A Comprehensive Review on Major Neurocognitive Disorders: Etiology, Pathophysiology, Clinical Features, Diagnosis, and Management

Abstract

Major Neurocognitive Disorders (MNDs), commonly referred to as dementia, are a heterogeneous group of progressive conditions characterized by a significant decline in cognitive function that interferes with independence in daily living. With increasing global life expectancy, the prevalence of MNDs particularly Alzheimer’s disease (AD) has risen markedly, posing a substantial clinical, social, and economic burden worldwide. MNDs arise from diverse etiologies, including neurodegenerative processes, cerebrovascular disease, genetic disorders, infections, metabolic abnormalities, substance or medication exposure, and traumatic brain injury, with mixed pathologies frequently observed in older adults. The underlying pathophysiology varies by subtype but often involves abnormal protein aggregation, synaptic dysfunction, neuroinflammation, and progressive neuronal loss. Alzheimer’s disease is characterized by amyloid-β plaque deposition, neurofibrillary tangles of hyperphosphorylated tau, and cortical atrophy, while other dementias exhibit distinct proteinopathies or vascular injury patterns. Clinically, MNDs present with progressive impairments in memory, executive function, language, attention, and visuospatial abilities, frequently accompanied by behavioural and psychological symptoms such as agitation, depression, hallucinations, and apathy. Diagnosis is primarily clinical, supported by cognitive assessment tools, laboratory investigations to exclude reversible causes, neuroimaging, and biomarker evaluation, although definitive diagnosis remains neuropathological. Current management strategies focus on symptomatic treatment, modification of risk factors, and comprehensive supportive care. Despite recent advances in disease-modifying therapies, MNDs remain incurable, underscoring the importance of early recognition, accurate diagnosis, and a multidisciplinary approach to care.