Abstract


Dementia encompasses a group of progressive neurodegenerative disorders marked by cognitive, behavioural, and functional decline, underpinned by complex neurobiological processes. This chapter outlines the anatomical, cellular, and molecular mechanisms that drive disease onset and progression. Structural vulnerability of the hippocampus, cerebral cortex, white matter, and cognitive networks underlies characteristic clinical manifestations. At the microscopic level, neuro-inflammation, mitochondrial dysfunction, oxidative stress, excitotoxicity, impaired protein clearance, and synaptic loss converge to promote neuronal injury. Distinct proteinopathies—including amyloid- plaques and tau tangles in Alzheimer’s disease, -synuclein inclusions in Lewy body dementia, and TDP-43 or tau aggregates in frontotemporal lobar degeneration—define specific dementia subtypes, yet share overlapping cascades of pathology. Vascular contributions, such as ischemia, hypoperfusion, and blood–brain barrier disruption, further compound neuronal vulnerability, highlighting the prevalence of mixed dementias. Collectively, these mechanisms illustrate dementia as a multifactorial disorder of network disintegration and cellular stress. Advancing insights into these processes are driving the development of biomarkers and disease-modifying therapies, paving the way for more precise, personalized approaches to diagnosis and care.