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Angiotensin II Blood Levels Are Associated with Smaller Hippocampal and Cortical Volumes in Cognitively Normal Older Adults.

ABSTRACT: BACKGROUND:There is emerging evidence about possible involvement of the renin-angiotensin system (RAS) in the pathogenesis of Alzheimer's disease (AD) and decline of cognitive function. However, little is known about associations with brain biomarkers. OBJECTIVE:Our study aimed to examine associations between blood ACE-1 and ANG II levels and brain MRI based volumes in non-demented participants, and whether these associations were mediated by blood pressure. METHODS:This cross-sectional study was conducted in 34 older participants from the Baltimore Experience Corps Trial (BECT) Brain Health Sub-study (BHS). Blood ANGII and ACE-1 levels were measured by ELISA and brain MRI volumes were generated using FreeSurfer 6.0. Multiple linear regression analysis, adjusting for intracranial volume and confounders, was used to determine associations between log transformed ANGII and ACE-1 levels and MRI volumes (mm3). RESULTS:Participants were predominantly female (76%), African-American (94%), with mean age of 66.9 and education of 14.4 years. In the fully adjusted model we observed significant inverse associations between log ANGII levels and total grey matter (?=Angiotensin II associated with smaller hippocampus14,935.50, ±7,444.83, p?=?0.05), total hippocampus (?=-129.97, ±105.27, p?=?0.03), rostral middle frontal (?=?-1580.40, ±584.74, p?=?0.02), and supramarginal parietal (?=?-978.90, ±365.54, p?=?0.02) volumes. There were no associations between ANGII levels and total white matter or entorhinal cortex volumes, or ACE-1 levels and any brain volumes. CONCLUSION:We observed that increased blood ANGII levels were associated with lower total grey matter, hippocampal, rostral middle frontal, and supramarginal parietal volumes, which are associated with cognitive domains that decline in preclinical AD.

SUBMITTER: Yasar S

PROVIDER: S-EPMC7293768 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Angiotensin II Blood Levels Are Associated with Smaller Hippocampal and Cortical Volumes in Cognitively Normal Older Adults.

Yasar Sevil S Moored Kyle D KD Adam Atif A Zabel Fiona F Chuang Yi-Fang YF Varma Vijay R VR Carlson Michelle C MC

Journal of Alzheimer's disease : JAD 20200101 2

<h4>Background</h4>There is emerging evidence about possible involvement of the renin-angiotensin system (RAS) in the pathogenesis of Alzheimer's disease (AD) and decline of cognitive function. However, little is known about associations with brain biomarkers.<h4>Objective</h4>Our study aimed to examine associations between blood ACE-1 and ANG II levels and brain MRI based volumes in non-demented participants, and whether these associations were mediated by blood pressure.<h4>Methods</h4>This cr ...[more]

PMID: 32280103

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Project description:Importance:Emotional and behavioral symptoms in cognitively normal older people may be direct manifestations of Alzheimer disease (AD) pathophysiology at the preclinical stage, prior to the onset of mild cognitive impairment. Loneliness is a perceived state of social and emotional isolation that has been associated with cognitive and functional decline and an increased risk of incident AD dementia. We hypothesized that loneliness might occur in association with elevated cortical amyloid burden, an in vivo research biomarker of AD. Objective:To determine whether cortical amyloid burden is associated with greater loneliness in cognitively normal older adults. Design, Setting, and Participants:Cross-sectional analyses using data from the Harvard Aging Brain Study of 79 cognitively normal, community-dwelling participants. A continuous, aggregate measure of cortical amyloid burden, determined by Pittsburgh Compound B-positron emission tomography (PiB-PET), was examined in association with loneliness in linear regression models adjusting for age, sex, apolipoprotein E ?4 (APOE?4), socioeconomic status, depression, anxiety, and social network (without and with the interaction of amyloid and APOE?4). We also quantified the association of high amyloid burden (amyloid-positive group) to loneliness (lonely group) using logistic regression, controlling for the same covariates, with the amyloid-positive group and the lonely group, each composing 32% of the sample (n?=?25). Main Outcomes and Measures:Loneliness, as determined by the 3-item UCLA Loneliness Scale (possible range, 3-12, with higher score indicating greater loneliness). Results:The 79 participants included 43 women and 36 men with a mean (SD) age of 76.4 (6.2) years. Mean (SD) cortical amyloid burden via PiB-PET was 1.230 (0.209), and the mean (SD) UCLA-3 loneliness score was 5.3 (1.8). Twenty-two (28%) had positive APOE?4 carrier status, and 25 (32%) were in the amyloid-positive group with cortical PiB distribution volume ratio greater than 1.2. Controlling for age, sex, APOE?4, socioeconomic status, depression, anxiety, and social network, we found that higher amyloid burden was significantly associated with greater loneliness: compared with individuals in the amyloid-negative group, those in the amyloid-positive group were 7.5-fold (95% CI, 1.7-fold to 34.0-fold) more likely to be classified as lonely than nonlonely (??=?3.3, partial r?=?0.4, P?=?.002). Furthermore, the association of high amyloid burden and loneliness was stronger in APOE?4 carriers than in noncarriers. Conclusions and Relevance:We report a novel association of loneliness with cortical amyloid burden in cognitively normal older adults, suggesting that loneliness is a neuropsychiatric symptom relevant to preclinical AD. This work will inform new research into the neural underpinnings and disease mechanisms involved in loneliness and may enhance early detection and intervention research in AD.

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Angiotensin II Blood Levels Are Associated with Smaller Hippocampal and Cortical Volumes in Cognitively Normal Older Adults.

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Angiotensin II Blood Levels Are Associated with Smaller Hippocampal and Cortical Volumes in Cognitively Normal Older Adults.

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