Case 3 – old timer’s disease

Trigger – PC Elllie, aged 80, has been your patient for 5 years. Today she complains of poor memory and says she “seems to have lost the keys to her front door” She wonders if she may have “old timer’s disease”.

Q1 What are the chances that Ellie is suffering from Alzheimer disease? Most common form of dementia, 65% of any age group. RF for Alzheimer disease:-Genetics (some familial inheritance) Main features: - onset late 50s – 60s - insidious onset - early loss of short-term memory - progressive decline in intellect - more common in Down syndrome - death in years CF: progressive memory loss, decline in language (aphasias, agnosia), apraxia, loss of executive func., behavioural change, loss of insight, depression. Ellie could have Alzheimer disease, however with her insight and everything else appearing normal, she could just be having memory issues. Could be suffering from depression…

Q2 What is the pathophysiological mechanism that underlies this presentation? Pathophysiology of Alzheimer: Pg 1316 of Robbins

β secretase cleaves the APP (unknown func) instead of α secretase (both occur prior to γ ), resulting in an A β peptide rather than a soluble fragment. A β are highly prone to aggregation: small (directly toxic  neuronal dysfunction)  large  fibrils Neurotoxic-ness  change membrane properties and cause synaptic dysfunction. Aggregates are hard to remove (centre of plaques)  inflammatory response from microglia and astrocytes. Could remove the aggregate, but also causes mediator secretion  damage. Also get tangles in axons due to ‘tau protien’ which fails to bind to microtubules as per normal, increasing damage. All leads to cerebral atrophy. Hippocampus and amygdala involved early. APP gene held in chromosome 21 (why does this matter?). Point mutations and Downs. Also presenilins (PS1 and 2)  gain of function, being γ ↑ production of A β

Q3 Provide a classification of dementia. Classification for dementia: Alzheimer Disease ( %) Dementia with Lewy Bodies (15-30%) – cognitive impairment, parkinsonism, hallucinations, psychosis, alertness fluctuation Vascular Dementia – isolated symptoms related to where the infarct has occurred Frontotemporal dementias – personality change, hyperorality, cognitive ecline (esp language and exec func) Advanced Parkinsons dementia Chronic Alcohol use – thiamine? HIV associated dementia What about normal ageing or ‘mild cognitive impairment’?

DSM IV criteria A1 – memory impairment A2 - ≥ 1 cognitive disturbance (aphasia, apraxia, agnosia, executive functioning) B – Disturbances significantly interfere with social and work functions C – Gradual onset and continuing cognitive decline D – Not due to a known organic cause (drugs, illness, CVA) E – Not a delirium F – Not due to another Axis 1 Disorder (eg depression)

Q4 Would you check whether Ellie is suffering from dementia or reassure her that many people have mild memory impairment with age, and this does not mean she is suffering from dementia? What is gained by diagnosis?

Yes I would assess her because……… Dementia is a complex condition. It develops slowly and early signs of dementia are very subtle. Delay in diagnosis has clinical and social implications for people with dementia and for their families. Earlier recognition that a problem exists may facilitate earlier access to resources, information, treatment and support Overseas and Australian studies have estimated the average time from first symptoms to diagnosis, as reported by informants, to be between 1 and 3 years,with symptoms recorded in GPs’ medical records as early as 5 years before diagnosis.

Q5 If you decide to test Ellie for dementia, what tests could you perform in the general practice setting? What factors may influence the results of these tests?

There is no simple test for the diagnosis of dementia. Diagnosis is made on clinical assessment and supported by investigation results. This includes a comprehensive assessment to ensure that other conditions that show similar symptoms are identified or eliminated, and differentiating which disease(s) is (are) causing the dementia.

COGNITIVE ASSESSMENT MMSE- limited by culture and education SCREENING FOR DEPRESSION To differentiate between dementia and depression (often co-exist) Geriatric Depression scale (GDs) REFER FOR OTHER INVESTIGATIONS- to rule in/out differentials (see next question)

Q6 If Ellie scores in the dementia range, what other conditions would you consider that may cause dementia?

LR Delirium Pseudodementia caused by severe depression drug induced effects (many drugs can cause cognitive impairment and look specifically for central effects of sedatives, hypnotics, analgesics and antipsychotics) vitamin B12 deficiency Hypothyroidism brain neoplasm subdural haematoma

MURTUGH- CAUSES The important causes of dementia are: degenerative cerebral diseases, including Alzheimer's disease (about 60%) dementia of frontal type (up to 10%) dementia with Lewy bodies (up to 10%) vascular (15%) alcohol excess (5%) AIDS dementia cerebral tumours Cruetzfeldt-Jakob disease Pick's disease neurosyphilis

What blood tests and other tests should be performed? Justify each answer MRI or CT - scanning of the brain is performed in most patients with dementia to look for infarctions, hemorrhage, mass lesions, hydrocephalus, demyelinating lesions or other structural abnormalities Lab testing performed on almost all includes serum chemistry: (electrolytes, blood urea nitrogen (BUN) and creatinine, serum calcium, magnesium) to rule out metabolic etiologies, complete blood count and ESR: screens for anemia, leukemia, vasculitis and infection, serum vitamin B12 level to screen for B12 deficiency, thyroid function studies to detect hypothyroidism, and liver function tests to exclude hepatic encephalopathy, and to seek evidence of chronic alcohol abuse

Nontreponemal serologic tests for syphilis: to rule out general paresis and syphilitic chronic meningitis Arterial blood gases: if anoxia-hypoxia, chronic hypercapnia is a possibilityUrine for heavy metals (24 hour collection) is occasionally performed when intoxication is suspected Urine drug screen is performed for patients with suspected substance abuse. Useful if intoxication with barbiturates, bromides, benzodiazepines, phenothiazines, haloperidol, lithium, certain combinations (thioridazine/lithium, haloperidol/methyldopa) Blood drug levels of certain drugs can be performed if toxicity is suspectedElectroencephalogram (EEG) is performed if seizures are suspected or if prion diseases are considered

Q8 What is the role of a specialist or memory clinic? e_memory_clinic The Specialist's one hour appointment was insufficient to accommodate the use of the cognitive assessment tool known as the Alzheimer's disease Assessment Scale - Cognition (ADAS-Cog). Involve a clinical nurse consultant then sees a specialist More than 50% growth in clinic activity between 2002 and A total of 186 new patients were seen in 2005 for cognitive assessment.

For the most part, dementia mx can be planned by GP When to refer: 1) Atypical presentation Showing symptoms or signs are not common for most typical cases of dementia When there are symptoms to suggest another important illness (normal pressure hydrocephalus, Creutzfeld-Jakob disease, dementia with Lewy bodies ) 2) Counselling family members when familial Alzheimer's disease is being considered Early onset of Alzheimer's disease runs in families A high risk for heritability may prompt the need to inform the rest of the family 3) Potentially reversible dementias Uncommon Has recognizable characteristics 4) Concern about co-existing depression in dementia and other behavioural and psychological symptoms 5) Treatment problems or failures Early experience with treatment demonstrates that the signs and symptoms do not get better Some symptoms improve while others worsen Failure to respond to anti-dementia treatment 6) Assessment of competence, including driving A specialist can determine whether the person you care for is able to make a decision when making a will, executing financial decisions or making decisions about future health care and living arrangements 7) The opportunity to enroll patients in research studies Referred to specialist memory clinics for enrollment in research studies Some evidence suggests that patients can benefit from participation in research studies

Q9 What other services would you consider for Ellie? Support groups – Alzheimer’s Australia Carer available? Adjust behaviour i.e. establish simple routines, break tasks in to smaller chunks etc. Encourage exercise ACAT assessment – will see be able to live alone if she does already Diet – meals on wheels Blue Care nurses – in later stages Financial support – govt pension? Decision – making capacity, legal considerations