Peripheral apoE isoform levels in cognitively normal APOE ε3/ε4 individuals are associated with regional gray matter volume and cerebral glucose metabolism

Abstract Background White matter hyperintensities (WMH) are frequently found in Alzheimer’s disease (AD). Commonly considered as a marker of cerebrovascular disease, regional WMH may be related to pathological hallmarks of AD, including beta-amyloid (Aβ) plaques and neurodegeneration. The aim of this study was to examine the regional distribution of WMH associated with Aβ burden, glucose hypometabolism, and gray matter volume reduction. Methods In a total of 155 participants (IMAP+ cohort) across the cognitive continuum from normal cognition to AD dementia, FLAIR MRI, AV45-PET, FDG-PET, and T1 MRI were acquired. WMH were automatically segmented from FLAIR images. Mean levels of neocortical Aβ deposition (AV45-PET), temporo-parietal glucose metabolism (FDG-PET), and medial-temporal gray matter volume (GMV) were extracted from processed images using established AD meta-signature templates. Associations between AD brain biomarkers and WMH, as assessed in region-of-interest and voxel-wise, were examined, adjusting for age, sex, education, and systolic blood pressure. Results There were no significant associations between global Aβ burden and region-specific WMH. Voxel-wise WMH in the splenium of the corpus callosum correlated with greater Aβ deposition at a more liberal threshold. Region- and voxel-based WMH in the posterior corpus callosum, along with parietal, occipital, and frontal areas, were associated with lower temporo-parietal glucose metabolism. Similarly, lower medial-temporal GMV correlated with WMH in the posterior corpus callosum in addition to parietal, occipital, and fontal areas. Conclusions This study demonstrates that local white matter damage is correlated with multimodal brain biomarkers of AD. Our results highlight modality-specific topographic patterns of WMH, which converged in the posterior white matter. Overall, these cross-sectional findings corroborate associations of regional WMH with AD-typical Aß deposition and neurodegeneration.

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Voxel-based correlation of 18F-THK5351 accumulation and gray matter volume in the brain of cognitively normal older adults

EJNMMI Research ◽

10.1186/s13550-019-0552-3 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 2

Author(s):

Yoko Shigemoto ◽

Daichi Sone ◽

Miho Ota ◽

Norihide Maikusa ◽

Masayo Ogawa ◽

...

Keyword(s):

Older Adults ◽

Gray Matter ◽

Gray Matter Volume ◽

Cognitively Normal ◽

Matter Volume ◽

The Brain

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What factors explain racial differences in memory‐related gray matter volume regions of interest among cognitively normal older adults?

Alzheimer s & Dementia ◽

10.1002/alz.047637 ◽

2020 ◽

Vol 16 (S10) ◽

Author(s):

Sara L Godina ◽

Caterina Rosano ◽

Peter Gianaros ◽

Howard J Aizenstein ◽

Michelle C Carlson ◽

...

Keyword(s):

Older Adults ◽

Racial Differences ◽

Gray Matter ◽

Gray Matter Volume ◽

Regions Of Interest ◽

Cognitively Normal ◽

Matter Volume

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REGION-SPECIFIC ATROPHY AS MEASURED BY CORTICAL GRAY MATTER VOLUME IS ASSOCIATED WITH BOTH REGIONAL AND TOTAL CORTICAL AMYLOID-BETA BURDEN IN COGNITIVELY NORMAL INDIVIDUALS AT RISK FOR ALZHEIMER'S DISEASE

American Journal of Geriatric Psychiatry ◽

10.1016/j.jagp.2019.01.100 ◽

2019 ◽

Vol 27 (3) ◽

pp. S186-S187

Author(s):

Ryan O'Dell ◽

Manan Gupta ◽

Joel Gelernter ◽

Richard Carson ◽

Christopher van Dyck ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

At Risk ◽

Amyloid Beta ◽

Gray Matter ◽

Gray Matter Volume ◽

Cognitively Normal ◽

Matter Volume ◽

Normal Individuals ◽

Cortical Gray Matter

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White matter lesions and brain gray matter volume in cognitively normal elders

Neurobiology of Aging ◽

10.1016/j.neurobiolaging.2011.08.010 ◽

2012 ◽

Vol 33 (4) ◽

pp. 834.e7-834.e16 ◽

Cited By ~ 64

Author(s):

Cyrus A. Raji ◽

Oscar L. Lopez ◽

Lewis H. Kuller ◽

Owen T. Carmichael ◽

William T. Longstreth ◽

...

Keyword(s):

White Matter ◽

Gray Matter ◽

Gray Matter Volume ◽

White Matter Lesions ◽

Cognitively Normal ◽

Matter Volume

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Regional Gray Matter Volume Identifies High Risk of Unsafe Driving in Healthy Older People

Frontiers in Aging Neuroscience ◽

10.3389/fnagi.2020.592979 ◽

2020 ◽

Vol 12 ◽

Author(s):

Yasuharu Yamamoto ◽

Bun Yamagata ◽

Jinichi Hirano ◽

Ryo Ueda ◽

Hiroshi Yoshitake ◽

...

Keyword(s):

Gray Matter ◽

Traffic Accidents ◽

Gray Matter Volume ◽

Older Drivers ◽

Driving Ability ◽

Neural Basis ◽

Cognitively Normal ◽

Matter Volume ◽

Cortical Regions ◽

The Right

In developed countries, the number of traffic accidents caused by older drivers is increasing. Approximately half of the older drivers who cause fatal accidents are cognitively normal. Thus, it is important to identify older drivers who are cognitively normal but at high risk of causing fatal traffic accidents. However, no standardized method for assessing the driving ability of older drivers has been established. We aimed to establish an objective assessment of driving ability and to clarify the neural basis of unsafe driving in healthy older people. We enrolled 32 healthy older individuals aged over 65 years and classified unsafe drivers using an on-road driving test. We then utilized a machine learning approach to distinguish unsafe drivers from safe drivers based on clinical features and gray matter volume data. Twenty-one participants were classified as safe drivers and 11 participants as unsafe drivers. A linear support vector machine classifier successfully distinguished unsafe drivers from safe drivers with 87.5% accuracy (sensitivity of 63.6% and specificity of 100%). Five parameters (age and gray matter volume in four cortical regions, including the left superior part of the precentral sulcus, the left sulcus intermedius primus [of Jensen], the right orbital part of the inferior frontal gyrus, and the right superior frontal sulcus), were consistently selected as features for the final classification model. Our findings indicate that the cortical regions implicated in voluntary orienting of attention, decision making, and working memory may constitute the essential neural basis of driving behavior.

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Cortisol associated with hypometabolism across the Alzheimer’s disease spectrum

10.1101/514968 ◽

2019 ◽

Author(s):

Miranka Wirth ◽

Catharina Lange ◽

Willem Huijbers ◽

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Glucose Metabolism ◽

Gray Matter ◽

Plasma Cortisol ◽

Gray Matter Volume ◽

Brain Glucose ◽

Brain Glucose Metabolism ◽

Matter Volume ◽

Neuroimaging Biomarkers

AbstractObjectiveHypothalamic-pituitary-adrenal (HPA) dysregulation is proposed as a risk factor for Alzheimer’s disease (AD). This cross-sectional study assessed relationships between plasma cortisol levels and neuroimaging biomarkers, specifically brain glucose metabolism and gray matter volume, across the AD spectrum.MethodsCognitively normal older adults and patients with mild cognitive impairment (MCI) and AD dementia were included from the Alzheimer’s Disease Neuroimaging Initiative. Participants (n = 556) were selected based on availability of baseline measures of plasma cortisol levels and gray matter volume, as estimated with magnetic resonance imaging. Within a subsample (n = 288), we examined brain glucose metabolism (n = 288) as with positron emission tomography. Relationships between plasma cortisol and AD neuroimaging biomarkers were assessed using regions-of-interest and voxel-wise analyses.ResultsAcross the entire cohort, higher plasma cortisol was also related to lower gray matter volume, most notably in the left lateral temporal-parietal-occipital regions. Importantly, higher plasma cortisol concentration was also related to hypometabolism, especially in lateral temporo-parietal and medial parietal regions. When stratified by diagnosis, these negative associations were most pronounced in MCI and AD patients.InterpretationHigh plasma cortisol was associated with hypometabolism predominantly in AD-sensitive regions. Our results indicate that HPA axis activation could influence brain metabolism and exacerbate existing AD pathological processes. This is consistent with a notion that stress is a conceivable target for intervention to slow down AD progression. Future studies should delineate underlying pathological mechanisms and investigate if clinical or lifestyle interventions could alleviate negative actions of stress on AD.

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