Minor neuropsychological deficits in SCD: Association with AD biomarkers and cognitive decline

Abstract Background The clinical relevance and longitudinal impact of minor neuropsychological deficits (MND) in cognitively normal memory clinic patients with subjective cognitive decline (SCD) is still unclear. To address this, we set out to investigate whether MND in SCD patients are related to Alzheimer´s disease (AD) pathology and future cognitive decline. In addition, we wanted to assess whether SCD patients have an increased risk of neuropathology and cognitive decline even in the absence of MND. Method We included 233 cognitively normal, healthy control participants (HC) without subjective cognitive concerns and 439 memory clinic SCD patients with available baseline CSF and/or longitudinal cognitive data from the observational DZNE Longitudinal Cognitive Impairment and Dementia (DELCODE) study. Participants, who scored at least 0.5SD below the mean on a composite measure calculated from the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) neuropsychological assessment battery, were classified as having MND. We compared the resulting participant groups regarding their baseline CSF Aβ42/40, p‐tau 181 , t‐tau and Aβ42/p‐tau 181 levels, longitudinal preclinical Alzheimer´s cognitive composite (PACC5) trajectories and risk of progression to incident mild cognitive impairment (MCI). Result Compared to SCD patients without MND (n = 384), SCD patients with MND (n = 55, 12.5% of SCD sample) showed significantly elevated CSF AD biomarker levels, accelerated PACC5 decline and a higher risk of progression to incident MCI. Baseline MND 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 to incident MCI within 3 years. SCD patients without MND showed increased PACC5 decline and a higher risk of incident MCI compared to HC participants without MND (n = 215), but did not differ from HC participants in their CSF biomarker levels. Conclusion MND are a risk factor for AD pathology and cognitive decline in memory clinic patients with SCD. The assessment of MND could thus provide useful information for AD risk stratification and enrichment in SCD samples. Importantly, SCD patients still have an increased risk for cognitive decline in the absence of MND.