Is comprehensiveness critical? Comparing short and long format cognitive assessments in preclinical Alzheimer disease

Abstract

Background Comprehensive testing of cognitive functioning is standard practice in studies of Alzheimer disease (AD). Short-form tests like the Montreal Cognitive Assessment (MoCA) use a “sampling” of measures, administering key items in a shortened format to efficiently assess cognition while reducing time requirements, participant burden, and administrative costs. We compared the MoCA to a commonly used long-form cognitive battery in predicting AD symptom onset and sensitivity to AD neuroimaging biomarkers. Methods Survival, area under the receiver operating characteristic (ROC) curve (AUC), and multiple regression analyses compared the MoCA and long-form measures in predicting time to symptom onset in cognitively normal older adults (n = 6230) from the National Alzheimer’s Coordinating Center (NACC) cohort who had, on average, 2.3 ± 1.2 annual assessments. Multiple regression models in a separate sample (n = 416) from the Charles F. and Joanne Knight Alzheimer Disease Research Center (Knight ADRC) compared the sensitivity of the MoCA and long-form measures to neuroimaging biomarkers including amyloid PET, tau PET, and cortical thickness. Results Hazard ratios suggested that both the MoCA and the long-form measures are similarly and modestly efficacious in predicting symptomatic conversion, although model comparison analyses indicated that the long-form measures slightly outperformed the MoCA (HRs > 1.57). AUC analyses indicated no difference between the measures in predicting conversion (DeLong’s test, Z = 1.48, p = 0.13). Sensitivity to AD neuroimaging biomarkers was similar for the two measures though there were only modest associations with tau PET (rs = − 0.13, ps < 0.02) and cortical thickness in cognitively normal participants (rs = 0.15–0.16, ps < 0.007). Conclusions Both test formats showed weak associations with symptom onset, AUC analyses indicated low diagnostic accuracy, and biomarker correlations were modest in cognitively normal participants. Alternative assessment approaches are needed to improve how clinicians and researchers monitor cognitive changes and disease progression prior to symptom onset.

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Development of a smartphone screening test for preclinical Alzheimer’s disease and validation across the dementia continuum

“…Across the disease continuum, there are three key stages of AD pathology: preclinical AD (before any cognitive symptoms or signs emerge), Mild Cognitive Impairment (MCI), which is also called “prodromal AD” (where cognitive decline has occurred but not to the stage to impair functional abilities), and AD dementia. Cognitive tests commonly used clinically, such as the Montreal Cognitive Assessment (MoCA), and the Mini-Mental State Examination (MMSE), lack sensitivity until the MCI stage, when AD pathology has progressed for around 10 years [ 9 , 10 ]. Specialist biomarkers such as cerebrospinal fluid (CSF) tests and positron emission tomography (PET) brain scans can detect AD pathological changes across the continuum, including in preclinical AD, but are rarely used clinically as they are too expensive, inaccessible, or invasive and would not be suitable for population-level screening [ 11 ].…”

Development of a smartphone screening test for preclinical Alzheimer's disease and validation across the dementia continuum

“…Across the disease continuum, there are three key stages of AD pathology: preclinical AD (before any cognitive symptoms or signs emerge), Mild Cognitive Impairment (MCI), which is also called "prodromal AD" (where cognitive decline has occurred but not to the stage to impair functional abilities), and AD dementia. Cognitive tests commonly used clinically, such as the Montreal Cognitive Assessment (MoCA), and the Mini-Mental State Examination (MMSE), lack sensitivity until the MCI stage, when AD pathology has progressed for around 10 years (9,10). Specialist biomarkers such as cerebrospinal uid (CSF) tests and positron emission tomography (PET) brain scans can detect AD pathological changes across the continuum, including in preclinical AD, but are rarely used clinically as they are too expensive, inaccessible, or invasive and would not be suitable for population-level screening (11).…”