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. 2022 Aug 22;14(1):114.
doi: 10.1186/s13195-022-01060-1.

Tau levels are higher in objective subtle cognitive decline but not subjective memory complaint

Kelsey R Thomas  1   2 , Alexandra J Weigand  3 , Lauren C Edwards  3 , Emily C Edmonds  4 , Katherine J Bangen  5   6 , Gema Ortiz  5 , Kayla S Walker  5   7 , Mark W Bondi  6   8 ; Alzheimer’s Disease Neuroimaging Initiative
Affiliations

Tau levels are higher in objective subtle cognitive decline but not subjective memory complaint

Kelsey R Thomas et al. Alzheimers Res Ther. .

Abstract

Background: The 2018 NIA-AA Alzheimer's Disease (AD) Research Framework states that subtle cognitive decline in cognitively unimpaired individuals can be measured by subjective reports or evidence of objective decline on neuropsychological measures. Both subjective memory complaint (SMC) and objective subtle cognitive decline (Obj-SCD) have been shown to be associated with future cognitive decline and AD biomarkers. We examined whether there are differences in tau PET levels between (a) SMC- vs. SMC+ participants, (b) Obj-SCD- vs. Obj-SCD+ participants, and (c) participants with overlapping vs. discrepant SMC and Obj-SCD classifications.

Methods: Cognitively unimpaired participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI; n = 236) were classified at baseline as positive or negative for SMC (SMC- n = 77; SMC+ n = 159) based on the first 12 items of the Cognitive Change Index and/or classified as positive or negative for Obj-SCD (Obj-SCD- n = 173; Obj-SCD+ n = 63) based on previously defined neuropsychological criteria. Analyses of covariance, adjusting for age, sex, APOE ε4 carrier status, and pulse pressure, examined the group differences in tau PET (AV-1451) using a composite standardized uptake variable ratio (SUVR) for regions consistent with Braak stage III/IV. The chi-squared tests examined the tau positivity rates across the groups.

Results: Obj-SCD+ participants had higher tau continuous SUVR levels (p = .035, ηp2 = .019) and higher rates of tau positivity (15.8% Obj-SCD- vs. 30.2% Obj-SCD+) than Obj-SCD- participants. Neither tau levels (p = .381, ηp2 = .003) nor rates of tau positivity (18.2% SMC- and 20.1% SMC+) differed between the SMC groups. There was very little agreement between SMC and Obj-SCD classifications (42%; κ = 0.008, p = .862). Participants who were Obj-SCD+ without SMC had the highest tau PET levels and differed from participants who were SMC+ without Obj-SCD (p = .022). Tau levels in participants with both SMC and Obj-SCD did not differ from those with only Obj-SCD (p = .216). Tau positivity rates across the SMC-/Obj-SCD-, SMC+/Obj-SCD-, SMC-/Obj-SCD+, and SMC+/Obj-SCD+ groups were 10.5%, 18.1%, 40.0%, and 25.6%, respectively.

Conclusion: Participants with Obj-SCD had a greater tau PET burden than those without Obj-SCD, but SMC was not associated with higher tau levels. The combination of SMC and Obj-SCD did not have higher tau levels than Obj-SCD alone. Findings add to the evidence that the Obj-SCD classification is associated with AD biomarkers and faster cognitive decline in ADNI participants, but further work is needed to validate this approach in more representative/diverse cohorts.

Keywords: Biomarkers; Neuropsychology; Preclinical Alzheimer’s disease; Subjective memory complaints; Subjective memory concern; Subtle cognitive decline; Tau PET.

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Conflict of interest statement

Dr. Bondi receives royalties from Oxford University Press. The other authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Braak III/IV SUVR by SMC status and Obj-SCD status. Dot-box plots show residual Braak III/IV values by subjective memory complaint (SMC) status (a) and objective subtle cognitive decline (Obj-SCD) status (b). Covariates included age, sex, APOE ε4 carrier status, and pulse pressure. *p < .05
Fig. 2
Fig. 2
Braak III/IV SUVR by overlapping/discrepant SMC and Obj-SCD classifications. Dot-box plot shows residual Braak III/IV values by subjective memory complaint (SMC) and objective subtle cognitive decline (Obj-SCD) status. Covariates included age, sex, APOE ε4 carrier status, and pulse pressure. *p < .05
See this image and copyright information in PMC

References

    1. Sperling RA, Rentz DM, Johnson KA, Karlawish J, Donohue M, Salmon DP, et al. The A4 Study: stopping AD before symptoms begin? Sci Transl Med. 2014;6(228):228fs13. doi: 10.1126/scitranslmed.3007941. - DOI - PMC - PubMed
    1. Jack CR, Jr, Bennett DA, Blennow K, Carrillo MC, Dunn B, Haeberlein SB, et al. NIA-AA Research Framework: toward a biological definition of Alzheimer’s disease. Alzheimers Dement. 2018;14(4):535–562. doi: 10.1016/j.jalz.2018.02.018. - DOI - PMC - PubMed
    1. Thomas KR, Bangen KJ, Weigand AJ, Edmonds EC, Wong CG, Cooper S, et al. Objective subtle cognitive difficulties predict future amyloid accumulation and neurodegeneration. Neurology. 2020;94(4):e397–e406. doi: 10.1212/WNL.0000000000008838. - DOI - PMC - PubMed
    1. Thomas KR, Edmonds EC, Eppig J, Salmon DP, Bondi MW, Initiative ADN. Using neuropsychological process scores to identify subtle cognitive decline and predict progression to mild cognitive impairment. J Alzheimers Dis. 2018;64(1):195–204. doi: 10.3233/JAD-180229. - DOI - PMC - PubMed
    1. Amariglio RE, Becker JA, Carmasin J, Wadsworth LP, Lorius N, Sullivan C, et al. Subjective cognitive complaints and amyloid burden in cognitively normal older individuals. Neuropsychologia. 2012;50(12):2880–2886. doi: 10.1016/j.neuropsychologia.2012.08.011. - DOI - PMC - PubMed

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