Mayo‐PACC: A parsimonious preclinical Alzheimer's disease cognitive composite comprised of public‐domain measures to facilitate clinical translation

Abstract

Introduction We aimed to define a Mayo Preclinical Alzheimer's disease Cognitive Composite (Mayo‐PACC) that prioritizes parsimony and use of public domain measures to facilitate clinical translation. Methods Cognitively unimpaired participants aged 65 to 85 at baseline with amyloid PET imaging were included, yielding 428 amyloid negative (A‐) and 186 amyloid positive (A+) individuals with 7 years mean follow‐up. Sensitivity to amyloid‐related cognitive decline was examined using slope estimates derived from linear mixed models (difference in annualized change across A+ and A‐ groups). We compared differences in rates of change between Mayo‐PACC and other composites (A+ > A‐ indicating more significant decline in A+). Results All composites showed sensitivity to amyloid‐related longitudinal cognitive decline (A+ > A‐ annualized change p < 0.05). Comparisons revealed that Mayo‐PACC (AVLT sum of trials 1‐5+6+delay, Trails B, animal fluency) showed comparable longitudinal sensitivity to other composites. Discussion Mayo‐PACC performs similarly to other composites and can be directly translated to the clinic.

Comparing Cognitive Tests and Smartphone‐Based Assessment in 2 US Community‐Based Cohorts

“…Other studies examining associations between digital cognitive tasks and traditional paper and pencil tests have generally found moderate to high associations between the 2. 39 , 40 , 41 , 42 A major benefit of DANA is that it can be self‐administered remotely or in the clinic. 31 , 43 Recent articles have emphasized the need for urgently incorporating cognitive testing via digital testing in clinical practice using standardized procedures.…”

Continuous Associations Between Remote Self-Administered Cognitive Measures and Imaging Biomarkers of Alzheimer’s Disease

“…First, the Mayo Clinic Preclinical Alzheimer's Cognitive Composite (Mayo-PACC) is an average of z-scores from the AVLT sum of trials, Trail Making Test B (reversed) and animal fluency. 14 Second, a Global z-score was calculated as the average of z-scores from all nine neuropsychological tests; this is routinely used in MCSA publications (see Stricker et al 14 for comparison to several PACCs). Like for MTD-SBCz, both Mayo-PACC and Global-z composites were calculated using participants from the full sample available at the time of this analyses (participants with and without available neuroimaging) as the reference group.…”

“…Currently, PACCs rely on z-scores that are study specific, where z-scores are typically referenced to the sample presented within the study, making interpretation of performance across studies more challenging. [14][15][16] By contrast, in the current study we introduce an MTD raw composite score that can allow MTD to function like a Mini Mental Status Exam (MMSE) or Montreal Cognitive Assessment (MoCA). A raw score composite will facilitate development of easily understood and generalizable cut-offs that do not adjust away the effects of age, which is highly confounded with increased prevalence of AD biomarkers and other undetected neuropathologies 17,18 and thereby decreases sensitivity to mild cognitive impairment (MCI).…”

Maximizing utility of neuropsychological measures in sex‐specific predictive models of incident Alzheimer's disease in the Framingham Heart Study

“…There is therefore an urgent and unmet need for sensitive NP screening tools. [17][18][19] Sex differences in NP tests have not been thoroughly harnessed despite numerous studies reporting them. In a study of MCI, given equal levels of hippocampal atrophy, women present with relatively preserved verbal memory compared to men.…”

“…The ability to identify individuals with seemingly normal test scores who progress to AD is crucial for preventative strategies, early initiation of clinical interventions, and patient selection for clinical trials. There is therefore an urgent and unmet need for sensitive NP screening tools 17–19 …”