Mid-life and late-life vascular risk factor burden and neuropathology in old age.

Alexa Beiser,Mekala R Raman,Thor D Stein,Jayandra J Himali,Claudia L Satizabal,Jamie M Walker,Ann C Mckee,Sarah C Conner,Herman Carneiro,Sudha Seshadri,Matthew P Pase,Victor E Alvarez

doi:10.1002/acn3.50936

Abstract

ObjectiveTo determine whether vascular risk factor burden in mid‐ or late‐life associates with postmortem vascular and neurodegenerative pathologies in a community‐based sample.MethodsWe studied participants from the Framingham Heart Study who participated in our voluntary brain bank program. Overall vascular risk factor burden was calculated using the Framingham Stroke Risk Profile (FSRP). Mid‐life FSRP was measured at 50 to 60 years of age. Following death, brains were autopsied and semi‐quantitatively assessed by board‐certified neuropathologists for cerebrovascular outcomes (cortical infarcts, subcortical infarcts, atherosclerosis, arteriosclerosis) and Alzheimer’s disease pathology (Braak stage, cerebral amyloid angiopathy, and neuritic plaque score). We estimated adjusted odds ratios between vascular risk burden (at mid‐life and before death) and neuropathological outcomes using logistic and proportional‐odds logistic models.ResultsThe median time interval between FSRP and death was 33.4 years for mid‐life FSRP and 4.4 years for final FSRP measurement before death. Higher mid‐life vascular risk burden was associated with increased odds of all cerebrovascular pathology, even with adjustment for vascular risk burden before death. Late‐life vascular risk burden was associated with increased odds of cortical infarcts (OR [95% CI]: 1.04 [1.00, 1.08]) and arteriosclerosis stage (OR [95% CI]: 1.03 [1.00, 1.05]). Mid‐life vascular risk burden was not associated with Alzheimer’s disease pathology, though late‐life vascular risk burden was associated with increased odds of higher Braak stage (OR [95% CI]: 1.03 [1.01, 1.05]).InterpretationMid‐life vascular risk burden was predictive of cerebrovascular but not Alzheimer’s disease neuropathology, even after adjustment for vascular risk factors before death.

Highlights

Growing evidence points to mid-life as a critical period by which vascular risk factors most strongly associate with brain health into old age
In the Framingham Heart Study (FHS), we recently showed that the association between higher vascular risk factor burden and lower brain volume was strongest when vascular risk factors were measured at younger ages.[1]
We examined the relationship of mid- and late-life vascular risk factor burden with neuropathology in old age in a well-characterized community-based cohort

Summary

Introduction

Growing evidence points to mid-life as a critical period by which vascular risk factors most strongly associate with brain health into old age. In the FHS, mid-life hypertension more strongly associates with late-life dementia risk as compared to late-life hypertension.[2] the Whitehall II study showed that high systolic blood pressure at age 50, but not 60 or 70, predicted a higher risk of late-life dementia.[3] these former studies focusing on clinical diagnosis or global brain volumes do not shed light on the underlying pathology. Mid-life vascular risk factors may increase the risk of late-life brain atrophy and clinical Alzheimer’s disease (AD) by causing cerebrovascular disease, AD, or a combination of the two. Clarifying the relationship between mid-life vascular risk and late-life neuropathology is important for elucidating the mechanisms leading to both AD and vascular cognitive impairment

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Conclusion