Risk factors in middle age, cognitive decline, and dementia

a. Changes in Blood Pressure from midlife to late life in relation to dementia risk and cognitive decline. Elevated blood pressure (BP) has been associated with increased risk of dementia in several studies, but the impact of hypertension seems to be age-dependent. In the Cardiovascular Risk Factors, Aging and Dementia (CAIDE) study in Finland, we previously linked midlife hypertension to higher dementia risk two decades later. We are now continuing these studies by focusing on the relation between patterns of change in BP during three decades after midlife and dementia, and by using data from the more recent second CAIDE follow-up in addition to data from the first follow-up. Preliminary results show that compared to people without substantial decline in BP from midlife until 30 years later, CAIDE participants with a decline of more than 15 mmHg in systolic BP or more than 15 mmHg in diastolic BP had a significantly increased risk of developing dementia. A possible explanation for the relation between decreasing BP and dementia may be the effect of dementia-related diseases on brain areas involved in BP regulation (i.e., the insula). A bidirectional relation could thus be hypothesized: midlife hypertension increases the risk of dementia-related pathological processes, and once such processes start they can in turn affect BP regulation. In addition, we found that elevated systolic or diastolic BP in midlife was related to poorer psychomotor speed in late-life and that declining diastolic BP between midlife and first follow-up (20 years) was related to worsening of executive functioning between first and second follow-up (work in progress).

b. Changes in blood pressure from midlife to late life and structural magnetic resonance imaging findings. In the CAIDE MRI population, midlife hypertension was related to more severe white matter lesions, as was long-term hypertension during 20 years after midlife. Decreasing BP after midlife was also associated with white matter lesions even after controlling for antihypertensive treatment. In contrast, lipid-lowering drugs had a protective effect against white matter lesions1. In addition, midlife hypertension was related to a thinner cortex 28 years later in several brain areas, including the insular, frontal, and temporal cortices. In elderly people with thinner insular cortices, there was a continuous decline in systolic BP and an increase in pulse pressure after midlife, whereas in elderly people with thicker insular cortices, the decline in systolic BP started at older ages, paralleled by a decline in pulse pressure2.

c. Overweight/obesity and hypercholesterolemia. In the CAIDE MRI population, midlife overweight or obesity was related to more severe white matter lesions two decades later. Long-term (20 years) overweight or obesity also increased the risk of more severe white matter lesions1. However, we did not find any associations between body mass index, cholesterol, or the APOE ɛ4 allele and cortical thickness in this group of elderly people2.

d. Inflammation. The association between rheumatoid arthritis or arthritis and dementia/AD has been investigated in several studies; the hypothesis has been that the chronic inflammatory component of rheumatoid arthritis may promote/facilitate neurodegeneration. In the CAIDE study, we investigated the association between self-reported joint disorders (rheumatoid arthritis and other joint disorders) in midlife and cognitive status 21 years later3 and found an increased risk of cognitive impairment or  dementia if any joint disorder was present at midlife.

  1. Vuorinen M, Solomon A, Rovio S, Nieminen L, Kåreholt I, Tuomilehto J, et al. Changes in vascular risk factors from midlife to late life and white matter lesions: a 20-year follow-up study. Dement Geriatr Cogn Disord 2011; 31(2):119-125.
  2. Vuorinen M, Kåreholt I, Julkunen V, Spulber G, Niskanen E, Paajanen T, et al. Changes in vascular factors 28 years from midlife and late-life cortical thickness. Neurobiol Aging 2013; 34(1):100-109.
  3. Wallin K, Solomon S, Kåreholt I, Tuomilehto J, Soininen H, Kivipelto M. Midlife rheumatoid arthritis increases the risk of cognitive impairment two decades later: a population-based study. Alzheimers Dis 2012; 31(3):669-676.