Alzheimer’s Disease

Alzheimer’s disease (AD)

Most common form of dementia in the elderly – risk doubles every 10 years after age of 65. Relentless neurodegenerative disorder which is characterised by progressive multiple cognitive deficits (memory loss, impaired thinking, visuospatial impairment), disorientation, language dysfunction, changes in personality, mood changes and an inability to carry out basic daily tasks.
Affects 4% of those >85yrs

Pathophysiological findings are loss and atrophy of neurons in several areas of the brain, enlargement of ventricular system, reduced synapse density, accumulation of amyloid, senile neuritic plaques and neurofibrillary tangles. The cognitive changes appear to be due to decreased cholinergic neurotransmission.

Widely assumed to result from an increase in the production or accumulation of beta-amyloid protein  nerve cell death. The damage to neurons may be mediated by inflammation and oxidative damage. Insulin resistance may be a factor. Defects have been found on chromosomes 1, 14, 19, 21 – a susceptibility locus on chromosome 12 exists. The apoE4 variant brings the age of onset sooner. Hypertension may increase risk.

Clinical features:
Diagnosis is difficult in early stages – typically insidious onset of dementia and the exclusion of other diseases. Subtle early signs of memory loss may be put down to ‘benign senile forgetfulness’. Definitive diagnosis can only be made by biopsy or at autopsy.
Early features:
• Loss of recent memory – forgetfulness of recent events or information; long term memory may be heightened at first; confusion; diminished judgement (eg driving, finance’s); diminished abstract thinking, decision making, problem solving and ability to follow instructions; mood swings; personality changes; disorientation to time
Later features:
• Difficulty feeding and bathing; suspiciousness; anxiety; easily agitated; wandering behaviour; difficulty recognising family; purposeless motor action; apathy; delusions; Established more severe symptoms  loss of speech; weight loss; loss of control of bladder and bowel; total dependence on a caregiver; dysmobility and its associated problems; motor features (rigidity, bradykinesia, parkinsonism gait)
Terminal stages:
• Limited vocabulary (<6 words); unable to walk or sit without assistance; difficulty eating; weight loss; decreased consciousness; urinary incontinence; recurrent infections

Stage 1 – some evidence of memory and cognitive impairment; appears somewhat normal with eccentric behaviours; some personality changes; judgement is affected
Stage 2 – more obvious signs of memory and cognitive impairment; significant personalty changes; no physical changes, but do wander and can get lost
Stage 3 – have signs of physical changes; urinary incontinence; tend to be confined to a chair or bed.

Clinical course usually tends to be predictable. Reisberg et al (1994) developed the Global Deterioration Scale to describe the clinical course:
Stage 1 – no symptoms
Stage 2 – subjective forgetfulness with normal findings on examination of mental state
Stage 3 – Difficulty functioning at work and home, detectable by family; memory deficits detectable by examination
Stage 4 – decreased ability remembering current events, travelling or handling complex finances
Stage 5 – Disorientation to time and place; need for assistance in choosing clothes
Stage 6 – Disorientation to people; need for supervision in dressing, eating, toileting
Stage 7 – Severe speech loss; incontinence; motor rigidity

Rule out treatable causes.
General measures – adequate nutrition and sleep; adoption of a daily routine; clocks and calendars for day and time orientation;
Appropriately structured social and physical activities.
Consideration given to financial responsibility of the patient, the ability to drive and ability to carry out other potentially dangerous activities.
Caregiver and family education (support organisations)
Management of co-morbidities
Provision of safe environment (eg locks on doors; grab bars by bath)

Management of behaviour disturbances – eliminate provoking factors; behaviour modification techniques; pharmacological intervention; ensure patient and caregiver safety. The key to behavioural management is changing what the patient experiences. The caregiver can use techniques such as redirection and distraction. Environmental cues that act as stimuli should be removed or avoided where possible.

Cholinesterase inhibitor (based on ‘cholinergic hypothesis’ of decreased cholinergic neurotransmission):
• loss of neurons in basal forebrain nuclei  decreased production of choline acetyltransferase  decreased ability to synthesis acetylcholine  cholinergic deficiency. Cholinesterase inhibits action of acetylcholinesterase  action of available acetylcholine is increased
• shown to have moderate beneficial effects on neuropsychologic, behavioural and activities of daily living in mild to moderate cases, but clinical significance of these changes are still not clear
• up to a third develop 5-15% cognitive improvement compared to placebo
• eg tacrine, donepezil, rivastigmine, galantamine

• may help ameliorate the oxidate mediated accumulation of beta-amyloid protein
• Vitamin E and selegiline has both been shown to moderately slow progress

Psychotropic agents:
• for agitation, psychoses, depression and insomnia
• some concern about overuse for ‘chemical restraint’ reasons

Average survival from diagnosis is about 7 years.

Advice to the caregiver and family :
1. Be realistic about the nature of the illness and plan accordingly
2. Recognise your personal need for help and respite. Seek respite, accept it, and pay for it if necessary
3. Seek a support group, usually through the Alzheimer’s Association, for specific advice and psychological support
4. Make communication within the family optimal so that the caregiving burden is shared among family members
5. Ensure optimal caregiver health – enough sleep, exercise, and social contacts
6. Remember that there will be life after the patient is gone
7. Become informed about the illness to anticipate problems and to plan strategies
8. Plan financial and legal aspects early, including the will, placement, and intensity of treatment issues
9. Be aware of the most positive and important work of the caregiver: to continually find and optimise the preserved function of the patient. This is not only reduces the burden but increases the quality of life of the patient and the caregiver and increases the quality of their relationship to each other

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