Sara Kaffashian

Objective: We investigated the relation of circulating plasma β-amyloid (Aβ) with MRI markers of small vessel disease (SVD) in dementia-free community persons. Methods: Participants were 1,690 individuals aged 65 to 80 years from the Three-City Dijon Study. Plasma Aβ measurement and MRI examination were performed at baseline and after a 4-year follow-up. MRI markers of SVD included white matter hyperintensities (WMH), lacunes, and enlarged perivascular spaces. We examined the relation of plasma Aβ levels with MRI markers of SVD at baseline and with progression of WMH over follow-up (n = 1,057). We also assessed whether these relations were modified by vascular risk factors, notably blood pressure. Results: Low plasma Aβ_1–40 levels were associated with increased progression of WMH, and low Aβ_1–42 with higher odds of extensive WMH progression over the follow-up (odds ratio = 1.66, 95% confidence interval = 1.16–2.38). Consistently low Aβ_1–40 and Aβ_1–42 levels on both measurements were associated with accelerated progression of WMH. These associations were modified by blood pressure levels but not the APOE ε4 genotype. Conclusions: Progression of WMH volume in dementia-free older persons is associated with levels of circulating plasma Aβ. These results reinforce the notion of an interrelation of vascular and neurodegenerative mechanisms in cerebral aging.

Objective: Our aim was to compare 2 Framingham vascular risk scores with a dementia risk score in relation to 10-year cognitive decline in late middle age. Methods: Participants were men and women with mean age of 55.6 years at baseline, from the Whitehall II study, a longitudinal British cohort study. We compared the Framingham general cardiovascular disease risk score and the Framingham stroke risk score with the Cardiovascular Risk Factors, Aging and Dementia (CAIDE) risk score that uses risk factors in midlife to estimate risk of late-life dementia. Cognitive tests included reasoning, memory, verbal fluency, vocabulary, and global cognition, assessed 3 times over 10 years. Results: Higher cardiovascular disease risk and higher stroke risk were associated with greater cognitive decline in all tests except memory; higher dementia risk was associated with greater decline in reasoning, vocabulary, and global cognitive scores. Compared with the dementia risk score, cardiovascular and stroke risk scores showed slightly stronger associations with 10-year cognitive decline; these differences were statistically significant for semantic fluency and global cognitive scores. For example, cardiovascular disease risk was associated with −0.06 SD (95% confidence interval [CI] = −0.08, −0.05) decline in the global cognitive scores over 10 years whereas dementia risk was associated with −0.03 SD (95% CI = −0.04, −0.01) decline (difference in β coefficients = 0.03; 95% CI = 0.01, 0.05). Conclusions: The CAIDE dementia and Framingham risk scores predict cognitive decline in late middle age but the Framingham risk scores may have an advantage over the dementia risk score for use in primary prevention for assessing risk of cognitive decline and targeting of modifiable risk factors.

Background: Stroke is associated with an increased risk of dementia. However, it is unclear whether risk of stroke in those free of stroke, particularly in nonelderly populations, leads to differential rates of cognitive decline. Our aim was to assess whether risk of stroke in mid life is associated with cognitive decline over 10 years of follow‐up.Methods: We studied 4153 men and 1657 women (mean age, 55.6 years at baseline) from the Whitehall II study, a longitudinal British cohort study. We used the Framingham Stroke Risk Profile (FSRP), which incorporates age, sex, systolic blood pressure, diabetes mellitus, smoking, prior cardiovascular disease, atrial fibrillation, left ventricular hypertrophy, and use of antihypertensive medication. Cognitive tests included reasoning, memory, verbal fluency, and vocabulary assessed three times over 10 years. Longitudinal associations between FSRP and its components were tested using mixed‐effects models, and rates of cognitive change over 10 years were estimated.Results: Higher stroke risk was associated with faster decline in verbal fluency, vocabulary, and global cognition. For example, for global cognition there was a greater decline in the highest FSRP quartile (−0.25 of a standard deviation; 95% confidence interval: −0.28 to −0.21) compared with the lowest risk quartile (P = .03). No association was observed for memory and reasoning. Of the individual components of FSRP, only diabetes mellitus was associated independently with faster cognitive decline (β = −0.06; 95% confidence interval, −0.01 to 0.003; P = .03).Conclusion: Elevated stroke risk at midlife is associated with accelerated cognitive decline over 10 years. Aggregation of risk factors may be especially important in this association.

Background: the burden associated with osteoporotic fractures has commonly been reported in terms of utilisation of acute care. However, individuals with fractures suffer lasting deficits in quality of life and the burden of care extends well beyond the initial acute care period. The burden of fractures related to post-acute heath care utilisation, and informal care giving, has not been sufficiently addressed. We examine the use of formal and informal post-acute care in men and women 50 years and older who sustained fractures. Methods: the study sample consisted of 1,116 men and women from the Canadian Multicentre Osteoporosis Study (CaMos) who sustained a fracture. We assessed utilisation of post-acute care including rehabilitative and home care services, as well as informal care in persons with a hip, vertebral, or non-hip-non-vertebral fractures. Results: use of rehabilitative and home care services was reported by 37.1% and 18.2% of men and women, respectively. Persons with hip fracture were more likely to report use of these services compared with persons with non-hip-non-vertebral fractures; those with vertebral fracture were less likely to report using these services. Use of informal care was reported by 47.2% of participants. Individuals with multiple fractures made more extensive use of post-acute resources compared with those with single fractures. Conclusions: use of post-acute care in individuals with fracture is extensive and the contribution of use of these resources to the overall burden of fractures cannot be ignored. Our findings have implications for future economic analyses and policy-making related to care of osteoporotic fractures.

Vascular risk factors are associated with cognitive impairment and dementia, although most of the research in this domain focuses on cerebrovascular factors. We examined the relationship between the recently developed Framingham general cardiovascular risk profile and cognitive function and 10-year decline in late midlife. Study sample comprised of 3486 men and 1341 women, mean age 55 years [standard deviation (SD)=6], from the Whitehall II study, a longitudinal British cohort study. The Framingham General Cardiovascular Risk profile, assessed between 1997 and 1999, included age, sex, HDL cholesterol, total cholesterol, systolic blood pressure, smoking status, and diabetes status. Measures of cognitive function consisted of tests of reasoning (Alice Heim 4-I), memory, phonemic and semantic fluency, and vocabulary (Mill-Hill), assessed three times (1997–1999, 2002–2004, 2007–2009) over 10 years. In cross-sectional age-adjusted models, 10% point increments in cardiovascular risk were associated with poor performance in all cognitive domains in both men and women (all P-values <0.001). In models adjusted for age, ethnicity, marital status, and education, 10% higher cardiovascular risk was associated with greater overall 10-year cognitive decline in men, reasoning in particular (−0.47; 95% CI: −0.81, −0.11). In middle-aged individuals free of cardiovascular disease, an adverse cardiovascular risk profile is associated with poor cognitive function, and decline in at least one cognitive domain in men.