Relevance of Minor Neuropsychological Deficits in Patients With Subjective Cognitive Decline

Abstract

Background and Objectives:To determine the relevance of minor neuropsychological deficits (MNPD) in patients with subjective cognitive decline (SCD) with regard to CSF levels of Alzheimer’s disease (AD) biomarkers, cognitive decline and clinical progression to mild cognitive impairment (MCI).Methods:This study included clinical SCD patients and SCD free, healthy control (HC) participants with available baseline CSF and/or longitudinal cognitive data from the observationalDZNE Longitudinal Cognitive Impairment and Dementia(DELCODE) study. We defined MNPD as a performance of at least 0.5SD below the mean on a demographically adjusted total score derived from theConsortium to Establish a Registry for Alzheimer’s DiseaseNeuropsychological Assessment Battery. We compared SCD patients with MNPD and those without MNPD with regard to CSF amyloid-β (Aβ)42/Aβ40, phosphorylated tau (p-tau181),total tau and Aβ42/p-tau181levels, longitudinal cognitive composite trajectories and risk of clinical progression to incident MCI (follow-upM±SD: 40.6±23.7 months). Additionally, we explored group differences between SCD and HC in those without MNPD.Results:In our sample (N = 672, mean age: 70.7±5.9 years, 50% female), SCD patients with MNPD (n = 55, 12.5% of SCD group) showed significantly more abnormal CSF biomarker levels, increased cognitive decline and a higher risk of progression to incident MCI (HR: 4.07, 95%CI: 2.46-6.74) compared to SCD patients without MNPD (n = 384). MNPD had a positive predictive value of 57.0% (95%CI: 38.5-75.4) and a negative predictive value of 86.0% (95%CI: 81.9-90.1) for the progression of SCD to MCI within three years. SCD patients without MNPD showed increased cognitive decline and a higher risk of incident MCI compared to HC participants without MNPD (n = 215; HR: 4.09, 95%CI: 2.07-8.09), while AD biomarker levels did not differ significantly between these groups.Discussion:Our results suggest that MNPD are a risk factor for AD related clinical progression in cognitively normal patients seeking medical counseling due to SCD. As such, the assessment of MNPD could be useful for individual clinical prediction and for AD risk stratification in clinical trials. However, SCD remains a risk factor for future cognitive decline even in the absence of MNPD.

Brain Health and Cognition in Older Adults: Roadmap and Milestones towards the Implementation of Preventive Strategies

“…In turn, SCD without minor deficits had a four-fold risk of progression to MCI compared to healthy controls without SCD. Interestingly, CSF AD biomarkers were significantly different in SCD with minor deficits compared to SCD without them (but the latter did not differ from healthy controls without SCD) [25]. It may be worth noticing that unimpaired controls were allowed to experience age-appropriate subjective subtle cognitive decline provided that they were not worried about it.…”

A remote digital memory composite to detect cognitive impairment in memory clinic samples in unsupervised settings using mobile devices

“…A PACC5 composite score was calculated when at least three of its five components were available while making sure that at least the MMSE, one memory measure, and either category fluency or DSCT were included. In the DELCODE cohort, the clinical labels (HC, SCD, MCI) were established at the baseline assessment of each participant, and follow-up diagnoses were established in April 2021 41 . At the Memory Clinic of the University of Magdeburg, which is a DELCODE recruitment site, additional participants were prospectively recruited according to the DELCODE neuropsychological protocol.…”

Blood biomarkers confirm subjective cognitive decline (SCD) as a distinct molecular and clinical stage within the NIA-AA framework of Alzheimer’s disease

“…The observed changes were specifically contrasted to the alterations in both CU and MCI individuals, thus allowing to validate SCD as a distinct clinical and molecular stage in the predementia AD continuum. [30]. In MCI patients, incident dementia was diagnosed by the study physician according to established criteria.…”