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Int J Epidemiol. 2014 Apr;43(2):600-10. doi: 10.1093/ije/dyt242. Epub 2013 Dec 26.

Early identification and heritability of mild cognitive impairment.

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Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA, Center of Excellence for Stress and Mental Health, VA San Diego Healthcare System, La Jolla, CA, USA, Psychology Service, VA San Diego Healthcare System, La Jolla, CA, USA, Computational Science Research Center, San Diego State University/Claremont Graduate University, San Diego, CA, USA, Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL, USA, Department of Public Health, University of Helsinki, Helsinki, Finland, Department of Statistics, St Louis University, St Louis, MO, USA, Research Service, VA St Louis Healthcare System, St Louis, MO, USA and Department of Psychology, Boston University, Boston, MA, USA.



Identifying mild cognitive impairment (MCI) in midlife could improve early identification of Alzheimer's disease (AD). Also, AD is highly heritable, but the heritability of MCI has not been established. We estimated prevalence rates, association with premorbid general cognitive ability (GCA) and heritability for different definitions of neuropsychologically defined MCI in adults in their 50s.


We examined 1126 twins aged 51-59 years when recruited into the Vietnam Era Twin Study of Aging (VETSA). Six neurocognitive domains were assessed using tests designed to avoid ceiling effects. To differentiate MCI from low overall ability, criteria included adjustment for GCA measured at approximately age 20 years.


As in older adults, prevalence rates varied widely. Among the lower prevalence rates were some definitions of multiple-domain MCI and single-domain amnestic MCI, which may be less likely than other MCI categories to revert to normal on follow-up. Low prevalence rates in middle-aged adults are also more likely to be valid. MCI was also associated with lower premorbid GCA. Heritability estimates for any MCI and amnestic MCI averaged .40-.48.


By testing multiple cognitive domains and avoiding ceiling effects, MCI can be identified before age 60 years. Premorbid GCA is a risk/protective factor, but deficits after adjusting for early adult GCA suggest additional processes leading to declining trajectories. Heritabilities were comparable to AD, suggesting MCI as an appropriate phenotype for genetic association studies. Full validation will require follow-up assessments (currently under way). Community-based studies are important for this early identification because adults of this age are unlikely to present in clinics.


Alzheimer’s disease; Cognitive decline; middle age; preclinical diagnosis; risk factor

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