• Paula Iso-Markku, Jaakko Kaprio, Noora Lindgren, Juha O Rinne, and Eero Vuoksimaa.
• Institute for Molecular Medicine Finland, FIMM, Helsinki Institute of Life Sciences, HiLIFE, University of Helsinki, Helsinki, Finland paula.iso-markku@helsinki.fi.
• J. Neurol. Neurosurg. Psychiatr. 2021 Mar 1; 92 (3): 323-330.

BackgroundMiddle-age risk scores predict cognitive impairment, but it is not known if these associations are evident when controlling for shared genetic and environmental factors. Using two risk scores, self-report educational-occupational score and Cardiovascular Risk Factors, Aging and Dementia (CAIDE), we investigated if twins with higher middle-age dementia risk have poorer old-age cognition compared with their co-twins with lower risk.MethodsWe used a population-based older Finnish Twin Cohort study with middle-age questionnaire data (n=15 169, mean age=52.0 years, SD=11.8) and old-age cognition measured via telephone interview (mean age=74.1, SD=4.1, n=4302). Between-family and within-family linear regression analyses were performed.ResultsIn between-family analyses (N=2359), higher educational-occupational score was related to better cognition (B=0.76, 95% CI 0.69 to 0.83) and higher CAIDE score was associated with poorer cognition (B=-0.73, 95% CI -0.82 to -0.65). Within twin-pair differences in educational-occupational score were significantly related to within twin-pair differences in cognition in dizygotic (DZ) pairs (B=0.78, 95% CI 0.25 to 1.31; N=338) but not in monozygotic (MZ) pairs (B=0.12, 95% CI -0.44 to 0.68; N=221). Within twin-pair differences in CAIDE score were not related to within twin-pair differences in cognition: DZ B=-0.38 (95% CI -0.90 to 0.14, N=343) and MZ B=-0.05 (95% CI -0.59 to 0.49; N=226).ConclusionMiddle-age dementia risk scores predicted old-age cognition, but within twin-pair analyses gave little support for associations independent of shared environmental and genetic factors. Understanding genetic underpinnings of risk score-cognition associations is important for early detection of dementia and designing intervention trials.© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

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