Background: Subjective cognitive complaint (SCC) is common in older adults. It may represent the earliest clinical manifestation of cognitive decline and Alzheimer’s disease (AD). Objectives: 1) to evaluate the association between SCC and its severity (SoC) at baseline and the presence of AD pathology; and 2) to identify specific complaints through questions of the Cognitive Complaint Inventory (CCI) best predict AD pathology; and 3) to evaluate whether using SCC related scores or specific questions may improve the prediction of cognitive decline. Method: We conducted a study in 164 non-demented subjects participating on a longitudinal study in a memory clinic setting, aged 53 to 88 years, with CDR scores of 0 (N=84) and 0.5 (N=80). SCC was assessed using the Cognitive Complaint Inventory (CCI), a validated 10 items questionnaire. Accordingly, SCC was defined as being present when the subject answers “yes” to 3 or more questions; and/or to question 5 (forget an event), and/or to the questions A (reporting a memory change), 4 (difficulties with spatial orientation), 5, 7 (limitation of activities), 8 (personality change). All participants underwent comprehensive neuropsychological evaluations and CSF biomarkers analysis. “Amyloid positivity" and “AD pathology” were defined according to CSF Aβ42 levels and CSF pTau181/Aβ42 ratio, respectively. Logistic regression analyses were used to address the associations of interest. Results: Participants with SCC had significantly lower CSF Aβ42 and higher CSF Tau and pTau181 levels compared to those without SCC. In CDR=0.5 subgroup, SCC and question A were negatively associated with AD pathology while SoC was predictive of AD pathology. question 6 was negatively associated with AD pathology in the CDR=0 subgroup.
A model including age, sex, years of education, CDRSoB, and the questions A, 2, 4 and 5 showed better prediction of decline at first follow-up compared to the reference model (AUC: 0.866, p=0.032). At last follow-up, a positive answer on question 6, increasing age and lower baseline CDR were associated with future cognitive decline.
Conclusion: Severity of complaint rather than SCC was predictive of cerebral AD pathology in the CDR=0.5 subgroup but not in the CDR=0 subgroup. Having reported subjective difficulties in finding words at baseline together with increasing age and low CDR at baseline were predictive of decline at second follow-up.