integrity and blood pressure remained when controlling for age, when controlling for white matter lesions, and when limiting the analyses to only normotensive, pharmacologically controlled and pre-hypertensive individuals. Of the diffusion measures examined, associations were strongest between MABP and radial diffusivity which may indicate that blood pressure has an influence on myelin structure. Associations between MABP and white matter integrity followed spatial patterns resembling those often attributed to the effects of chronological age, suggesting that systemic cerebrovascular health may play a role in neural tissue degeneration classically ascribed to aging. These results demonstrate the importance of the consideration of vascular physiology in studies of cognitive and neural aging, and that this significance extends to even the normotensive and medically controlled population. These data additionally suggest that optimal management of blood pressure may require consideration of the more subtle influence of vascular health on neural health in addition to the primary goal of prevention of a major cerebrovascular event.
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http://dx.doi.org/10.1016/j.neuroimage.2011.07.033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3209709PMC
January 2012

Thickness of the human cerebral cortex is associated with metrics of cerebrovascular health in a normative sample of community dwelling older adults.

Neuroimage 2011 Feb 28;54(4):2659-71. Epub 2010 Oct 28.

Geriatric Research, Education and Clinical Center (GRECC), VA Boston Healthcare System, Boston, MA 02130, USA.

We examined how wide ranges in levels of risk factors for cerebrovascular disease are associated with thickness of the human cerebral cortex in 115 individuals ages 43-83 with no cerebrovascular or neurologic history. Cerebrovascular risk factors included blood pressure, cholesterol, body mass index, creatinine, and diabetes-related factors. Variables were submitted into a principal components analysis that confirmed four orthogonal factors (blood pressure, cholesterol, cholesterol/metabolic and glucose). T1-weighted MRI was used to create models of the cortex for calculation of regional cortical thickness. Increasing blood pressure factor scores were associated with numerous regions of reduced thickness. Increasing glucose scores were modestly associated with areas of regionally decreased thickness. Increasing cholesterol scores, in contrast, were associated with thicker cortex across the whole brain. All findings were primarily independent of age. These results provide evidence that normal and moderately abnormal levels of parameters used to assess cerebrovascular health may impact brain structure, even in the absence of cerebrovascular disease. Our data have important implications for the clinical management of vascular health, as well as for what is currently conceptualized as "normal aging" as they suggest that subclinical levels of risk may impact cortical gray matter before a disease process is evident.
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http://dx.doi.org/10.1016/j.neuroimage.2010.10.050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3026290PMC
February 2011

Variation in blood pressure is associated with white matter microstructure but not cognition in African Americans.

Neuropsychology 2010 Mar;24(2):199-208

VA Boston Healthcare System and Brigham, & Women's Hospital.

Although hypertension is a major risk factor for cerebrovascular disease (CVD) and is highly prevalent in African Americans, little is known about how blood pressure (BP) affects brain-behavior relationships in this population. In predominantly Caucasian populations, high BP is associated with alterations in frontal-subcortical white matter and in executive functioning aspects of cognition. We investigated associations among BP, brain structure, and neuropsychological functioning in 52 middle-older-age African Americans without diagnosed history of CVD. All participants underwent diffusion tensor imaging for examination of white matter integrity, indexed by fractional anisotropy (FA). Three regions of interest were derived in the anterior (genu) and posterior (splenium) corpus callosum and across the whole brain. A brief neuropsychological battery was administered from which composite scores of executive function and memory were derived. Blood pressure was characterized by mean arterial blood pressure (MABP). When controlling for age, higher MABP was associated with lower FA in the genu, and there was a trend for this same relationship with regard to whole-brain FA. When the sample was broken into groups on the basis of treatment for BP regulation (medicated vs. nonmedicated), MABP was related to genu and whole-brain FA only in the nonmedicated group. Neither MABP nor FA was significantly related to either neuropsychological composite score regardless of medication use. These data provide important evidence that variation in BP may contribute to significant alterations in specific neural regions of white matter in nonmedicated individuals without symptoms of overt CVD.
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http://dx.doi.org/10.1037/a0018108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2849283PMC
March 2010
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