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

Objective To determine whether vascular risk factor burden in mid‐ or late‐life associates with postmortem vascular and neurodegenerative pathologies in a community‐based sample. Methods We studied participants from the Framingham Heart Study who participated in our voluntary brain bank program. Ove...

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Vydáno v:Annals of clinical and translational neurology Ročník 6; číslo 12; s. 2403 - 2412
Hlavní autoři: Conner, Sarah C., Pase, Matthew P., Carneiro, Herman, Raman, Mekala R., McKee, Ann C., Alvarez, Victor E., Walker, Jamie M., Satizabal, Claudia L., Himali, Jayandra J., Stein, Thor D., Beiser, Alexa, Seshadri, Sudha
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States John Wiley & Sons, Inc 01.12.2019
John Wiley and Sons Inc
Wiley
Témata:
Age
Aged
Aged, 80 and over
Alzheimer Disease - epidemiology
Alzheimer Disease - pathology
Alzheimer's disease
Arteriosclerosis
Atherosclerosis
Blood pressure
Brain
Cardiac arrhythmia
Cardiovascular disease
Cerebrovascular Disorders - epidemiology
Cerebrovascular Disorders - pathology
Dementia
Diabetes
Donations
Female
Gender
Humans
Hypertension
Longitudinal Studies
Male
Massachusetts - epidemiology
Middle Aged
Neuropathology
Pathology
Prognosis
Risk Factors
Standard deviation
Tissue Banks
Massachusetts
ISSN:2328-9503, 2328-9503
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Shrnutí:Objective To determine whether vascular risk factor burden in mid‐ or late‐life associates with postmortem vascular and neurodegenerative pathologies in a community‐based sample. Methods We 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. Results The 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]). Interpretation Mid‐life vascular risk burden was predictive of cerebrovascular but not Alzheimer’s disease neuropathology, even after adjustment for vascular risk factors before death.
Bibliografie:Funding information
Ms. Conner reports funding from the National Institute of General Medical Sciences (NIGMS) Interdisciplinary Training Grant for Biostatisticians (T32GM74905‐14) and the National Heart, Lung, and Blood Institute (NHLBI) (F31HL145904‐01). Dr. Raman reports funding from NHLBI (T32HL125232‐01A1). Dr. Satizabal is supported by the Alzheimer’s Association (AARGD‐16‐443384). Dr. Pase is funded by a National Heart Foundation of Australia Future Leader Fellowship (ID, 102052). This study was also supported by grants from the National Institute on Aging (R01 AG054076, R01 AG049607, R01 AG033193, U01 AG049505, U01 AG052409, RF1 AG054156) and the National Institute of Neurological Disorders and Stroke (NS017950 and UH2 NS100605), and the NHLBI contract for the Framingham Heart Study (contract no. N01‐HC‐25195, HHSN268201500001I, and 75N92019D00031).
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ISSN:2328-9503
2328-9503
DOI:10.1002/acn3.50936