This leading cause of dementia is the big neuropsychiatric disorder of our times, dominating not just psychogeriatric wards, but the lives of countless children and spouses who have given up work, friends

Alzheimer's disease (AD)

 This leading cause of dementia is the big neuropsychiatric disorder of our times, dominating not just psychogeriatric wards, but the lives of countless children and spouses who have given up work, friends, and all accustomed ways of life to support relatives through the last long years. Their lives can be tormented `l am chained to a corpse' (p329) or transformed, depending on how gently patients exit into their 'worlds of preoccupied emptiness'.% Mean survival: 7yrs from onset. Suspect Alzheimer's in adults with enduring,' acquired deficits of visual-spatial skill ('he gets lost easily), memory, and cogni-tion, eg tested by mental test scores + other neuropsychometric tests (p59). Onset may be from 40yrs (earlier, in Down's syndrome, so notions of 'senile' and 'pre-senile' dementia are blurred, and irrelevant). Cause: Accumulation 13-amyloid peptide, a degradation product of amyloid precursor protein, result-ing in progressive neuronal damage, neurofibrillary tangles, t numbers of senile plaques, and toss of tne neurotransmitter acetytcnotine trom damage to an ascending forebrain projection (nucleus basalis of Meynert; connects with cortex). AD shares some pathological processes with vascular dementias! Memory loss is not like loss of land with a rising tide: the last memories to be sunk in the sea of forgetfulness are not earliest or latest, but the deepest, the most personal, and the most bizarre: prime ministers come and go, but, for dementing British patients of a certain age, the last name retained is that of Mrs Thatcher. When this name sinks into oblivion (fame's eternal dump-ing ground'), often long after that of sovereigns, deities, spouses, and children, one may safely say that the waters have covered the sea. Risk factors Defective genes on chromosomes 1, 14, 19, 21; the apoE4 vari-ant brings forward age of onset. Insulin resistance (p295) may be important! t-Diagnosis is often haphazard, as the exact form of dementia used not to influence outcome, provided B12 and TSH were normal. This view is hard to justify now that specific treatments are available for Alzheimer's. Specialist input with imaging is the ideal (this helps rule out fronto-temporal demen-tias, Lewy body, vascular dementias, and Pick's disease). Presentation Memory/cognition 1; behavioural change (eg aggression, wan-dering, disinhibition); hallucinations; delusions; apathy; depression; irritability; euphoria. There is no standard natural history. Cognitive impairment is pro-gressive, but behavioural/psychotic symptoms may go after a few months or years. Towards the end, often but by no means invariably, patients become sedentary, taking little interest in anything. Parkinsonism (p382), wasting, mutism, incontinence ± seizures may occur. Theoretical issues Potential strategies (*indicates randomized trial evidence) • Prevent breakdown of acetylcholine,* eg anticholinesterases, etc. (see BOX). • Prevent overstimulation of NMDA receptors by glutamate; memantine (see BOX) is an NMDA antagonist. (NMDA = N-methyl-D-aspartate, p335.) • Stimulating nicotinic receptors may be protective (smoking is not a solution!).F5 • Preventing neurotoxicity from homocysteine by ensuring good B12 intake (p374). • NSAIDs to 1 production of 13-amyloid. NB: NSAIDs don't stop progression of AD.*2 • Some anti-oxidants may be protective, eg ginkgo biloba or vit C with D.,71 • 1Arteriopathy (AD risk rises with BPt) and normalize pulse pressure (PP = 70-84): if PP > 84mmHg (reflects arterial stiffness) risk of AD is t; if PP < 70 (reflects poor perfusion) risk of AD is also raised.% Statins* (p707) may prevent ADF9i eg by 1 brain cholesterol synthesis (.-. less amyloid plaque formation). • Cognitively stimulating hobbies may help: a 1-point rise in cognitive activit score can 1 risk of AD by 33%.N NB: HRT (OHCS p18) was thought turotect,82 but the WHIMS* trial found t risk of AD (2% vs 1% on placebo)