Awareness of cognitive decline and CSF‐biomarkers in memory clinic patients: Results from the DELCODE‐study

Abstract

AbstractBackgroundDecreased awareness of cognitive deficits is a common symptom of dementia. Less is known about the evolution of decreased awareness in earlier stages of Alzheimer’s Disease (AD). Recent studies using the discrepancy between self‐ and informant report found reduced awareness in many patients with mild cognitive impairment (MCI), but generally heightened awareness in cognitively normal individuals with Amyloid pathology. In memory clinic samples, patient and caregiver ratings of cognitive decline were associated with AD‐biomarkers. We investigated in the relationship between CSF‐biomarkers, informant ratings and reduced self‐awareness in a large memory‐clinic sample.MethodsWe analyzed data from n=323 patients with available CSF‐biomarkers (age=71.17; SD=5.71) from the DELCODE‐study (n=211 SCD‐patients; n=112 MCI‐patients). Cognitive complaints in five different domains were assessed using a self‐ and informant rated interview form (Miebach et al. 2019). Reduced self‐awareness was calculated using a self‐/informant discrepancy score. The relationship with CSF‐biomarker was examined using linear regression, controlling for demographic variables and objective memory performance. Participants were classified using the ATN‐system for the diagnosis of preclinical AD.ResultsAll patients reported a cognitive decline in at least 3 domains. On average, SCD participants had positive self‐awareness scores (M=1.20; SD=1.87), indicating more self‐ than informant reported decline, while this significantly reversed in MCI (M=‐.514; SD=1.67). In the total sample, the discrepancy was associated with CSF‐Aß‐42 (ß=.213; p<.000), CSF‐t‐Tau (ß=‐.163; p<.005) and CSF‐Aß/tau‐ratio (ß=.232; p<.001). This association was similar in SCD and MCI. Regarding Biomarker profiles, n=66 participants were classified as A+/T+, n=38 as A+/T‐; n=139 participants were classified as A‐T‐N‐ and n=80 as non‐AD‐pathologic change. Participants with an AD‐typical Biomarker profile (A+/T+) had significantly higher informant than self‐ratings of cognitive decline (p<.001) and reduced awareness (p<.003).ConclusionIn memory clinic patients, lower awareness (i.e. relatively less self‐ than informant rated complaints) was associated with CSF‐Aß‐42, t‐Tau and the Aß/tau‐ratio. The relationship with CSF‐Aß42 and Aß/tau ratio was independent from objective memory impairment, showing that in the absence of objective impairment (i.e. SCD stage) informant ratings of cognitive decline are particularly informative. Results support the use of informant ratings in memory clinic samples, and the inclusion of an informant confirmation in the SCD‐plus criteria, specifying which features increase the likelihood of AD‐pathology in SCD.