Feasibility of real world end‐points of functional neurophysiology in Alzheimer’s disease dementia

Abstract

AbstractBackgroundClinic‐based biomarkers are effective in tracking disease progression in clinical research, but do not scale to support public health needs or large‐scale real‐world studies. Purely digital markers are scalable but lack the objectivity and neurobiological grounding of clinical measures. These first results of a real‐world feasibility study demonstrate that objective measures of a range of domains including EEG (Figure 1) are user‐friendly and suitable for repeated at‐home use by patients and older controls.Method60 patients and 60 matched controls are being recruited for a 1‐year repeated sampling study in the UK. Patients were clinically assessed to have mild Alzheimer’s type dementia. Participants were asked to complete about 30 minutes of behavioral tasks including memory, executive function, affective processing and language, while synchronized EEG was recorded using a self‐applied dry‐sensor headset. This interim data is from an initial 2‐week burst sampling period, for the first half of the cohorts.ResultAdherence was 76% for the dementia group (N = 29, mean age = 75; ADAS = Cog 24.3) and 88% for the control group (N = 36, mean age = 71; ADAS = Cog 7.8). A symbol substitution task (executive function) differentiated strongly between groups (t(53) = 6.9), and correlated highly with a conventional pen‐and‐paper DSST benchmark (rho = 0.79). An associative memory task also patterned strongly with disease status (t(54) = 5.7) and correlated with the Verbal Paired Associates benchmark (rho = 0.76). The grand average P300 ERP, elicited by a gamified 2‐stimulus oddball task, showed characteristic features of sensory and higher cognitive processing (Figure 2). As expected in the patient group, the P300 was reduced and delayed; and the resting‐state EEG theta and alpha power were enhanced and reduced, respectively. Radar plots (Figure 3), illustrate the pattern observed across domains in one representative Alzheimer’s patient and one control. Data from a fronto‐temporal dementia sister study is included for comparison.ConclusionInterim data from this first‐in‐class study suggest that patients with mild Alzheimer’s disease dementia are capable and willing to participate in intensive home‐based functional neurophysiology studies, if technology is designed to be engaging and easy to use. Initial examination of the data aligns with established benchmarks, constituting positive early evidence for construct validity and technical feasibility.