%0 Journal Article %J J Alzheimers Dis %D 2022 %T Association of Carotid Intima Media Thickening with Future Brain Region Specific Amyloid-β Burden. %A Baradaran, Hediyeh %A Peloso, Gina M %A Polak, Joseph F %A Killiany, Ronald J %A Ghosh, Saptaparni %A DeCarli, Charles S %A Thibault, Emma G %A Sperling, Reisa A %A Johnson, Keith A %A Beiser, Alexa %A Romero, Jose R %A Seshadri, Sudha %X

BACKGROUND: Carotid atherosclerosis is associated with cognitive impairment and dementia, though there is limited evidence of a direct link between carotid disease and amyloid-β (Aβ) burden.

OBJECTIVE: We studied the association of baseline and progressive carotid intima media thickness (CIMT) with Aβ on 11C-Pittsburgh Compound B (PiB) to determine if those with carotid atherosclerosis would have higher Aβ burden.

METHODS: We studied 47 participants from the Framingham Offspring cohort with carotid ultrasounds measuring CIMT at their 6th clinic examination (aged 49.5±5.7 years) and an average of 9.6 years later, and PiB imaging measuring Aβ on average 22.1 years post baseline. We used multivariate linear regression analyses to relate baseline, follow-up, mean, and progression of internal carotid artery (ICA) and common carotid artery (CCA) CIMT to Aβ in brain regions associated with Alzheimer's disease (AD) and related dementias (ADRD), adjusting for age, sex, and other vascular risk factors.

RESULTS: Participants with higher mean ICA IMT had more Aβ in the precuneus (beta±standard error [β±SE]: 0.466±0.171 mm, p = 0.01) and the frontal, lateral, and retrosplenial regions (β±SE: 0.392±0.164 mm, p = 0.022) after adjusting for age, sex, vascular risk factors, and medication use. We did not find an association between any CCA IMT measures and Aβ or progression of ICA or CCA IMT and Aβ.

CONCLUSION: Carotid atherosclerosis, as measured by ICA IMT, is associated with increased Aβ burden later in life. These findings support a link between vascular disease and AD/ADRD pathophysiology.

%B J Alzheimers Dis %V 89 %P 223-232 %8 2022 Aug 30 %G eng %N 1 %R 10.3233/JAD-215679 %0 Journal Article %J J Alzheimers Dis %D 2018 %T Genetic Interaction with Plasma Lipids on Alzheimer's Disease in the Framingham Heart Study. %A Peloso, Gina M %A Beiser, Alexa S %A DeStefano, Anita L %A Seshadri, Sudha %X

Epidemiological and genetic studies have pointed to the role of cholesterol in Alzheimer's disease (AD). We explored the interaction of a genetic risk score (GRS) of AD risk alleles with mid-life plasma lipid levels (LDL-C, HDL-C, and triglycerides) on risk for AD in the Framingham Heart Study (FHS). Mid-life (between the ages of 40-60 years old) lipid levels were obtained from individuals in the FHS Original and Offspring cohorts (157 cases and 2,882 controls) with genetic data and AD status available. Cox proportional hazards regression was performed to test the interaction between mid-life lipid levels and an AD GRS, as well as the individual contributing SNPs, on risk of incident AD adjusting for age, sex, and cohort. We found a significant interaction between a GRS of AD loci and log triglyceride levels on risk of clinical AD (p = 0.006), but no interaction of the GRS with HDL-C (p = 0.458) or LDL-C (p = 0.366). We then tested the interaction between the individual SNPs contributing to the GRS and log triglycerides. We found two SNPs that had interactions with triglycerides on AD risk that reached a p-value < 0.05 (rs11218343 and APOEɛ4). The association between some AD SNPs and risk of AD may be modified by triglyceride levels. Furthermore, sequential testing of a GRS with a set of traits on disease followed by testing individual SNPs for interaction provides a framework for narrowing the associations that need to be tested for interaction analyses. Replication is needed to confirm these findings.

%B J Alzheimers Dis %V 66 %P 1275-1282 %8 2018 %G eng %N 3 %1 http://www.ncbi.nlm.nih.gov/pubmed/30412497?dopt=Abstract %R 10.3233/JAD-180751