Cerebrospinal fluid neurofilament light chain mediates age-associated lower learning and memory in healthy adults.

Multiple cognitive domains, including learning, memory, and psychomotor speed, show significant reductions with age. Likewise, several cerebrospinal fluid (CSF) neurodegenerative biomarkers, including total tau (t-tau, a marker of neuronal body injury) and neurofilament light chain (NfL, a marker of axonal injury) show age-related increases in normal aging. In the current study, we aimed to investigate whether the age-effect within different cognitive domains was mediated by age-associated CSF markers for neurodegenerative changes. We fitted 10 mediation models using structural equation modeling to investigate this in a cohort of 137 healthy adults, aged 40-80 years, from the Norwegian Dementia Disease Initiation (DDI) study. Here, t-tau and NfL were defined as mediators between age and different cognitive tests. The models showed that NfL mediated the age-effect for CERAD learning and memory recall (learning: ß = -0.395, p < 0.05; recall: ß = -0.261, p < 0.01). No such effect was found in the other models. Our findings suggest that the age-related lower performance in verbal learning and memory may be linked to NfL-associated neurodegenerative changes in cognitively healthy adults.

Regression-based cognitive change norms applied in biochemically defined predementia Alzheimer's disease.

OBJECTIVE: We aim to develop 2-year cognitive change norms for adults ages 41-84 for six cognitive tests, and to evaluate these norms in groups with AD biomarkers. BACKGROUND: Practice effects are common in repeated neuropsychological testing. Not accounting for practice effects may obscure cognitive decline in early Alzheimer's disease (AD). METHOD: We developed standardized regression-based change norms from normative samples consisting of healthy controls from the Dementia Disease Initiation study (n = 125), the Trønderbrain study (n = 57), and the Gothenburg mild cognitive impairment (MCI) study (n = 65). Norms were applied in a sample with cognitive symptoms (subjective cognitive decline or MCI) and AD cerebrospinal fluid (CSF) biomarkers (n = 246), classified according to the A/T/N system. RESULTS: The change norms adjusted for pertinent demographics and practice effects. The group with cognitive complaints displayed a trend toward cognitive decline compared to the normative group, with the A +T/N + subgroup showing the most marked decline. This was observed in tests of episodic memory and cognitive flexibility/divided attention. CONCLUSIONS: We present 2-year cognitive change norms for adults between 41 and 84 years, adjusted for practice and demographics. A web-based change norm calculator is provided. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The Cognitive Profile of Mild Cognitive Impairment Due to Dementia With Lewy Bodies-An Updated Review.

Objective: Dementia with Lewy Bodies (DLB) is the second most common type of neurodegenerative dementia. Yet, the domain-specific cognitive impairment of the mild cognitive impairment (MCI) phase of this disease (DLB-MCI) is still not been established. This article gives an updated review on the neuropsychological profile of DLB-MCI, building on the findings from a previous review. Methods: We performed systematic review and searched five different electronic databases (Scopus, Cochrane, EMBASE, MEDLINE, and PsycINFO) in May 2020 based on a PICO scheme. Our search was then restricted to articles published in 2019 and 2020. Ending up with a total of 90 articles to be reviewed by abstract and/or full text. Results: In total four papers were included, whereof only one met our full inclusion criteria. Despite a substantial heterogeneity, our findings indicate that DLB-MCI patients have a pattern of executive, visuospatial, and attentional deficits. Conclusion: The findings indicate that the neuropsychological profile of DLB-MCI is characterized by executive, visuospatial, and attentional deficits. Furthermore, the shortage of studies clearly underlines the paucity of published research into DLB-MCI and emphasizes the need for well-controlled studies.