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APOE genotypes as a risk factor for age-dependent accumulation of cerebrovascular disease in older adults.

ABSTRACT: INTRODUCTION:Apolipoprotein E (APOE) is a susceptibility gene for late-onset Alzheimer's disease neuropathology; less is known about the relationship between APOE and cerebrovascular disease (CVD) neuropathology. METHODS:We investigated associations of APOE status with arteriolosclerosis, macroinfarcts and microinfarcts, and atherosclerosis in 1383 adults (65.9-108.2 years at death) with and without dementia. Excluding ?2/?4 carriers, multivariable regressions for each CVD-related neuropathology compared ?4 and ?2 carriers to ?3/?3 carriers adjusting for confounders including age and Alzheimer's neuropathology. RESULTS:Three hundred forty-two individuals (24.7%; ?87.7 years at death; 39.9% nondemented) were ?3/?4 or ?4/?4, and 180 (13.0%; ?89.9 years at death; 66.6% nondemented) were ?2/?3 or ?2/?2. ?4 carriers had higher odds of macroinfarcts (odds ratio = 1.41, 95% confidence interval: 1.02-1.94, P = .03), whereas ?2 carriers had higher odds of moderate-to-severe arteriolosclerosis (odds ratio = 1.68, 95% confidence interval: 1.15-2.45, P = .006) compared to ?3/?3 carriers. Age-stratified analyses suggested that these relationships were driven by ?4 carriers <90 years at death and ?2 carriers ?90 years at death, respectively. DISCUSSION:APOE differentially affects type and timing of CVD-related neuropathology.

SUBMITTER: Lamar M

PROVIDER: S-EPMC6368888 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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APOE genotypes as a risk factor for age-dependent accumulation of cerebrovascular disease in older adults.

Lamar Melissa M Yu Lei L Rubin Leah H LH James Bryan D BD Barnes Lisa L LL Farfel Jose Marcelo JM Gaiteri Chris C Buchman Aron S AS Bennett David A DA Schneider Julie A JA

Alzheimer's & dementia : the journal of the Alzheimer's Association 20181012 2

<h4>Introduction</h4>Apolipoprotein E (APOE) is a susceptibility gene for late-onset Alzheimer's disease neuropathology; less is known about the relationship between APOE and cerebrovascular disease (CVD) neuropathology.<h4>Methods</h4>We investigated associations of APOE status with arteriolosclerosis, macroinfarcts and microinfarcts, and atherosclerosis in 1383 adults (65.9-108.2 years at death) with and without dementia. Excluding ε2/ε4 carriers, multivariable regressions for each CVD-related ...[more]

PMID: 30321502

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Project description:Cerebral blood flow (CBF) becomes pulsatile in response to the pulsatile change in perfusion pressure that is regulated by cerebrovascular impedance. In this study, we aimed to characterize age-related differences in cerebrovascular impedance across the adult lifespan. Carotid artery pressure [(CAP), via applanation tonometry] and CBF velocity (CBFV) in the middle cerebral artery (via transcranial Doppler) were measured in 148 healthy adults (21-79 yr, 62% women). Cerebrovascular impedance was quantified using transfer function analysis. Coherence between changes in CBFV and CAP was >0.90 in the frequency range of 0.78-2.73 Hz, suggesting a linear dynamic relationship between these two variables. Impedance modulus at the first harmonics (0.78-1.56 Hz) of CBFV and CAP oscillations (Z1), reflecting mainly heart rate frequency, was 20% higher in the old (>64 yr, P = 0.002) and 13% higher in the middle-aged (45-64 yr, P = 0.08) than in young individuals (<45 yr). In addition, Z1 was 24% higher in men than in women (P < 0.001). Multiple linear regression analysis revealed that Z1 is negatively associated with systolic (β = -0.470), diastolic (β = -0.418), pulsatile (β = -0.374), and mean CBFV (β = -0.473; P < 0.001 for all) after adjustment for age, sex, and body mass index (BMI). These results suggest that older age and male sex are associated with higher cerebrovascular impedance than young individuals, which may contribute to brain hypoperfusion.NEW & NOTEWORTHY Impedance modulus at the first harmonics of cerebral blood flow velocity (CBFV) and carotid artery pressure oscillations (Z1) was higher in the old (>64 yr) than in the young individuals (<45 yr), and it was higher in men than in women. Z1 is negatively associated with CBFV after adjustment for age, sex, and body mass index. Increases in cerebrovascular impedance with age may buffer systemic arterial pressure fluctuations at the cost of increased brain hypoperfusion risk.

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APOE genotypes as a risk factor for age-dependent accumulation of cerebrovascular disease in older adults.

Publications

APOE genotypes as a risk factor for age-dependent accumulation of cerebrovascular disease in older adults.

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