Old Age Flashcards
What is the definition of dementia according to DSM?
‘loss of intellectual abilities of sufficicent severity to interfere with social or occupational functioning’
How long has the relationship between olda ge and memory been considered?
Ancient greeks and egyptians were aware that increased age is associated with memory disorders
Who is a case study for dementia?
Ronald Reagan - Mother died from AD. FAther = alcoholic. Childhood = alcoholism and financially struggling. actor –> president. STRESSFUL
What do we know about the gene apoE-4?
It is carried by 4-8% of people aand appears to determine the age at which some forms of late onset AD emerge
Who came up with Alzheimer’s Disease?
Alois Alzheimer (1907)
what is the prevalance of AD?
over 65s = 5-7%
Over 85s = 29%
What about diagnosis of AD?
Definitive diagnosis can only be done post-mortem - microscopic changes in brain tissue.
LAter starges diagnositc guidelines= 85%-90% accurate (1984)
How do AD patients act in a mental state exxam?
Circumstantial, repeat themselves and lack richeness of detail
What two microsopic signs are involved in AD?
Neurofibrillary tangles - and amyloid plaques
What are neurofibillary tanlges?
webs of abnormal filaments within a nerve cell
Filaments = made up of protein tau. If tau = misshaped or tangled = neuron tube colapses.
What did Sham & Morris, 2011 show?
Although abnormal tau aggression can occur indepenently, there is reason to beleive that build up of tau protein = accelerated by an increasing burden of amyloid in the brain
What are amyloid plaques?
Neurons in the brain secrete a sticky protein substance called beta amyloid. It is produced faster than it can be cleared away and broken down. Amyloid accumlates – makes amyloid plaques. These interfere with synaptic funcioning and set off a cascade of events –> death of brain cells
What di Jalburt et al, 2008 find?
Having apoE-E4 form of APOE gene = associated with the more rapid build up of amyloid in the brain
What is the caspase theory?
beta amyloid stimulates caspases (type of protease) whihc become enzymes that destroy neurons.
Primary disturbanec = in the acetylcholine (Ach) system - involved in learning and memory
AD people have insufficient choline acetyltransferase (enzyme that catalyses synthesis of Ach)
What dot he genes involvedin late onset familial AD lead to ?
Excess beta amyloid
Where is the apoE gene found?
chromosome 19 - 3 common forms = e3, e4. e2
What does the e4 allele do?
Production of E4 – damages neurone microtubules
What do apoE2 and apoE3 do?
Protect the tau protein – stabilises microtubules
What gene is inovoled in early onset familial AD?
Defective presenilin gene – involved in premature brain ageing
How many genes do research estimate account for genetic risk of AD
4 genes account for 1/2 the genetic risk of AD
Presinilin 1 & 2, AP and apoE
What did the Honolulu-ageing study involve?
longitudinal study on Japenese American males mid-late adulthood
Heavy smoking in mid life = increased risk of AD
Men who walked 2 miles a day = decreased risk of AD compared to those who walked 1/4 - 1 mile
What did the experiment involving older adults in sweden involve?
36% increase in risk of AD by age 79 for every unit increase of BMI age 70
Who did an experiment involving nuns and what did htey show?
Snowdon et al, 1998 – elderly nuns whosing signs of AD – decades earlier had written essays low in idea density and grammatical complexity
What two drugs? can be used to inhibit anticholinesterase and what does tha tenzyme do?
THA + DH
The enzyme destroys Ach after synaptic release
What effects can THA have?
Toxic effects in liver and the required does = too much for some
What effects can DT have?
Gastrointestinal effects but required dose = lower and no interference with liver function
What does clioquinol do?
antibiotic which breaks up chemical bonds holding amyloid together
What do anti-oxidants do?
When beta-amyloid breaks into fragments, free radicals form that damage neurons???
Quote on complexity of the brain?
Thompson (2000) – the brain is the most complex structure in the human universe
What can episodes of dperession cause?
Speck et al (1999) – can double risk of AD up to 20 years later
What is delirium
State of acute brain failure that lies between normal wakefulness and stupor or coma
What does delirum involve?
sudden onset, fluctuatitng state of awareness. Essentially unable to carry out purpose mental activity of any kind. elderly = particularly at risk
Who else are particularly at risk from delirium and why?
children = maybe because brains aren’t develope dfully yet
Other risk factors for delirium?
Dementia, depression, tobacco use (Fricchione et al, 2008)
Delirium criteria?
Disturbance of concousness, change in cognition (e.g. memory deficits), develops over short period of time.
Distrubance tends to be caused by the direct physiological consequences of a general medical condition
What horrible stat is there for elderly delirium and death?
Witlox et al, 2010 – 25% of elderly die within following 6 months
What’s dementia about?
No sudden onset, symptoms do not wax and wane. Gradual onset.
Memory = affected irst. Then, amrked deficicts in abstract think ing, acquiring of new knowledge, problem solving and judgement
Can be reversible if underlying cause = removed/trated (e.g. vitamin deficiency)
Hwo many differnet disorders have ben found to cause dementia ?
Bonde and LAnge (2001) – at least 50.
What are the most common neurogenerative disorders and according to who?
JAlbert et al, 2008 – AD then PD
Prevalence of PD?
65-69 = 0.5 -1 %. over 80 = 1 -3 %
What are the symptoms?
Motor - resting tremors or rigid movements. Underlying cause = loss of dopamine neurons in the substantia nigra.
How can symptoms be temporarily reuduced?
Miraplex medication - increases availblaility of dopamine in brain. Symptoms return wehen meds wear off
When are genetic factors and enviornmental facros mroe important?
Wirdefelt et al (2011) - genetic factors = more important in earlier development. Enviornmental = later development
What is huntingdon’s disease?
Rare degerneative disease of CNS. 1/10000 Mid life start (40 ish). Men and women = affected equally. Chronoic, progressive chorea (involumtary and irregular mvements that flow randoml from one area of body to another)
What is the relationship between cog problems and motro problesm re HD?
Shoulson and Young 2011 – cognitive problems due to the progressive loss of brain tissue that occurs as muh as a decade before the formal onset of the illlness
What happens to HD patients eventaully?
Dementia and death - normally 10/20 years after level of illness
Where is the dominant gene for Huntingdons?
Chromosome 4
Do people want to be tested for the dominant HD gene?
Shoolson & Young, 2011 – in US, about 10% of those eliggible for testing choose to be tested. HAyden (2000) – majority of those who ask to be tested = women
What is AD??
Progreessive and fatal degenerative disease. Inperceptible onset and usually slow but progressively deteriorating cause. Terminating in delirium and death.
When is diagnosis normally given for AD?
Post-mortem for sure
Normally only given out after all other potential causes of dementia = ruled out
When does AD normally begin?
About 45 – Malaspine et al, 2002
Horrible statistic re death after AD diagnosis?
Jalbert et al, 2008 – median time to death = 5.7 years after time of 1st clinical contact. Women = slightly higher risk at developing AD
AGe related risk statistic re AD?
Hendrie, 1998 – estimated that rate of AD doubles ever 5 years after a person reaches 40.
How many will be living with AD by 2030 ?
Vrengdenhil et al, 2011 – 66 million
Loneliness and AD?
Wilson et al, 2001 – 800 PPs. If lonely = twice the risk of developing AD over course of 4 years. May explain higher prevalence in women – outlive husbands.
What other other risk factors of AD
JAlbert et al, 2008 – current smokers, fewer years of formal education, lower income, lower occupational status
Where is prevalence higher for AD?
Ballart et al (2011), north america, europe, lower in se asia, india and africa
Is there a relationship between diet and AD?
Sjognen & Blennous 2005 – high fat/high chol diet = implicated in development of AD
Cholesterol improving drugs?
Sparks et al, 2005 - taking statin drugs to lower cholesterol also seems to offer some protection against AD
How many gene mutations contribute to early onset AD?
Ballard et al 2011 – 3
APP
PS1/PS2
APOE gene
APP gene mutations
chromosome 21. associated with 55-60 years.
Janichi & Dalton, 1993 – down syndrome people (Tripling of chrom 21) = who live past 40 = likely to develop illness like dementia
How much of cases do APP, PS1 and PS2 mutations account for?
5%
Where is PS1 and PS2 mutations?
Chrom 14. 30-50 years onset
What chromosome is the APOE gene on
Chromosome 19. apoliprotein
What does APOE gene code for?
Blood protein that helps carry cholesterol through bloodstream.
A person can inherit 0 1 or 2 of APOE-E4 gene == risk increasies accordingly
What did Ballard et al (2011) find re APOE?
HAving 2 APOE-E4 allleles results in 7 fold increase in person’s chance of developing disease
What did MAlaspine eta l 2002 find?
Approx 65% of patients have at least one copy of the APOE-E4 allele
4 fold increase in dvelopment of AD up to 5 years after traumatic brain injury
What did Myers et al, 2006 find?
Only 55% of patients with 2 APOE-E4 alleles had developed AD by 80
Weggen et al 2001
Exposure to non-steroiidal anti-inflammatory drugs e.g. ibuprofen may be protective and lead to lower risk of AD
What did FDA issue a warning about?
Schultz 2008 – patients with dementia who receive atypical anti-psychotic meds = incerased risk of death
Hiippocampal size and AD?
Heijer et al, 2006 – reduction in HIIP size predicts later development of AD in certain cases
Sperling et al 2003 – HIP = less active when patients with AD = enganged in mem tasks
What evidence is there against HIP size reduction and AD?
Smith et al 2002 – people at genetic high risk = incrased activity in various brain areas including the HIP when they engage in memory tasks
Maybe because APOE-E4 carriers have to work harder to manage cog tasks
Brain weight sta?
Perl, 1999 — by age 80, our brain has lost about 15% of original weight
Cost of dementia annualy?
Alzheimer’s association, 2010 – $172 billion. estimated
Caregivers of AD patients~?
Cummings et al, 2002 – caregivers sufffer from increased rates of depression and physical illness
Reducing length of stay of deliours patients?
Levkoff et al (1986) – reducing lenght of stay of delirous patients in hospital by a day = $1-2 billion savings annually.
Experiment in a cardiac intensive care unit?
Uguz et al, 2010 – cardiact intensive care unit, acute myocardial infections. 3 independently related predicitve factors
Old age
Higher serum potassium on admission
Cardiac arrest during myocardial infection
Which anti-depressant has been succesfully used to treat delirium?
Furose et al, 2010 –> fluvoxamine – rapid decrease in symptoms
When is the full benefit of disease modifying treatment posisble?
Carillo et al, 2009 – only obtainable if drugs = digven to paople so early in teh ‘pathological process’ of AD that clinical symptoms of thsi disease have not yet surfaced.
What can HIV and AIDS cause?
Irreversible dementia
Name three types of dementia?
Lews Body dementia
Vascular dementia
Dementia Pugilistic
What is Lews Body dementia?
1/7 dementia cases. Visual hallucinations. Parkinsonism symptoms. Lwo qualtiy of life. Dififcult to plan ahead.
Variable experineces from indivdiual to indivdiual
What is vascular dementia?
67000 people die from strokes each year.
Onset = more sudden than in AP. Outcome = similar to AP
Entirely different disease to AD in terms of underlying neuropathology = series of circumcised cerebal infarcts - ‘smal strokes’
Treatment = more encouraging than AD - basic problem of cerebral arteriosclerosis can me medially managed to some extent – decreases likelihood of further strokes
What is dementia pugilistics ?
Career boxers/people who receive multiple blows to head.
AVerage time of onset = 16 years after start of boxing
Muhammed Ali
Chris Beneit (WWE) killed wife and son and hung himself in June 07
Symptoms = dementia, parkinsonism or tremors, lack of co-ordination
Drake & Cifo (2004) – not well understood why it occurs
