Dementia has many causes, and the underlying disease determines the pattern of cognitive impairment, associated symptoms and progression. The most common causes in older adults include Alzheimer's disease, vascular brain disease, dementia with Lewy bodies and frontotemporal dementia, with mixed pathologies also frequent. Other neurological, infectious, inflammatory, metabolic and traumatic conditions can produce dementia or dementia-like cognitive syndromes. Dementia therefore cannot be attributed to one universal mechanism. At a biological level, causes include progressive neurodegeneration, abnormal accumulation of proteins, loss of neurons and synapses, vascular injury, disruption of white-matter networks, inflammation and other forms of brain dysfunction. Some causes are irreversible, while others may be treatable or partly reversible.
Alzheimer's disease is a major cause of dementia and is characterised biologically by abnormal accumulation of amyloid-beta plaques and tau protein pathology, together with synaptic dysfunction, neuronal loss and progressive network degeneration. Amyloid plaques consist primarily of aggregated amyloid-beta peptides outside neurons, while tau pathology involves abnormal forms of the tau protein accumulating within neurons and forming neurofibrillary tangles. These pathological processes are associated with disruption of communication between neurons and eventual neuronal and brain-tissue loss. Alzheimer's disease does not affect every brain region equally at the same time. Memory-related medial temporal structures are commonly affected early, followed by broader cortical networks as disease progresses. Genetic, biological and environmental factors influence susceptibility and disease development.
Vascular cognitive impairment and vascular dementia result from cerebrovascular disease that damages brain tissue or disrupts the networks supporting cognition. Large strokes can produce cognitive impairment when they affect strategically important regions, while multiple smaller infarcts can accumulate damage. Small-vessel disease can produce white-matter changes, lacunar infarcts and microscopic injury that interfere with communication between brain regions. Risk factors include hypertension, diabetes, smoking, high cholesterol, atrial fibrillation and other cardiovascular or cerebrovascular conditions. Vascular and Alzheimer's pathology frequently coexist, particularly in older adults, so cognitive decline may reflect combined neurodegenerative and vascular injury rather than one isolated disease process.
Dementia with Lewy bodies is associated with abnormal accumulation of alpha-synuclein in neuronal structures called Lewy bodies and Lewy neurites. It belongs to the broader group of synucleinopathies that also includes Parkinson's disease. Dementia with Lewy bodies commonly involves fluctuating attention and alertness, recurrent well-formed visual hallucinations, REM sleep behaviour disorder and parkinsonian motor features, although the exact combination varies. The underlying pathology can affect widespread brain networks, including systems involved in cognition, movement, sleep and autonomic function. Lewy body pathology can also coexist with Alzheimer's pathology, making clinical distinction more complex in some individuals.
Frontotemporal dementia refers to a group of disorders involving degeneration that particularly affects frontal and anterior temporal brain regions. Unlike typical Alzheimer's disease, early symptoms can centre on behaviour, personality, social conduct, executive function or language. Several pathological proteins can underlie frontotemporal degeneration, including abnormal tau or TDP-43, and some cases are associated with inherited genetic mutations. Mutations involving genes such as C9orf72, GRN and MAPT account for substantial proportions of familial frontotemporal dementia and related motor-neurone or neurological syndromes. The term therefore describes a clinical and anatomical syndrome with several possible molecular causes rather than one single disease mechanism.
Other conditions can produce cognitive decline that resembles dementia or can contribute to a dementia syndrome. Huntington's disease causes progressive neurological and cognitive impairment through an inherited mutation affecting the HTT gene. Prion diseases such as Creutzfeldt-Jakob disease can produce rapidly progressive dementia through abnormal prion protein folding. Severe traumatic brain injury can produce long-term cognitive impairment, and repeated head trauma has been associated with chronic traumatic encephalopathy in specific exposure contexts. Certain infections, autoimmune encephalitis, brain tumours, hydrocephalus, severe nutritional deficiencies and endocrine or metabolic disorders can also cause substantial cognitive impairment. Some of these conditions require urgent treatment because the underlying process may be modifiable.
Dementia risk is influenced by age, genetics, cardiovascular health, education and other life-course factors, but risk factors are not equivalent to direct causes in an individual. Increasing age is the strongest known risk factor for most common neurodegenerative dementias, although dementia is not an inevitable consequence of ageing. The APOE gene, particularly the APOE ε4 variant, is an important genetic risk factor for late-onset Alzheimer's disease but does not determine with certainty whether an individual will develop the disease. Rare mutations in genes such as APP, PSEN1 and PSEN2 can cause autosomal-dominant early-onset Alzheimer's disease. Similarly, genetic variants can substantially increase the risk of particular frontotemporal disorders.
Determining the cause of dementia requires examining the timing and pattern of cognitive decline, neurological features, medical history, medications, family history and relevant investigations. Brain MRI or CT can identify strokes, vascular disease, tumours, hydrocephalus and patterns of atrophy. Blood tests can identify metabolic, nutritional or systemic contributors. In selected cases, cerebrospinal-fluid biomarkers, amyloid or tau PET imaging, genetic testing or other specialised investigations can provide evidence for a specific neurodegenerative disease.
Mixed pathology is common, so a diagnosis may involve more than one contributing process. Consequently, "what causes dementia?" has no single answer: dementia arises when disease or injury sufficiently disrupts the neural systems required for cognition and independent functioning, and the specific cause must be determined from the individual's clinical and biological evidence.
