Before I started medical school I volunteered at a nursing home full of elderly people with dementia. It was honestly heart-breaking. I would go in and introduce myself to the same people every Saturday. There was this one lady who would always tell me about the buttons on her cardigan and how she didn’t like her eyes and I would tell her that her eyes were lovely. She got excited when the tea trolley came around, loved sweets and got very agitated the time I tried to explain to her that her mummy was not around anymore. It was extremely saddening, and you just wanted to hug her, but you couldn’t touch her because she would get sexually aroused.
Definition: a syndrome encompassing progressive deficits in several cognitive domains.
Suggested that environmental and genetic factors play a role.
Majority of cases are idiopathic with rare monogenic cases.
Accumulation of β-amyloid peptide (β-42 peptides), a degradation product of amyloid precursor protein, results in progressive neuronal damage, neurofibrillary tangles, increased numbers of amyloid plaques and loss of acetylcholine. Defective clearance of β-amyloid plaques by macrophages appears to relate to altered macrophage gene expression.
Neuronal loss is selective- the hippocampus, amygdala, temporal neocortex, and subcortical nuclei are most vulnerable.
95% of patients also show evidence of vascular dementia.
Risk factors: family history; Down’s syndrome; genetic: homozygosity for ApoE e4 allele, PICALM, CL1 & CLU mutations; vascular risk factors; low physical/ cognitive activity; depression; loneliness; evidence on alcohol inconsistent.
-Vascular dementia: represents the cumulative effects of many small strokes
Vascular risk factors: hypertension, diabetes, hyperlipidaemia, smoking, AF, homocysteinaemia etc.
Evidence of vascular pathology: hypertension, past strokes, focal CNS signs
-Lewy body dementia: histology is characterised by Lewy bodies in the brainstem and neocortex. Lewy bodies are eosinophilic intracytoplasmic neuronal inclusion bodies, that are also present in Parkinson’s disease.
-Fronto-temporal (Pick’s) dementia: frontal and temporal atrophy without Alzheimer histology
-Genes on chromosome 9 are important
(Pick’s dementia is now a term reserved for fronto-temporal dementia with Pick inclusion bodies.)
-Other ameliorable causes:
-B12/folate, Thiamine deficiency (alcohol), Pellagra (Niacin- Vit B3- deficiency)
-CNS cysticercosis (tapeworm), HIV + cryptococcosis (fungus)
-Normal Pressure Hydrocephalus (dilated ventricles without enlarged cerebral sulci →gait apraxia, incontinence, dementia)
-Whipple’s disease (bacterium Tropheryma whipple)
Other less ameliorable causes:
-Repeated head trauma
-CJD (Creutzfeldt–Jakob disease- Mad Cow Disease)
-Familial autosomal dominant Alzheimer’s
-CADASIL (Cerebral Autosomal-Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy)
Epidemiology: common as people get older
Rare if < 55 years old, 5-10% if > 65 yrs
20% if > 80 yrs, 70% if > 100 yrs
-Alzheimer’s disease = commonest cause, 60-80% of all dementias
onset may be from 40 years, but before 60 years is exceptional
-Vascular dementia = ~ 25% of all dementias
-Lewy body dementia = 15-25%, 3rd commonest cause
Important to get a good history from both the patient and someone who knows them well.
-initial presentation is usually of memory loss over months or years
-may affect their activities of daily living
-ability to cope with financial affairs
-ability to deal with medications
-later stages- non-cognitive symptoms:
-agitation, aggression, mood disturbance (depression common)
–slow repetitious speech, logorrhoea (talking loads), flight of ideas
Also known as- Behavioural and psychological symptoms of dementia (BPSD)
–Alzheimer’s disease: enduring, progressive, global cognitive impairment; cognitive impairment is progressive but non-cognitive symptoms may come and go over months
visuo-spatial (gets lost), memory, verbal abilities, and executive function are all affected. Language is typically spared until late.
anosognosia- “lack of insight”- impaired ability to understand and perceive their illness
Initially: anterograde amnesia, personality change, apathy, loss of concentration, disorientation
Later: all cognitive domains affected
irritability, mood disturbance (depression or euphoria), behavioural change (e.g. aggression, wandering, disinhibition), psychosis (hallucinations or delusions), agnosia (may not recognise self in mirror)
incontinence, loss of independence
myoclonus, seizures may occur
Towards end: often become sedentary, taking little interest in anything
-Vascular dementia: characterised by sudden onset and stepwise deterioration
-Lewy body dementia: typically with fluctuating cognitive impairment, detailed visual hallucinations and later, parkinsonism
-Fronto-temporal dementia: early preservation of episodic memory & spatial orientation
-behavioural/ personality change
-hyperorality (putting random things into their mouth)
Cognitive testing: use validated dementia screen (e.g. AMTS, MMSE, MOCA, ACE-III)
Mental state examination: may reveal anxiety, depression or hallucinations
-Vascular dementia: hypertension, focal CNS signs
-Lewy body dementia: Parkinsonism later on = tremor, rigidity, bradykinesia
Investigations are aimed at excluding treatable causes of dementia.
-Bloods: FBC, ESR, U&Es, Ca2+, LFTs, TSH, autoantibodies, B12/folate, syphilis serology, consider HIV serology
–CT/MRI- for vascular damage, haemorrhage or structural pathology
-exclude tumour, infarction, inflammatory causes, subdural haematoma
-may show cerebral or hippocampal atrophy in Alzheimer’s
Consider: EEG (exclude non-convulsive status epilepticus as cause)
Lumbar puncture (exclude encephalitis, prion disease)- Tau and β-42 peptide levels can also be measured.
Functional nuclear imaging (FDG, PET, SPECT)-mainly for research e.g. showing amyloid distribution and perfusion of brain
If indicated: metabolic, genetic
Patients will become increasingly dependent and develop increasingly complex needs.
-Care coordinator to coordinate teams and services e.g.:
-occupational therapist, district nurses, community psychiatric nurses
-respite care in hospital
-day care/ lunch clubs
-Consider whether the patient has mental capacity and suggest the making of advanced directive or appointing a Lasting Power of Attorney for the future
-Develop routines to help maintain independence for longer
-Plan ahead: relocation, care home, family involvement, carers
-Day services: multisensory simulation, massage, music, animal therapy, aromatherapy, structured conversation and exercise – stimulate patients and allow carers a break
-Support carers- respite care, carers’ groups, telephone helplines
⇒ Challenging behaviour-
-rule out infection and pain as cause
-consider TRAZODONE (50-300mg at night) or LORAZEPAM (0.5-1mg/12-24h PO), if non-pharmacological therapies fail.
-Severe agitation- get help
–antipsychotics can help improve positive symptoms but may worsen cognition, verbal fluency, and longevity
-e.g. quetiapine, risperidone, olanzapine
haloperidol can be useful in short-term
–Avoid anti-psychotics in Lewy body dementia due to increased S/E risk.
-Some evidence for anticholinesterases helping
⇒Depression- try an SSR e.g. CITALOPRAM (10-20mg OD)
If severe- MIRTAZAPINE (15-45mg at night, if eGFR > 40)
Cognitive Behavioural Therapy (CBT) can help
⇒Avoid drugs that impair cognition e.g. neuroleptics, sedatives, tricyclics
-refer to specialist memory service
–anticholinesterase inhibitors are modestly effective in treating Alzheimer’s
e.g. DONEPEZIL, RIVASTIGMINE (may also improve behavioural symptoms in Lewy Body dementia), GALANTAMINE
-blood pressure control
–Ginkgo biloba (antioxidant) may improve wellbeing
-Huperzine A (Chinese medicine) may help
–Prevention: polyunsaturated fatty acids, folic acid and B vitamins may have a role
-poor quality of life
-loss of independence
-devastating effect on family
Depends on cause. In Alzheimer’s, the mean survival from onset of unequivocal symptoms is 7 years.