Objective To investigate the effect of familial risk for dementia on verbal learning by comparing cognitively healthy twins who had demented co-twins with cognitively healthy twins who had cognitively healthy co-twins.
Methods 4367 twins aged ≥65 years including 1375 twin pairs (533 monozygotic (MZ), 823 dizygotic (DZ) and 19 unknown zygosity pairs) from a population-based Finnish Twin Cohort participated in a cross-sectional telephone assessment for dementia and in a single free recall trial of a 10-item word list.
Results Cognitively healthy twins with demented co-twins (n=101 pairs) recalled less words than cognitively healthy twins with cognitively healthy co-twins (n=770 pairs) after adjusting for age, sex and education, B=− 0.44, 95% CI (−0.73 to −0.14), p=0.003. The effect size was similar in MZ (n=31) twins (3.88 vs 4.29 words, B=−0.41, 95% CI (−0.96 to 0.13)) and DZ (n=66) twins (3.70 vs 4.17 words, B=−0.47, 95% CI (−0.84 to −0.10)). The heritability estimate of immediate recall (IR) was 0.37, 95% CI (0.21 to 0.43).
Conclusions The results demonstrate that familial risk for dementia is reflected in the IR performance of cognitively healthy older persons. The finding of poorer IR performance in non-affected siblings compared with the general population, together with substantial heritability of IR, supports IR as a useful endophenotype for molecular genetic studies of dementia.
- memory and learning tests
- verbal learning
- twin study
- free recall
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Contributors NL: drafting the manuscript, study concept and design, analysis and interpretation of data, acquisition of data and statistical analysis. JK: recruitment of the study cohort, supervision of data collection and interpretation of data. JOR: study concept and design, interpretation of data, revising the manuscript, study supervision and obtaining funding. EV: drafting/revising the manuscript, study concept and design, analysis and interpretation of data, statistical analysis and study supervision. All authors have provided critical comments on the manuscript and approved the final version.
Funding This work was supported by Sigrid Juselius Foundation and Finnish Governmental Research Funding. NL was supported by the Finnish Cultural Foundation, Yrjö Jahnsson Foundation, Turku University Foundation and Finnish Brain Foundation. JK was supported by the Academy of Finland (grants 265240 & 263278). EV was supported by Juho Vainio Foundation and the Academy of Finland (grant 314639).
Competing interests JOR serves as a neurology consultant for Clinical Research Services Turku (CSRT Oy).
Patient consent Not required.
Ethics approval The telephone interview protocol was approved by the Ethics Committee of the Hospital District of Southwest Finland and informed consent was obtained from participants. Questionnaire studies in 1975 and 1981 were approved by the National Board of Health and answering the questionnaire was considered as consent.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement Due to the consent given by study participants and the high degree of identifiability, data cannot be made publicly available. Data are available through the Institute for Molecular Medicine Finland (FIMM) Data Access Committee (DAC) for authorised researchers who have IRB/ethics approval and an institutionally approved study plan. For more details, please contact the FIMM DAC (email@example.com).
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