Subjective Cognitive Decline Shows Potential as Indicator for Amyloid Positivity

Olin Janssen, PhD

Findings from the Amyloid Biomarker Study cohort showed large variability in terms of amyloid positivity between elders with subjective cognitive decline (SCD), however, these SCD-specific characteristics may facilitate identifying amyloid-positive persons.

To build on the evidence of characteristics for individuals with SCD, lead author Olin Janssen, PhD, department of neurology, Maastricht University, and colleagues investigated associations of SCD-specific characteristics—including informant confirmation, domain-specific complains, concerns, and feelings of worse performance—with amyloid positivity. They also collected data on demographics, setting, apolipoprotein E (APOE) ε4 carriership, and neuropsychiatric symptoms.

The primary outcome measure was amyloid beta (Aß) deposition measured by PET or cerebrospinal fluid (CSF) biomarkers, dichotomized as normal and abnormal using study-specific cut-offs or upon visual read for PET. Among the 1640 participants with SCD (mean age, 66.8 [standard deviation (SD), 7.95 years) across 20 cohorts, 363 (21%) were amyloid positive.

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Janssen and her colleagues found considerable heterogeneity, as mean amyloid positivity estimated at age 70 ranged from 10% to 76%. In univariate analyses with Alzheimer disease (AD) risk factors, only older age (18% at age 60, 27% at age 70, and 39% at age 80; P <.001), a memory clinic setting (28% vs 17% for research setting; P = .008), and APOE ε4 carriership (37% vs 16% for APOE e4 noncarriers; P <.001) were associated with higher frequencies of amyloid positivity, whereas sex, education, and symptoms of depression and anxiety were not. A second multivariate analysis after adjusting for these found a higher frequency of amyloid positivity in persons with lower education.

The associations of informant confirmation of complaints, memory complaints, attention/concentration complaints, and depressive symptoms with amyloid positivity were found to be dependent on setting (P <.001 for informant confirmation of complaints, P <.001 for memory complaints, P <.001 for attention/concentration complaints, and P = .035 for depressive symptoms).

"Inclusion of practical, low-cost AD risk factors, and SCD-specific characteristics aids in the identification of individuals that will likely benefit from disease-modifying treatment," Janssen et al wrote. “However, the effect sizes of the SCD-specific characteristics were relatively small and of limited added value next to age, APOE ε4 carriership, and across settings."

Within a research setting, amyloid positivity was higher if complaints were confirmed by an informant (21% at age 70 years) compared to those without confirmation (8% at age 70 years) and higher in persons with complaints specific to memory (25% at age 70 years) compared to persons without complaints specific to memory (9% at age 70 years). Additionally, this continued in persons with complaints specific to attention/concentration (14% at age 70 years), and higher in persons without depressive symptoms (17% at age 70 years) compared to persons with depressive symptoms (8% at age 70 years).

Informant confirmation of complaints, memory complaints, attention/concentration complaints, and depressive symptoms were not associated with amyloid positivity for patients within a memory clinic setting.

The influence of feelings of worse performance were dependent on age (P = .005). In younger persons, feelings of worse performance were associated with a lower frequency of amyloid positivity (at age 50 years: 4% with feelings of worse performance vs 7% without feelings of worse performance; P = .017). In older persons, the opposite occurred, where feelings of worse performance were associated with a higher frequency of amyloid positivity (at age 90: 68% with feelings of worse performance vs 50% without feelings of worse performance; P = .021).

"Because it has been suggested previously that consistency over time of SCD characteristics is associated with a greater risk of future decline, the longitudinal relationship between SCD characteristics with amyloid and other AD biomarkers, as well as associations with clinical progression are important areas for future research," the study authors wrote. "Future research might also examine this longitudinal relationship in individuals with evidence of both amyloidosis and tauopathy, since these individuals might be at increased risk of clinical progression."

REFERENCE

Janssen O, Jansen WJ, Vos SJB, et al. Characteristics of subjective cognitive decline associated with amyloid positivity. Alzheimers Dement. Published December 8, 2021. doi:10.1002/alz.12512