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J Alzheimers Dis ; 100(1): 193-205, 2024.
Article in English | MEDLINE | ID: mdl-38848176

ABSTRACT

Background: The NIA-AA Research Framework on Alzheimer's disease (AD) proposes a transitional stage (stage 2) characterized by subtle cognitive decline, subjective cognitive decline (SCD) and mild neurobehavioral symptoms (NPS). Objective: To identify participant clusters based on stage 2 features and assess their association with amyloid positivity in cognitively unimpaired individuals. Methods: We included baseline data of N = 338 cognitively unimpaired participants from the DELCODE cohort with data on cerebrospinal fluid biomarkers for AD. Classification into the AD continuum (i.e., amyloid positivity, A+) was based on Aß42/40 status. Neuropsychological test data were used to assess subtle objective cognitive dysfunction (OBJ), the subjective cognitive decline interview (SCD-I) was used to detect SCD, and the Neuropsychiatric Inventory Questionnaire (NPI-Q) was used to assess NPS. A two-step cluster analysis was carried out and differences in AD biomarkers between clusters were analyzed. Results: We identified three distinct participant clusters based on presented symptoms. The highest rate of A+ participants (47.6%) was found in a cluster characterized by both OBJ and SCD. A cluster of participants that presented with SCD and NPS (A+:26.6%) and a cluster of participants with overall few symptoms (A+:19.7%) showed amyloid positivity in a range that was not higher than the expected A+ rate for the age group. Across the full sample, participants with a combination of SCD and OBJ in the memory domain showed a lower Aß42/ptau181 ratio compared to those with neither SCD nor OBJ. Conclusions: The cluster characterized by participants with OBJ and concomitant SCD was enriched for amyloid pathology.


Subject(s)
Alzheimer Disease , Amyloid beta-Peptides , Biomarkers , Cognitive Dysfunction , Neuropsychological Tests , Peptide Fragments , Humans , Male , Female , Amyloid beta-Peptides/cerebrospinal fluid , Amyloid beta-Peptides/metabolism , Aged , Cognitive Dysfunction/cerebrospinal fluid , Cognitive Dysfunction/psychology , Cognitive Dysfunction/diagnosis , Biomarkers/cerebrospinal fluid , Peptide Fragments/cerebrospinal fluid , Alzheimer Disease/cerebrospinal fluid , Alzheimer Disease/psychology , Alzheimer Disease/diagnosis , Middle Aged , Cohort Studies , Aged, 80 and over , Cluster Analysis
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