Symptomatic Clusters Related to Amyloid Positivity in Cognitively Unimpaired Individuals.

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 Aβ42/40 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 Aβ42/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.