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 5 -10 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 Aβ peptide rather than a soluble fragment.

Aβ 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 Aβ

Q3  Provide a classification of dementia.

Classification for dementia:

Alzheimer Disease (60 - 70%)

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?

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?

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 ASSESSMENTMMSE- limited by culture and education

SCREENING FOR DEPRESSIONTo 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?

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?

• http://www.archi.net.au/resources/safety/clinical/reliable_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 2005. A total of 186 new patients were seen in 2005 for cognitive assessment.

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