Cognitive impairment in remitted late-life depression is not associated with Alzheimer's disease-related CSF biomarkers

Abstract

BackgroundCognitive impairment is a common feature of late-life depression (LLD). Early studies using Alzheimer's disease (AD) biomarkers inferred a biological link between AD pathology and LLD, but recent findings have challenged this association. The aim of this investigation was to determine a panel of AD-related cerebrospinal fluid (CSF) biomarkers in a cross-section of elders with mild cognitive impairment (MCI) with and without LLD. MethodsSubjects comprised 102 older adults: 27 with ‘pure' amnestic MCI (aMCI), 53 with major depression and cognitive impairment – encompassing 22 late-onset (LOD) and 31 early-onset depression (EOD), and 22 euthymic elders without cognitive impairment (controls). Participants underwent lumbar puncture for determination of CSF concentrations of Aβ1-42, T-tau, and P-tau. Cut-off scores for suspected AD were: Aβ1-42 < 416p g/mL, P-tau > 36.1 pg/mL and Aβ/P-tau ratio < 9.53 (O. V. Forlenza et al. 2015). Statistical analyses consisted of analyses of variance (ANOVA), analyses of covariance (ANCOVA), Bonferroni post-hoc tests, and Pearson's chi-squared tests. ResultsANCOVA (age and schooling as covariates) displayed statistically significant results with respect to CSF biomarkers’ profiles regardless of the socio-demographic divergencies previously identified by one-way ANOVA. Mean Aβ1-42 values (pg/mL) were: aMCI, 360.3 (p < 0.001); LOD, 486.6 (p < 0.001); EOD, 494.2 (p < 0.001); controls, 528.3 (p < 0.001); p< 0.05. Mean Aβ1-42/P-tau ratio: aMCI, 7.9 (p < 0.001); LOD 14.2 (p < 0.001); EOD, 15.3 (p < 0.001); controls, 17.1 (p < 0.001); p < 0.05. Post-hoc tests indicated that patients with aMCI showed significant differences in biomarker profile compatible with AD signature. LimitationThe main limitation is the relatively small sample. ConclusionOur findings suggest that, distinctively from aMCI, cognitive impairment in LLD is not associated with AD's CSF pathological signature.