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Basic Neurosciences · Paper A

Alzheimer's disease: course and behavioural/psychological symptoms (BPSD)

The idea

Alzheimer's disease does not thin memory out evenly — it erases it from the newest memory backwards, and almost everything the exam asks about the course follows from that one direction of travel. New events stop being stored first, so a woman can describe her wedding in detail and not the conversation ten minutes ago. As the pathology spreads outwards from the medial temporal lobe into the association cortex, language, learned action and recognition fail in turn, which is why aphasia, apraxia and agnosia arrive as a cluster in the middle of the illness rather than at the start. Running alongside all of that, and often the reason a family stops coping, are the behavioural and psychological symptoms of dementia: apathy, depression, persecutory delusions, misidentification, wandering, agitation and disturbed sleep. Stage the person by what they can still do, and treat a sudden behavioural change as a search for a physical cause before it is anything else.

How it works

The order in which abilities are lost is set by the order in which the pathology spreads, and holding those two together is what turns a symptom list into a course. New episodic memories are laid down through the hippocampus and the surrounding medial temporal lobe, and over subsequent years they are consolidated into the wider cortex, so that a memory decades old no longer depends on the structure that first created it. Alzheimer's pathology reaches the medial temporal lobe early, which is why the earliest and most reliable failure is anterograde: the making of new memories stops, while memories consolidated long ago remain available. That produces the backwards gradient families describe, in which the oldest memories are the most resistant and the person can appear, at times, to be living in an earlier decade — a plausible reading, in a person whose most recent surviving memories genuinely are from that decade. As the disease spreads outwards into the association cortex, each newly affected region contributes its own deficit: temporal language cortex gives anomia and then a fuller aphasia, parietal cortex gives apraxia and agnosia, and involvement of the systems supporting perception and belief brings the delusions and misidentifications that cluster in the middle stage. Apathy is the commonest behavioural symptom of all across the illness, and depression tends to appear earlier, while insight is partly preserved and the person can still register what is happening. In the severe stage the accumulated cortical loss leaves the person mute, immobile, incontinent and unable to swallow safely, and death typically follows a complication of that state, most often bronchopneumonia after aspiration rather than the dementia itself.

How to spot it

Repeated questions and this morning's conversation already gone, while events from decades ago are recounted in detail: the mild stage of Alzheimer's disease.
Word-finding difficulty, trouble dressing despite normal power, and failure to recognise a familiar face together place a patient in the moderate stage.
When the family say she keeps accusing them of stealing her money or her belongings, that is the classic persecutory delusion of Alzheimer's disease, not a primary psychotic illness.
A person who talks to their own reflection as though it were a stranger is showing the mirror sign, a self-misidentification belonging to the moderate to severe stage.
Recurrent, well-formed visual hallucinations appearing early, with fluctuating attention and parkinsonism, are pointing away from Alzheimer's disease and towards dementia with Lewy bodies.
Marked deterioration over forty-eight hours in someone with known dementia reads as delirium on top of dementia, and the stem wants the physical cause.

Tell it apart

Alzheimer's disease vs dementia with Lewy bodies — hallucinations occur in both, but in dementia with Lewy bodies they are early, recurrent, well formed and accompanied by fluctuating attention and spontaneous parkinsonism, alongside severe sensitivity to antipsychotics.
Alzheimer's disease vs vascular dementia — Alzheimer's declines smoothly and continuously, while vascular dementia classically declines in steps against a background of vascular risk factors and focal neurological signs.
Alzheimer's disease vs Huntington's disease — Huntington's is autosomal dominant with chorea and mid-adult onset, and its dementia leads with executive and psychiatric change rather than with early episodic amnesia.
Alzheimer's disease vs depression presenting as cognitive impairment — depression gives a shorter, more datable history with prominent complaints of memory failure and "don't know" answers, and low mood that came first.
Alzheimer's disease vs delirium superimposed on it — dementia progresses over months, so a change over hours or days in someone with dementia is delirium until a physical cause has been excluded.
Anterograde vs retrograde memory loss — anterograde loss of new learning is the earliest deficit, while retrograde loss follows a temporal gradient in which the oldest memories survive longest.
Delusions vs hallucinations in Alzheimer's disease — delusions are the more common of the two and are most often persecutory, classically that belongings have been stolen; hallucinations are less common and predominantly visual.

Watch for

⚠️ Treating a sudden deterioration over hours or days as the dementia progressing. Alzheimer's disease moves over months and years, so an abrupt change means delirium until pain, constipation, urinary infection, dehydration or a newly started drug has been excluded.
Reaching for an antipsychotic as the first response to agitation. NICE NG97 puts the search for a physical or environmental trigger and psychosocial intervention first, and reserves antipsychotics for severe distress or immediate risk of harm, at the lowest dose for the shortest time.
Forgetting the antipsychotic risk in dementia with Lewy bodies. Where visual hallucinations are early, recurrent and well formed with fluctuating attention and parkinsonism, an antipsychotic can provoke a severe sensitivity reaction.
Assuming depression in dementia should be treated like depression elsewhere. NICE NG97 advises against routinely offering antidepressants for mild-to-moderate depression in dementia.
Reading a Mini-Mental State Examination score as the whole assessment. NICE is explicit that a cognitive score alone must not determine access to treatment, and function is the better staging guide.
Expecting the four cortical signs at first presentation. Aphasia, apraxia and agnosia cluster in the moderate stage; a mild-stage vignette that already has all of them should make you reconsider the diagnosis.

Use it again

Stage the person before answering anything else, using what they can still do rather than a test score, because most options in these questions are stage-specific.
Check the direction of memory lossnew learning failing while remote memory is preserved supports Alzheimer's disease, and the reverse pattern should make you look for another explanation.
Read the timescale of any deterioration described. Hours to days means delirium, months to years means the dementia, and this single check answers a large share of the management questions asked here.
When hallucinations appear, ask when they started and what came with them, since early well-formed visual hallucinations with fluctuation and parkinsonism redirect you to dementia with Lewy bodies and change the safety of any antipsychotic.
Before choosing any drug for behaviour, run the physical checklist — pain, constipation, infection, dehydration, sensory impairment, new medication, environment — because the guideline order is triggers first, then psychosocial measures, then medication.

In detail

Hook — why she can describe 1962 and not this morning

A daughter tells you her mother repeats the same question every ten minutes, yet gives a word-perfect account of her wedding day sixty years ago, and she cannot understand how both can be true of the same brain. It is the single most useful observation in this whole topic. Alzheimer's disease does not thin memory out evenly; it removes it in an order, and the order is from the most recently written backwards. Hold on to that direction of travel and the stages, the symptoms and most of the exam's favourite traps fall into place behind it.

Plain definition — a diary erased from the last page backwards

Alzheimer's disease is a slowly progressive degenerative brain disease whose defining early failure is in episodic memory (your record of the events of your own life, tied to a time and a place). Picture that record as a diary. What the disease erases first is the last page written, then the page before it, and so on backwards through the volume. So a new event never gets stored (this is anterograde amnesia, the inability to lay down new memories), while pages written decades ago survive for years. Onset is insidious (so gradual that no family can name the week it began) and the course is one of continuous decline over years rather than the step-by-step drops of vascular dementia.

The critical caveat — memory is not the whole illness, and often not the presenting problem

The commonest error on this topic is to treat Alzheimer's disease as a memory disease with some behaviour attached. In practice the behavioural and psychological symptoms of dementia — usually shortened to BPSD, meaning everything that is not a cognitive test result: apathy, depression, , , agitation, aggression, wandering, disinhibition and disturbed sleep — affect the great majority of people at some point in the illness.

They matter more than that description suggests. They cause more carer distress than the memory loss does, they are the commonest reason a family stops coping at home, and they drive admission to hospital and to care homes. A candidate who can stage cognition and cannot name what happens to behaviour has learned half the condition.

First principles — why the order of loss is the order it is

Work out what a memory has to survive to last. A new memory is laid down through the and the surrounding medial ; over years it is consolidated into the wider cortex, so an old memory no longer depends on the structure that formed it. Alzheimer's pathology reaches the medial temporal lobe early and spreads outwards through the association cortex afterwards.

Put those two facts together and the whole clinical order follows. The first thing to fail is the making of new memories, because the structure that does that job is hit first. Memories consolidated long ago sit elsewhere and survive, which is why the wedding in 1962 is intact while this morning has gone — a backwards gradient with the oldest memories most resistant.

Then the spread outwards predicts what arrives next. As the disease reaches the language cortex, word-finding fails; as it reaches parietal cortex, learned actions and recognition fail. The condition does not acquire new symptoms at random; it acquires whatever the next region of cortex was responsible for.

Structured walk-through — three stages, and the pace between them

In the mild stage the person forgets recent conversations and appointments, repeats questions, mislays objects and loses the thread of complex tasks, while personality, social manner and old memories look preserved. is often partly retained, which is one reason low mood is common here.

In the moderate stage the cortical signs arrive together: aphasia (loss of language, beginning with word-finding), apraxia (inability to carry out a learned movement such as dressing, despite normal strength) and (failure to recognise things or people through an intact sense). Help is now needed with washing and dressing, and most of the behavioural symptoms cluster in this stage.

In the severe stage speech reduces to a few words or none, walking and continence fail, swallowing becomes unsafe, and the person becomes fully dependent. Death usually follows a complication rather than the dementia itself, most often bronchopneumonia after aspiration.

For example, put a number on the pace. A man diagnosed with an initial score of 22 out of 30, declining at the roughly two-to-four points a year often quoted for untreated disease, a figure drawn from moderate-stage series, would pass 19, then 16, then 13, reaching about 10 in four years — carrying him from the mild band down to the floor of the moderate one. Use that to feel the tempo, not to make decisions: NICE NG97 is explicit that a cognitive score alone must not decide who is treated.

Look-alikes & differentials — the four that get swapped for it

Looks like Alzheimer's disease	The one feature that separates it
Dementia with Lewy bodies	Early, recurrent, well-formed visual with fluctuating attention and spontaneous parkinsonism, plus severe antipsychotic
Vascular dementia	Stepwise decline with focal neurological signs and vascular risk factors, rather than a smooth downward slope
Huntington's disease	Autosomal dominant, chorea, onset in mid-adult life, with executive and psychiatric change dominating over early amnesia
Depression (formerly called pseudodementia)	Prominent complaints of poor memory with "don't know" answers, a shorter and datable history, and low mood preceding the cognitive change

Diagnosis — how the illness and its stage are actually established

Diagnosis is clinical and rests on a history from someone who knows the person, a cognitive assessment, a physical examination and blood tests to exclude reversible contributors such as thyroid disease and vitamin B12 deficiency, with structural imaging to exclude other causes and to look for the medial atrophy that supports the diagnosis. Staging uses the pattern of daily function first and a cognitive score second: the bands conventionally taught are 21 to 26 for mild, 10 to 20 for moderate and below 10 for severe. Behavioural symptoms deserve their own assessment rather than being folded into the cognitive one, because a sudden worsening of behaviour is far more often delirium from pain, constipation, urinary infection or a new drug than a step down in the dementia.

Management — treat the trigger before you treat the behaviour, and NICE NG97 says so

NICE NG97 sets out the framework. For cognition, the cholinesterase inhibitors donepezil, galantamine and rivastigmine are the first-line drug treatment in mild-to-moderate Alzheimer's disease, and memantine is used in moderate disease where those are unsuitable, and in severe disease.

For behavioural and psychological symptoms the order matters more than the drug. Look first for a physical cause, unmet need or environmental trigger, then offer psychosocial and activity-based interventions tailored to the person. Antipsychotics are reserved for severe distress or an immediate risk of harm, at the lowest dose for the shortest period with regular review, because they raise the risk of stroke and of death in dementia; risperidone is the one antipsychotic licensed in the UK for short-term persistent aggression in moderate-to-severe Alzheimer's disease. Two further NICE positions are commonly tested: do not offer antidepressants routinely for mild-to-moderate depression in dementia, and be extremely cautious with antipsychotics whenever dementia with Lewy bodies is possible.

Exam pearl — which stage, and which symptom belongs to it

The high-yield habit is to place every symptom in the stage where it belongs. Early: forgetting new information with old memories intact, plus low mood while survives. Middle: aphasia, apraxia and together, with of theft, misidentification of relatives, failure to recognise one's own reflection and wandering. Late: , immobility, incontinence and unsafe swallowing. Before you move on, test yourself on the one that catches people out: a man with dementia who becomes suddenly and dramatically worse over two days — what should you look for before you call it progression?

In one line — an order, not just a decline

Take away one thing: Alzheimer's disease erases memory from the newest backwards, then adds aphasia, apraxia and as the pathology spreads outwards, with behavioural and psychological symptoms clustering in the middle stage and driving most of the carer distress — so stage the person by what they can still do, and always look for a physical trigger before treating a sudden change in behaviour.