Article Text

Original research
Middle-age dementia risk scores and old-age cognition: a quasi-experimental population-based twin study with over 20-year follow-up
  1. Paula Iso-Markku1,2,
  2. Jaakko Kaprio1,3,
  3. Noora Lindgren4,
  4. Juha O Rinne4,
  5. Eero Vuoksimaa1
  1. 1Institute for Molecular Medicine Finland, FIMM, Helsinki Institute of Life Sciences, HiLIFE, University of Helsinki, Helsinki, Finland
  2. 2HUS Diagnostic Center, Clinical Physiology and Nuclear Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
  3. 3Clinicum, Department of Public Health, University of Helsinki Faculty of Medicine, Helsinki, Finland
  4. 4Turku PET Centre, University of Turku, Turku, Finland
  1. Correspondence to Dr Paula Iso-Markku, FIMM, University of Helsinki Helsinki Institute of Life Sciences, Helsinki 00014, Finland; paula.iso-markku{at}


Background Middle-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.

Methods We 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.

Results In 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).

Conclusion Middle-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.

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  • Contributors PI-M: study concept and design, statistical analysis, interpretation of data and drafting the manuscript. NL: acquisition of data, interpretation of data and revising the manuscript. JK: recruitment of the study cohort, supervision of data collection, interpretation of data, revising the manuscript and obtaining funding. JOR: supervision of data collection, interpretation of data, revising the manuscript and obtaining funding. EV: study concept and design, interpretation of data, statistical analysis, drafting/revising the manuscript, study supervision and obtaining funding. All authors have provided critical comments on the manuscript and approved the final version.

  • Funding This study was supported by the Juho Vainio Foundation and the Academy of Finland research grants (314639, 320109 to EV; 265240, 263278, 308248, 312073 to JK; 310962 to JOR). JOR was supported also by the Sigrid Juselius Foundation and Finnish State Research Funding. NL was supported by the Finnish Cultural Foundation, Päivikki and Sakari Sohlberg Foundation, Yrjö Jahnsson Foundation, Turku University Foundation, Finnish State Research Funding and Finnish Brain Foundation.

  • Competing interests JOR serves as a neurology consultant for Clinical Research Services Turku (CSRT Oy). PI-M, EV, JK and NL have nothing to disclose.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available on reasonable request. Because of 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 (fimm‐

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