Alzheimer's Disease More Associated With Vascular Risk Factors in Mid-Life Than Later Life

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The cumulative effect of vascular risk factors had the most significant impact on development of amyloid plaques.
The cumulative effect of vascular risk factors had the most significant impact on development of amyloid plaques.

Development of amyloid plaques in the brain characteristic of Alzheimer's disease (AD) is more likely to be associated with vascular risk factors in midlife than with those accumulated in later years. The results of the Atherosclerosis Risk in Communities (ARIC)–Positron Emission Tomography (PET) Amyloid Imaging Study were published in the Journal of the American Medical Association.1

The ARIC-PET study (conducted alongside the ARIC Neurocognitive Study and the main ARIC Study), led by Rebecca Gottesman, MD, PhD, of Johns Hopkins University in Baltimore, Maryland, prospectively evaluated a cohort of 322 participants from the main ARIC study who did not have dementia for the influence of midlife vascular risk factors on amyloid deposits recorded an average of 23 years later on PET scan.

The ARIC study participants completed a series of 4 inpatient health evaluations starting in 1987 and ending in 2011, followed by a fifth visit for magnetic resonance imaging (MRI) and PET scans between 2011 and 2013. All the patients selected had available histories of the most established risk factors for heart disease, including diabetes, hypertension, hypercholesterolemia, and smoking.2-8 Additionally, the investigators included body mass index (BMI) in the evaluation.

The cumulative effect of risk factors had the most significant impact. A history of 2 or more vascular risk factors assessed at baseline in the ARIC study (age 45 to 64, mean 52) was associated with a significantly higher rate of amyloid deposits on PET scans taken at the last visit (when patients were mean age 76), compared with the absence of risk factors (61.2% vs 30.8%, respectively). At the same time, the appearance of 2 or more risk factors late in life was not associated with amyloid brain deposition (odds ratio (OR) 1.66; 95% CI, 0.75-3.69). Each additional risk factor represented an increased risk of amyloid deposits (OR 1.41; 95% CI, 1.09-1.83), compared with no risk factors.

From midlife to later life, rates of hypertension and diabetes increased in the cohort, while smoking and cholesterol levels decreased, although none of these factors, with the exception of BMI, were significant independent risk factors for amyloid deposits.

“We didn't look specifically at duration of these risk factors, but one possible explanation for the finding with midlife and not with late-life vascular risk factors is that people who had these risk factors in midlife may have been exposed to the risk factors for a longer period of time,” Dr Gottesman told Neurology Advisor. “Another explanation is that there is a key window when people are most vulnerable to the effects of elevated vascular risk,” she added.

Asked if reducing risk factors (such as managed diabetes or reduced cholesterol) might reduce amyloid deposits, Dr Gottesman responded,Although our study was not designed to specifically answer this question, and as an observational study cannot clearly show that modification of these risk factors reduces amyloid deposition in later life, this is one implication of the results. The particular importance of these risk factors is that they are all in theory modifiable, and as of now there are no other known ways to prevent or treat Alzheimer's disease."

References

  1. Gottesman RF, Schneider AL, Zhou Y, et al. Association between midlife vascular risk factors and estimated brain amyloid deposition. JAMA. 2017;317:1443-1450.
  2. Freitag MH, Peila R, Masaki K, et al. Midlife pulse pressure and incidence of dementia:the Honolulu-Asia Aging Study. Stroke. 2006;37:33-37.
  3. Launer LJ, Masaki K, Petrovitch H, Foley D, Havlik RJ. The association between midlife blood pressure levels and late-life cognitive function: the Honolulu-Asia Aging Study. JAMA. 1995;274:1846-1851.
  4. Alonso A, Mosley TH Jr, Gottesman RF, et al. Risk of dementia hospitalisation associated with cardiovascular risk factors in midlife and older age: the Atherosclerosis Risk in Communities (ARIC) study. J Neurol Neurosurg Psychiatry. 2009;80:1194-1201.
  5. Kivipelto M, Helkala EL, Laakso MP, et al. Midlife vascular risk factors and Alzheimer's disease in later life: longitudinal, population based study. BMJ. 2001;322:1447-1451.
  6. Ott A, Stolk RP, van Harskamp F, et al. Diabetes mellitus and the risk of dementia: the Rotterdam Study. Neurology. 1999;5:1937-1942.
  7. Hern.n MA, Alonso A, Logroscino G. Cigarette smoking and dementia: potential selection bias in the elderly. Epidemiology. 2008;19:448-450.
  8. Solomon A, Kivipelto M,Wolozin B, Zhou J, et al. Midlife serum cholesterol and increased risk of Alzheimer's and vascular dementia three decades later. Dement Geriatr Cogn Disord. 2009;28:75-80.
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