Dementia / Alzheimer's disease
Also known as: dementia, Alzheimer's disease, AD, neurocognitive disorder, major neurocognitive disorder
Dementia is a syndrome of progressive cognitive decline severe enough to impair daily life; Alzheimer's disease is its most common cause, characterised by amyloid plaques, tau tangles, and gradual neurodegeneration.
A note on scope: This entry is informational — it describes what dementia and Alzheimer's disease are in the context of brain ageing research. It is not a diagnostic tool, and nothing here should be used to draw conclusions about any individual's health. Diagnosis requires clinical evaluation by a qualified professional.
Dementia
Dementia is a clinical syndrome — a collection of symptoms — rather than a single disease. It describes progressive decline in two or more cognitive domains (memory, language, attention, executive function, visuospatial skills) that is severe enough to interfere with daily life, and that represents a change from a previous level of functioning.
Dementia has many causes:
| Type | Approximate share of cases |
|---|---|
| Alzheimer's disease | ~60–70% |
| Vascular dementia | ~15–20% |
| Lewy body dementia | ~5–10% |
| Frontotemporal dementia (FTD) | ~5–10% |
| Mixed pathology | Common, particularly in older adults |
Alzheimer's disease
Alzheimer's disease (AD) is the most common neurodegenerative cause of dementia. Its defining neuropathological features are:
- Amyloid-β plaques — extracellular deposits of misfolded amyloid-β protein, particularly in regions of the default mode network
- Neurofibrillary tangles — intracellular accumulations of hyperphosphorylated tau protein, initially in the hippocampus and entorhinal cortex, spreading outward with disease progression
- Neurodegeneration — progressive loss of synapses and neurons, reflected on MRI as characteristic atrophy beginning in medial temporal structures
Importantly, these pathological changes begin 15–25 years before clinical symptoms. There is now a well-developed biological staging system (the amyloid/tau/neurodegeneration, or AT(N) framework) that defines Alzheimer's disease by its biology rather than its clinical presentation.
The continuum from ageing to dementia
Alzheimer's disease and normal brain ageing exist on a continuum. Both involve gradual cortical thinning, memory-related network changes, and increased CSF biomarker concentrations — but at different rates and magnitudes. This is one reason brain age models, which learn the typical rate of structural change in healthy ageing, produce larger brain age gaps in people who go on to develop dementia — sometimes years before diagnosis.
Intermediate stages include:
- Subjective cognitive decline (SCD) — self-reported memory concerns without objective impairment
- Mild cognitive impairment (MCI) — objective cognitive decline not yet affecting daily function; roughly 10–15% per year progress to dementia
Risk and protective factors
Established modifiable risk factors for dementia (Lancet Commission, updated 2024) include:
- Hearing loss, depression, social isolation, physical inactivity
- Hypertension, obesity, diabetes, smoking, excessive alcohol
- Traumatic brain injury, air pollution
Protective factors include those that build cognitive reserve: education, social engagement, cognitive activity, aerobic exercise.
The single largest non-modifiable risk factor is age; the APOE ε4 allele is the most common genetic risk factor.
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Related terms
Atrophy
The loss of brain tissue volume or cortical thickness over time, reflecting a reduction in the size or number of neurons and their supporting cells.
Brain age gap
The difference between brain age and chronological age. A positive gap means the brain looks older than it should; a negative gap, younger.
Cognitive reserve
The brain's accumulated resilience against pathology — built over a lifetime through education, cognitive engagement, and social activity — which allows some people to sustain function despite significant structural brain changes.
Glymphatic system
A brain-wide network of fluid channels, driven largely during sleep, that clears metabolic waste — including proteins linked to neurodegeneration — from brain tissue.
Default mode network
A set of brain regions that are most active when the mind is at rest and not focused on an external task — linked to self-referential thinking, memory retrieval, and mind-wandering.
Cerebrospinal fluid
The clear fluid that surrounds and cushions the brain and spinal cord, circulates through the ventricles, and plays a key role in waste clearance from the brain.