Dementia

Dementia

·        = Chronic, generalised impairment of memory (key feature), intellect, and personality with no impairment of consciousness (cf delirium)

·        Acquired

·        Not a feature of normal ageing

·        Diagnostic criteria:

o  Development of multiple cognitive deficits including both:

§  Memory impairment (either ability to learn or recall), and 

§  One of aphasia (language disturbance), apraxia (impaired motor co-ordination), agnosia (impaired recognition despite intact sensory function), disturbance in executive functions/personality/social conduct 

o  Not due to general medication condition, substance use, or delirium

o  Significant impairment in social or occupational functioning, and a decline on previous function

·        Epidemiology: 5% of 65 – 80 year olds, 20% of those over 80

·        Assessment:

o  General: age, absence of psychiatric history or co-existing physical illness 

o  General account from carer, including memory impairment, behaviour change, mood change, physical symptoms, disruption of ADLs 

o  Onset: insidious or acute

o  Stepwise deterioration (suggests vascular), seizures

o  Fluctuation, including early evening, nocturnal worsening (“sunsetting”)

o  Family history including Huntington‟s

·        Clinical Course:

o  Amnesia: 

§  Early: forget names, appointments, repetitive in conversation, some insight, leaving elements or taps on

§  Later: forget faces, recent events

§  Advanced: forget past, identity, relatives, no insight

o  Language:

§  Early: difficulty word finding 

§  Later: ¯articulateness, difficulty following conversation

§  Advanced: rambling, incoherent 

o  Dyspraxia (difficulty sequencing tasks): Difficulties with dressing, cooking ® safety issues: wandering, kitchen/road safety

·        Other: depression (difficult to distinguish), psychosis, personality & behavioural change

·        Examination: 

o   General: posture, gait, consciousness level, wandering, restlessness, feeding and dressing difficulties

o   Mental Status examination 

o   Neuro: focal signs, involuntary movements, pseudobulbar signs (swallowing, speech production), primitive reflexes 

·        Investigation: 

o   Cognitive Function: test with mini-mental state: 26 or above = normal, 20 – 26 = mild, 11 – 20 = moderate, < 10 = severe

o   FBC (macrocytosis) and LFTs: is it alcohol induced?

o   Exclude: thyroid, space occupying lesion, B12 deficiency, AIDS, syphilis 

o   CT if focal neurological signs, new or odd psychiatric disorder, or age < 75 with shorter history. NB include temporal lobe orientated views, as atrophy of medial temporal lobe is one of the earliest CT findings in Alzheimer‟s disease 

·        Treatment:

o   Treatment of any cause found.  Treatable causes include:

§  Benign brain tumour, especially subfrontal meningioma

§  Subdural haematoma

§  Wilson‟s disease: akinetic rigid syndrome, bulbar palsy

§  Deficiency: B12, B6, B1

§  Hypothyroidism

§  Alcoholic dementia

§  Infection: HIV, syphilis 

o   Improve functional ability, relieve distressing symptoms (eg secondary incontinence), regular routines (diaries, reminders), establish enduring power of attorney early on (using PPPR act later on is more involved), practical assistance (eg meals on wheels, rest home care), support for the family (involvement in rehabilitations, information, etc)

o   Drugs:

§  Cholinesterase inhibitors:

·        Hold off progression for a year or two?  Better motivation, improvement in ADLs

·        12 weeks before effect can be reliably assessed

·        Side effects: nausea, diarrhoea, vomiting, muscle cramps, fatigue, anorexia 

·        Eg Rivastigmine (Exalon): titrate up monthly: 1.5 mg bd ® 3.0 mg bd ® 4.5 mg bd ® bd 6.0 mg 

·        Eg Donepezil (Aricept): 5mg od ® 10 mg od after a month if necessary

·        Cautions: peptic ulcer disease, arrhythmias

·        Not currently funded and pretty expensive

§  Other drugs with possible benefit:

·        Antioxidants (eg vitamin E)

·        NSAIDs

·        Oestrogen

o   Treatment for vascular dementia: control of blood pressure and aspirin

Aetiology

·        Alzheimer‟s: 

o   50%. F > M.  Course 6 – 8 years (Þ may die of something else first)

o   If < 65 then Alzheimer‟s disease, if > 65 then Senile dementia, Alzheimer‟s type

o   Clinical diagnosis.  Diagnosis only certain at autopsy

o   Presentation: 

§  Marked impairment of memory: anteriograde and retrograde (eg how old are you, are you married, what are your children‟s names, etc)

§  Aphasia with word finding defect early on

§  Visuo-spatial problems: getting lost

§  Loss of interest: hobbies, dealing with finances, new circumstances, etc 

o   Gross pathology: Atrophy in frontal, parietal, occipital and temporal regions, with secondary widening of sulci and dilation of ventricles

o   Micro: 

§  Neurofibrillary tangles: intracytoplasmic bundles of filaments that displace the neuron‟s nucleus. Contain abnormal form of the protein tau

§  Senile plaques: extracellular intracortical spherical clusters of dilated axons and dendrites surrounding a spherical deposit of amyloid fibrils (amyloid beta peptide). Motor and sensory cortex sparing. A few are normal. There are lots in Alzheimer‟s 

§  Amyloid angiopathy

§  Granulovacuolar degeneration: clear intraneuronal cytoplasmic vacuoles

o  Pathogenesis:

§  ?Accumulation of amyloid beta protein, with failure to exocytose the protein 

§  Apoe4 allele is a marker for Alzheimer‟s but is not yet recognised as a screening or diagnostic tool

·        Vascular:

o  20%.  Previous history of CHD, stroke, high BP, etc.  M > F 

o  Caused by discrete infarcts (ie multi-infarct dementia) but also small vessel disease (eg cerebral arteriolar sclerosis from chronic hypertension)

o  Presentation: Often impaired attention and frontal features, emotional lability 

o  Multiple subcortical white matter injury ® Binswanger disease (damage to association fibres)

·        Defuse Lewy Body Dementia: 20%: 

o  Often associated Parkinsonian features (rigidity, tremor and bradykinesia) – less tremour but trunkal rigidity 

o  Can have fluctuating attention and visual hallucinations (so like delirium) 

o  Very sensitive to anti-psychotics.  A small dose can ® profound tranquilliser effect

·        Pick‟s Disease: Much less common, but similarities with Alzheimer‟s. Differences are early onset of personality, behavioural changes and language impairment. Atrophy of frontal and temporal lobes (ie clearly localised). Microscopically, surviving neurons show ballooning degeneration (Pick‟s cells) and Pick‟s bodies (filamentous intracytoplasmic inclusions). No senile plaques or neurofibrillary tangles

·        Alcoholic Dementia.  See Topic: Pathological Effects of Alcohol on the Brain

·        Rarer causes:

o  Creutzfeldt-Jakob Disease (CJD) 

§  Fatal, rapidly progressive dementia with psychiatric and behavioural disturbances. Less than 1 per million per year, usually elderly

§  No helpful lab findings (including CSF) 

§  Aetiology: abnormal neuronal protein coded by the PRNP gene. Prion causes conformational change from a a-helix to a b-pleated sheet ® chain reaction ® neuronal death

§  Can be transferred via pituitary extracts, dural grafts, etc

§  15% of cases familial 

§  No macroscopic changes. Microscopically: spongiform encephalopathy – vacuoles in neurons and neuropil (ie extracellular) ® neuronal loss and gliosis (marked astrocytosis) 

o  Variant CJD (vCJD). Affected young adults, progressed more slowly, early behavioural changes. Spongiform changes plus plaques composed of prion protein. Caught from Bovine Spongiform Encephalopathy (BSE, Mad Cow Disease). Prions very difficult to inactivate (eg standard disinfectants, formalin, UV light don‟t work)

o  Huntington‟s Disease:

§  Prevalence: 7 per 100,000 

§  Clinical: Choreoathetotic movements and progressive dementia from age 35 – 40. Depression, erratic behaviour, apathy, problems with speech and swallowing. Death in 15 years on average 

§  Genetics: Autosomal dominant, short arm of chromosome 4 

§  Gross: diffuse gyral atrophy, marked atrophy of caudate nucleus and putamen, dilation of ventricles

§  Micro: loss of neurones in atrophied areas, replaced by fibrillary gliosis

o  HIV & syphilis