Subtle Differences in Cognition in 70-Year-Olds with Elevated Cerebrospinal Fluid Neurofilament Light and Neurogranin: A H70 Cross-Sectional Study.

BACKGROUND: Most research on cerebrospinal fluid (CSF) neurofilament light protein (NfL) as a marker for neurodegeneration and neurogranin (Ng) for synaptic dysfunction has largely focused on clinical cohorts rather than population-based samples. OBJECTIVE: We hypothesized that increased CSF levels of NfL and Ng are associated with subtle cognitive deficits in cognitively unimpaired (CU) older adults. METHODS: The sample was derived from the Gothenburg H70 Birth Cohort Studies and comprised 258 CU 70-year-olds, with a Clinical Dementia Rating score of zero. All participants underwent extensive cognitive testing. CSF levels of NfL and Ng, as well as amyloid ß1 - 42, total tau, and phosphorylated tau, were measured. RESULTS: Participants with high CSF NfL performed worse in one memory-based test (Immediate recall, p = 0.013) and a language test (FAS, p = 0.016). Individuals with high CSF Ng performed worse on the memory-based test Supra Span (p = 0.035). When stratified according to CSF tau and Aß42 concentrations, participants with high NfL and increased tau performed worse on a memory test than participants normal tau concentrations (Delayed recall, p = 0.003). In participants with high NfL, those with pathologic Aß42 concentrations performed worse on the Delayed recall memory (p = 0.044). In the high Ng group, participants with pathological Aß42 concentrations had lower MMSE scores (p = 0.027). However, in regression analysis we found no linear correlations between CSF NfL or CSF Ng in relation to cognitive tests when controlled for important co-variates. CONCLUSION: Markers of neurodegeneration and synaptic pathology might be associated with subtle signs of cognitive decline in a population-based sample of 70-year-olds.

Cognitive Performance and Cerebrospinal Fluid Markers in Preclinical Alzheimer's Disease: Results from the Gothenburg H70 Birth Cohort Studies.

BACKGROUND: We have previously shown that older adults with preclinical Alzheimer's disease (AD) pathology in cerebrospinal fluid (CSF) had slightly worse performance in Mini-Mental State Examination (MMSE) than participants without preclinical AD pathology. OBJECTIVE: We therefore aimed to compare performance on neurocognitive tests in a population-based sample of 70-year-olds with and without CSF AD pathology. METHODS: The sample was derived from the population-based Gothenburg H70 Birth Cohort Studies in Sweden. Participants (n = 316, 70 years old) underwent comprehensive cognitive examinations, and CSF Aß-42, Aß-40, T-tau, and P-tau concentrations were measured. Participants were classified according to the ATN system, and according to their Clinical Dementia Rating (CDR) score. Cognitive performance was examined in the CSF amyloid, tau, and neurodegeneration (ATN) categories. RESULTS: Among participants with CDR 0 (n = 259), those with amyloid (A+) and/or tau pathology (T+, N+) showed similar performance on most cognitive tests compared to participants with A-T-N-. Participants with A-T-N+ performed worse in memory (Supra span (p = 0.003), object Delayed (p = 0.042) and Immediate recall (p = 0.033)). Among participants with CDR 0.5 (n = 57), those with amyloid pathology (A+) scored worse in category fluency (p = 0.003). CONCLUSION: Cognitively normal participants with amyloid and/or tau pathology performed similarly to those without any biomarker evidence of preclinical AD in most cognitive domains, with the exception of slightly poorer memory performance in A-T-N+. Our study suggests that preclinical AD biomarkers are altered before cognitive decline.