Apraxia and the Progressive Loss of Functional Integration in Alzheimer’s Disease: A Neurocognitive Framework

Alzheimer’s disease is biologically defined by beta-amyloid and tau pathology, yet the mechanisms through which molecular and network alterations become expressed as the progressive loss of meaningful behaviour remain incompletely understood. This perspective proposes a neurocognitive framework in which apraxia provides a particularly informative clinical window onto the deterioration of functional integration. The model assigns a central organisational role to interhemispheric communication within distributed frontoparietal, temporal, language, memory, and default mode networks. It interprets recognised apraxic syndromes as clinically distinct disturbances that expose complementary requirements of meaningful action, including action knowledge, bodily configuration, sequencing, spatial organisation, object use, fine motor control, and interhemispheric transfer. The framework further examines whether partially convergent impairments of gesture, connected speech, autobiographical construction, and perspective coordination may reflect declining capacity to integrate specialised representations within coherent behaviour. Its original theoretical component proposes that conscious proprioceptive organisation contributes to maintaining body-centred reference frames through which heterogeneous information is coordinated during action and perspective transformation. Evidence for Alzheimer-related connectivity alterations and impairments of praxis, discourse, and autobiographical memory is reviewed separately from the proposed integrative mechanism, which requires direct testing. The framework predicts that longitudinal changes across these behavioural domains will covary with deterioration in interhemispheric and large-scale network connectivity and provide explanatory information beyond global cognitive severity and regional atrophy. Multimodal longitudinal studies combining molecular biomarkers, neuroimaging, apraxia assessment, connected-speech analysis, and autobiographical tasks are proposed to evaluate, delimit, or reject these predictions.