Clinical Manifestations

People living with early-onset Alzheimer's disease (EOAD) are often misdiagnosed or experience delays in diagnoses due to their young age of onset, non-amnestic presentation, and rapid clinical progression. Brief digital cognitive measures may be a valuable and scalable alternative to traditional tests for early detection of EOAD. We examined the associations of the UCSF Tablet-based Cognitive Assessment Tool (TabCAT) tests with clinical and pathophysiologic markers of AD in the multisite Longitudinal Early Onset Alzheimer's Disease Study.

83 cognitively unimpaired controls and 392 patients with a clinical diagnosis of EOAD (MCI or mild dementia) underwent TabCAT testing, including 2 tests of executive function/attention (Match, Flanker) and 2 visuospatial tests (Line Length and Line Orientation; Figure 1A). First, we assessed correlations between TabCAT scores and classic pen-and-paper tests in the whole cohort using ranked coefficients. Second, we used receiver operating characteristic analyses to examine each cognitive score's ability to distinguish between Aβ- (n = 95) and Aβ+ (n = 297) clinically impaired patients, as defined by a quantification-aided visual read of Florbetaben-PET. We then investigated regional associations between TabCAT scores and Flortaucipir (tau)-PET using voxel-wise analyses in the Aβ+ patients.

In the whole cohort, Match and Flanker were associated with all pen-and-paper tests, with strongest correlations observed with the MMSE, MoCA, and Trails A (r's >0.7). As expected, Line Length and Line Orientation tests showed strongest correlations (r's >0.4) with traditional tasks that rely on visuospatial skills: Benson Figure Copy and Trails A (Figure 1B). Of TabCAT tests, Match best discriminated Aβ+ from Aβ- patients (Area Under the Curve (AUC)=0.82), outperforming the MMSE (AUC=0.75) and MoCA (AUC=0.75), and comparable to the overall best performing test Benson Figure Recall (AUC=0.85; Figure 2). In Aβ+ patients, Match and Flanker correlated with tau-PET signal in most cortical areas, especially dorsal frontal and parietal areas. The Line tests were specifically associated with occipital tau-PET signal (Figure 3).

In this large multisite study, TabCAT measures show good concurrent validity and associations with pathophysiological markers of AD: Aβ-PET positivity and neuroanatomical specific patterns of tau-PET. These digital measures have promise for frontline identification and early diagnosis of patients with EOAD.