The role of vascular risk factors in brain pathology

Numerous studies have linked APOE ɛ4 and vascular factors to dementia, including AD. In the Kungsholmen Project, we found that APOE ɛ4 is a major risk factor for MCI1, AD, and dementia, but not all ɛ4-carriers develop dementia. Indeed, we identified some factors that may modify the risk of dementia due to ɛ4: high education, active participation in leisure activities, and maintaining vascular health2. A further study supported this last finding, as we found that education counteracted the risk due to APOE3.

Several reports have linked midlife obesity to dementia in late life. We found that both overweight and obesity at midlife independently increase the risk of dementia, AD, and vascular dementia. Genetic and early-life environmental factors may contribute to the midlife high adiposity-dementia association4.

Finally, in the SNAC-K MRI sample (n=523, age ≥ 60 years, 59.3% women), we investigated the association between vascular factors and pathological changes in the brain. We found that as the number of vascular risk factors increased, the volume of the hippocampus and entorhinal cortex decreased significantly5. These associations were evident only among men, suggesting that in men, the medial temporal lobe is more vulnerable to cardiovascular risk factors than in women. In the AGES-Reykjavik Study (n=4205, mean age 76 years, 58% women), cerebral microbleeds had a prevalence of 11.3% and were not associated with age-related macular degeneration, a finding that does not support the hypothesis that amyloid deposits in the retina and the brain are correlated6.

  1. Xu WL, Caracciolo B, Wang HX, Santoni G, Winblad B, Fratiglioni L. Accelerated progression from mild cognitive impairment to dementia among APOE ɛ4ɛ4 carriers. J Alzheimers Dis 2013; 33(2):507-15.
  2. Ferrari C, Xu WL, Wang HX, Winblad B, Fratiglioni L. How can elderly APOE ɛ4 carriers remain free from dementia? Neurobiol Aging 2013; 34(1):13-21.
  3. Wang HX, Gustafson DR, Kivipelto M, Pedersen NL, Skoog I, Windblad B, et al. Education halves the risk of dementia due to apolipoprotein ε4 allele: a collaborative study from the Swedish Brain Power initiative. Neurobiol Aging 2012; 1007.e1–1007.e7.
  4. Xu W, Atti AR, Gatz M, Pedersen NL, Johansson B, Fratiglioni L. Midlife overweight and obesity increase late-life dementia risk: a population-based twin study. Neurology 2011; 76(18):1568-1574.
  5. Qiu C, Zhang Y, Bronge L, Herlitz A, Aspelin P, Bäckman L, et al. Medial temporal lobe is vulnerable to vascular risk factors in men: a population-based study. Eur J Neuro 2012; 19(6):876-883.
  6. Qiu C, Cotch MF, Sigurdsson S, et al. Cerebral microbleeds and age-related macular degeneration: the AGES-Reykjavik Study. Neurobiol Aging 2012; 33:2935-2937.