Visual memory tests enhance the identification of amnestic MCI cases at greater risk of Alzheimer’s disease

Objectives: To investigate whether amnestic mild cognitive impairment (aMCI) identified with visual memory tests conveys an increased risk of Alzheimer’s disease (risk-AD) and if the risk-AD differs from that associated with aMCI based on verbal memory tests. Participants: 4,771 participants aged 70.76 (SD = 6.74, 45.4% females) from five community-based studies, each a member of the international COSMIC consortium and from a different country, were classified as having normal cognition (NC) or one of visual, verbal, or combined (visual and verbal) aMCI using international criteria and followed for an average of 2.48 years. Hazard ratios (HR) and individual patient data (IPD) meta-analysis analyzed the risk-AD with age, sex, education, single/multiple domain aMCI, and Mini-Mental State Examination (MMSE) scores as covariates. Results: All aMCI groups (n = 760) had a greater risk-AD than NC (n = 4,011; HR range = 3.66 – 9.25). The risk-AD was not different between visual (n = 208, 17 converters) and verbal aMCI (n = 449, 29 converters, HR = 1.70, 95%CI: 0.88, 3.27, p = 0.111). Combined aMCI (n = 103, 12 converters, HR = 2.34, 95%CI: 1.13, 4.84, p = 0.023) had a higher risk-AD than verbal aMCI. Age and MMSE scores were related to the risk-AD. The IPD meta-analyses replicated these results, though with slightly lower HR estimates (HR range = 3.68, 7.43) for aMCI vs. NC. Conclusions: Although verbal aMCI was most common, a significant proportion of participants had visual-only or combined visual and verbal aMCI. Compared with verbal aMCI, the risk-AD was the same for visual aMCI and higher for combined aMCI. Our results highlight the importance of including both verbal and visual memory tests in neuropsychological assessments to more reliably identify aMCI.Funding for COSMIC comes from a National Health and Medical Research Council of Australia Program Grant (ID 1093083), the National Institute on Aging of the National Institutes of Health (under Award No. RF1AG057531), and philanthropic contributions to the Dementia Momentum Fund (UNSW Project ID PS38235). Andrea R. Zammit was supported by the National Institute on Aging of the National Institutes of Health (under Award No. K01AG054700). HELIAD study was supported by the following grants: IIRG-09133014 from the Alzheimer’s Association; 189 10276/8/9/2011 from the ESPA-EU program Excellence Grant (ARISTEIA), which is co-funded by the European Social Fund and Greek National resources, and ΔΥ2β/ικ.51657/14.4.2009 from the Ministry for Health and Social Solidarity (Greece). KLOSCAD was funded by a grant from the Korean Health Technology R&D Project, Ministry of Health and Welfare, Republic of Korea (Grant No. HI09C1379 [A092077]). EAS was supported in part by National Institutes of Health grants (NIA 2 P01 AG03949), the Leonard and Sylvia Marx Foundation, and the Czap Foundation