The brain illustration shows the six main regions affected by Alzheimer's disease — each coloured differently. The pulsing red circles mark the hippocampus — the first region damaged, responsible for forming new memories. Click any region to learn what it does and how Alzheimer's affects it.

Caused by two abnormal protein deposits: amyloid-beta plaques forming between neurons and tau tangles forming inside neurons. Together they disrupt synaptic communication, trigger neuroinflammation, and cause neuronal death — beginning in the hippocampus and entorhinal cortex 15–20 years before any symptom appears.

• 🔁 Repetitive questioning — each answer is forgotten immediately
• 📅 Disorientation to time, date, year, or even decade
• 💬 Word-finding difficulty (anomia) — pausing, using wrong words
• 🗺️ Getting lost in familiar places — spatial map dissolves
• 💰 Financial management failure — bills, susceptibility to scams
• 🪞 Anosognosia — up to 80% unaware of their own deficits
• 🌙 Sundowning — increased confusion in late afternoon and evening

Caused by brain damage from strokes, TIAs, or small vessel disease — white matter lesions and lacunar infarcts. Unlike Alzheimer's, decline is often stepwise: stable periods punctuated by sudden drops after vascular events. Executive dysfunction and gait problems frequently precede memory loss — the key distinguishing feature from Alzheimer's. What protects the heart protects the brain.

• ⚡ Sudden cognitive decline after stroke — stepwise, not gradual like AD
• 🎯 Executive dysfunction first — planning fails before memory loss
• 🚶 Gait disturbance — often the first sign of small vessel disease
• 😐 Apathy and depression — more severe and prominent than in AD
• 🔀 Fluctuating cognition — good days and bad days
• 😤 Emotional lability — crying or laughing disproportionately (pseudobulbar affect)

Caused by alpha-synuclein protein aggregating into Lewy body inclusions inside neurons. Forms a spectrum with Parkinson's Disease Dementia (PDD) — in DLB, cognitive symptoms appear first or simultaneously with motor symptoms; in PDD, motor symptoms precede dementia by more than one year. Both share identical Lewy body pathology.

• 👻 Vivid visual hallucinations — detailed people, animals, objects. Present in 80% of DLB. Defining feature.
• 🌊 Fluctuating cognition — alert one hour, profoundly confused the next
• 🚶 Parkinsonism — rigidity, bradykinesia, shuffling gait
• 😴 REM Sleep Behaviour Disorder (RBD) — acting out dreams. Often the FIRST sign, 10–15 years before dementia diagnosis
• ⬇️ Severe autonomic dysfunction — fainting, constipation, urinary urgency
• ⚠️ Antipsychotic hypersensitivity — potentially fatal

Neurodegeneration of frontal and temporal lobes — the regions controlling personality, behaviour, judgment, and speech. NOT primarily a memory disease in early stages — this leads to frequent misdiagnosis as depression, bipolar disorder, or OCD. Three variants: behavioural (bvFTD — personality/behaviour), Progressive Nonfluent Aphasia (PNFA — speech production), and Semantic Dementia (SD — loss of word meanings).

• 😈 Disinhibition — inappropriate remarks, shoplifting without remorse, loss of social filters
• 😶 Profound apathy — complete loss of motivation; no distress about inaction
• 🔄 Compulsive repetitive behaviours — rigid routines, hoarding, tapping; mistaken for OCD
• 🍔 Dietary changes — sudden craving for sweets, gorging on food
• 💝 Loss of empathy — cannot feel others' pain; appears callous or psychopathic to family
• 🗣️ Language collapse — PNFA: effortful speech; SD: loss of word meanings ("what is a penguin?")
• ✅ Memory relatively preserved early — the main reason for missed diagnosis

Caused by excess cerebrospinal fluid (CSF) accumulating in brain ventricles — compressing surrounding white matter. The classic triad appears in order: (1) gait disturbance first — the "magnetic gait" where feet appear stuck to the floor; (2) urinary incontinence second; (3) cognitive decline third. VP shunt surgery can dramatically reverse or halt decline — often within days of the procedure.

The gait in NPH is clinically distinctive: wide-based, shuffling, slow — feet appear literally "stuck" or "magnetic" to the floor. It resembles Parkinson's disease but appears before cognitive symptoms in 70% of NPH cases. The shuffling gait is the most important clinical clue and the first symptom to look for.

Caused by repeated head impacts — not necessarily concussions, but the thousands of subconcussive hits that never cause immediate symptoms but cumulatively destroy the brain. The tau pathology resembles Alzheimer's but distributes differently: perivascularly in the depths of sulci (cortical folds) rather than spreading from the hippocampus outward. Currently can only be definitively confirmed at autopsy.

• 😠 Mood first (30s–40s) — depression, irritability, explosive anger; misdiagnosed as PTSD
• 🧠 Cognition second — memory problems, executive dysfunction, slowed processing
• 💔 Suicidality — dramatically elevated risk; Junior Seau, Dave Duerson
• 💊 Substance abuse — self-medication of pain and depression
• ⚡ Impulsivity and violence — often directed at family members
• 🔍 10–30 year latency — cause and effect invisible to individuals in youth

When established Parkinson's Disease develops significant dementia — cognitive symptoms appearing more than 1 year after motor symptom onset. Both PDD and DLB share identical alpha-synuclein Lewy body pathology. Characterised by executive dysfunction, attention failure, visuospatial problems, and hallucinations — rather than the profound amnesia of Alzheimer's.

• 🧩 Executive function failure — planning, organising, multitasking
• 👻 Visual hallucinations — detailed people and animals
• 😴 REM Sleep Behaviour Disorder — acting out dreams
• ⬇️ Orthostatic hypotension — dizziness on standing, falls
• 😔 Depression and anxiety — present in 40–60%
• 🔍 Attention breakdown before memory loss

Mixed dementia occurs when a person has more than one type of dementia pathology simultaneously. The most common combination is Alzheimer's disease pathology (amyloid plaques and tau tangles) alongside vascular damage (white matter lesions, lacunar infarcts). This is found at autopsy in approximately 50% of all dementia cases — meaning the single diagnosis most people receive during life understates the true complexity of what is happening in the brain.

Korsakoff syndrome is caused by severe thiamine (Vitamin B1) deficiency — most commonly from chronic heavy alcohol use, which both reduces thiamine intake and impairs thiamine absorption. It damages the mammillary bodies and thalamus — structures critical for memory formation. The defining feature is confabulation: the person unconsciously invents detailed, plausible memories to fill the gaps — they are not lying, they genuinely believe their fabricated accounts.

• 🕳️ Severe anterograde amnesia — cannot form any new memories
• 📖 Confabulation — invents detailed false memories without knowing it
• 👀 Eye movement abnormalities — nystagmus, gaze palsy
• 🚶 Ataxia — unsteady gait, coordination problems
• 😶 Apathy and flat affect — little emotional response
• 🔙 Retrograde amnesia — gaps in memories from years before onset

• ⚡ Rapidly progressive dementia — weeks not years
• 🤸 Myoclonus — sudden involuntary muscle jerks, often startle-triggered
• 👁️ Visual disturbances and hallucinations
• 🚶 Cerebellar ataxia — severe coordination failure
• 😴 Akinetic mutism in late stages — awake but unresponsive
• 🧠 Characteristic MRI findings — cortical ribboning, basal ganglia signal

PCA is a syndrome — most commonly caused by Alzheimer's pathology — in which neurodegeneration targets the posterior brain regions (parietal, occipital, posterior temporal cortices) rather than the hippocampus first. The result is devastating: the person loses the ability to read, write, drive, navigate space, recognise objects by sight, and calculate — while their episodic memory and verbal fluency may remain largely intact for years. It is profoundly under-diagnosed because clinicians do not expect Alzheimer's in a 57-year-old who still knows what year it is.

• 📖 Cannot read — letters visible but uninterpretable (alexia)
• ✍️ Cannot write legibly — visuomotor coordination fails (agraphia)
• 🚗 Driving becomes impossible — cannot judge distances or read signs
• 🪒 Cannot use familiar tools — dressing apraxia
• 🔢 Arithmetic fails — cannot read a clock face (acalculia)
• 🖼️ Object agnosia — cannot recognise objects by sight, only by touch
• ✅ Memory relatively preserved early — the main diagnostic confusion
• 😰 Severe anxiety — living in a world that no longer makes visual sense

Every person with Down syndrome has three copies of chromosome 21, which carries the APP (amyloid precursor protein) gene. This causes lifelong overproduction of amyloid-beta protein — on average 1.5× normal levels from birth. Amyloid plaques begin forming in the brain during adolescence — 30+ years before any dementia symptoms. By age 40, virtually all individuals with Down syndrome have full Alzheimer's pathology on PET scan. Most develop clinical dementia between ages 50–65. Down syndrome is therefore the most penetrant genetic model of Alzheimer's disease in the world.