Timely and accurate assessment of cognitive impairment is a major unmet need in populations at risk. Alterations in speech and language can be early predictors of Alzheimer's disease and related dementias (ADRD) before clinical signs of neurodegeneration. Voice biomarkers offer a scalable and non-invasive solution for automated screening. However, the clinical applicability of machine learning (ML) remains limited by challenges in generalisability, interpretability, and access to patient data to train clinically applicable predictive models. Using DementiaBank recordings (N=291, 64% female), we evaluated ML techniques for ADRD screening and severity prediction from spoken language. We validated model generalisability with pilot data collected in-residence from older adults (N=22, 59% female). Risk stratification and linguistic feature importance analysis enhanced the interpretability and clinical utility of predictions. For ADRD classification, a Random Forest applied to lexical features achieved a mean sensitivity of 69.4% (95% confidence interval (CI) = 66.4-72.5) and specificity of 83.3% (78.0-88.7). On real-world pilot data, this model achieved a mean sensitivity of 70.0% (58.0-82.0) and specificity of 52.5% (39.3-65.7). For severity prediction using Mini-Mental State Examination (MMSE) scores, a Random Forest Regressor achieved a mean absolute MMSE error of 3.7 (3.7-3.8), with comparable performance of 3.3 (3.1-3.5) on pilot data. Linguistic features associated with higher ADRD risk included increased use of pronouns and adverbs, greater disfluency, reduced analytical thinking, lower lexical diversity and fewer words reflecting a psychological state of completion. Our interpretable predictive modelling offers a novel approach for in-home integration with conversational AI to monitor cognitive health and triage higher-risk individuals, enabling earlier detection and intervention.

We consider the theoretical constraints on interactions between coupled cortical columns. Each column comprises a set of neural populations, where each population is modelled as a neural mass. The existence of semi-stable states within a cortical column has been shown to be dependent on the type of interaction between the constituent neuronal subpopulations, i.e., the form of the implicit synaptic convolution kernels. Current-to-current coupling has been shown, in contrast to potential-to-current coupling, to create semi-stable states within a cortical column. In this analytic and numerical study, the interaction between semi-stable states is characterized by equations of motion for ensemble activity. We show that for small excitations, the dynamics follow the Kuramoto model. However, in contrast to previous work, we derive coupled equations between phase and amplitude dynamics. This affords the possibility of defining connectivity as a dynamic variable. The turbulent flow of phase dynamics found in networks of Kuramoto oscillators indicate turbulent changes in dynamic connectivity for coupled cortical columns. Crucially, this is something that has been recorded in epileptic seizures. We used the results we derived to estimate a seizure propagation model, which allowed for relatively straightforward inversions using variational Laplace (a.k.a., Dynamic Causal Modelling). The face validity of the ensuing seizure propagation model was established using simulated data as a prelude to future work; which will investigate dynamic connectivity from empirical data. This model also allows predictions of seizure evolution, induced by virtual lesions to synaptic connectivity: something that could be of clinical use, when applied to epilepsy surgical cases.