Dementia Flashcards
What is mild cognitive impairment (MCI)?
early memory decline on formal memory tests (e.g. MMSE) (i.e. it cannot just be subjective) without clinical evidence of the other features of dementia
What can mild memory problems indicate in elderly people?
Dementia
Depression
Anxiety
Stress
Physical problem
What are the ways dementia can be classified?
Cortical
Subcortical
Progressive
1ry or 2ry
What is cortical dementia?
dementias causing problems with: memory, language, thinking and social skills
What is subcortical dementia?
dementias causing problems with: memory, emotions and movements
What is progressive dementia?
Dementia that deteriorates over time
What is the difference between 1ry and 2ry dementia?
1ry dementia has no alternative cause
2ry dementia occurs as a result of: physical disease or injury
How is Alzheimer’s dementia classified?
It is a: primary progressive cortical dementia
What are the types of dementia (with prevelances)?
7 types:
Alzheimer’s dementia (62%)
Vascular dementia (17%)
Mixed dementia (10%)
Dementia with Lewy bodies (4%)
Other causes (3%)
Parkinsons disease dementia (2%)
Frontotemporal dementia (2%)
How many people are affected at any one time by Alzheimer’s dementia (AD)?
500,000
Over what age are 98% of AD pts?
98% are over 65
What are the three types AD? (with their rarities)
Early onset (less than 10%)
Late onset (85%)
Familial (5%)
What is early onset AD associated with?
Myoclonus
What is the age at which early and late AD are split?
65
How much of the familial subtype of AD is inherited?
100%
At what age does familial AD normally onset?
in the 40’s
How does vascular dementia (VD) normally progress?
In a stepwise manner
What is mixed in mixed dementia?
A mix of AD and VD
How many people in the UK are affected by dementia with Lewy bodies (DLB)?
25,000
The symptoms of DLB are most similar to what type of dementia?
AD
Pt’s with DLB often show features of what?
Parkinsonism hallucinations
What are the causes of dementia under the umbrella term “Other causes” of dementia?
Creuztfeldt-Jakob disease
Huntington’s disease
Dementias due to high alcohol intake: Korsakoff’s syndrome AND alcohol-related dementia
Dementia related to reversible conditions: B12 deficiency AND hypothyroidism
What is Creuztfeldt-Jakob disease?
human form of mad cow disease caused by prions
What is Korsakoff’s syndrome?
Dementia due to lack of lack of thiamine (Vit B1)
What proportion of Parkinson’s disease pts are affected by dementia?
30% of parkinsons pts have dementia
What are the signs and symptoms of parkinson’s disease dementia most similar to?
DLB
For how long must a pt have had Parkinson’s before they can be diagnosed with Parkinson’s disease dementia?
The pt must have had Parkinson’s for 2 years before developing dementia to be diagnosed with Parkinson’s disease dementia
What is frontotemporal dementia?
It describes a range of dementias including picks disease
What age group + gender is frontotemporal dementia more common in?
Over 65’s
Equal in M + F
What are the early signs of frontotemporal dementia? (as opposed to)
Personality and behaviour changes (as opposed to memory decline)
What proportion of pts with mild cognitive impairment (MCI) develop dementia each year?
15%
How many people are their with dementia in the UK?
820,000
How much roughly does dementia cost the NHS each year?
£20 billion
What proportion of over 95’s have dementia?
1/3
What is the m:f split of dementia?
2/3 of dementia pts are female
Worldwide roughly how many people are affected by dementia?
20 million
How many over 65 year olds have dementia?
5%
How many over 80 y/o’s have dementia?
20%
Which dementias are more common in men than women?
VD
DLB
If your parent has dementia what is the likelyhood you will develop it?
Uncertain you will inherit it
If you do it is unlikely to present in the same way
What three genes are implicated in early onset AD? (and on what chromosomes are these on)
Amyloid precursor protein (APP) (chromosome 21)
Presenilin gene 1 (PSEN-1) (chromosome 14)
Presenilin gene 2 (PSEN-2) (chromosome 1)
What is the inheritance pattern of early onset AD?
Autosomal dominant
When should you screen someone for early onset AD?
If 2 or more relatives develop AD under the age of 60
To what is late onset AD linked to?
apolipoprotein E4 (APO-E4)
What are the respective risk increases of developing late onset AD if you have APO-E4?
If 1 copy = x4 risk of AD
If 2 copies = x10 risk of AD
What proportion of the population have 2 copies of late onset APO-E3?
60%
What proportion of pt’s who are homozygous APO-E3 will develop late onset AD?
50% by 80yrs
Which apolipoprotein (APO) is slightly protective for late onset AD?
APO-E2
What is the distribution of APO-E2 within the population?
1 copy - 11%
2 copies - 0.5%
What are the genetic sybtypes of VD and how common are they?
They are all rare
Cerebral Autosomal-Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL)
Hereditary Cerebral Hemorrhage With Amyloidosis (HCHWA)
Which gene is linked to CADASIL?
Notch 3
Which gene is linked to HCHWA?
APP gene
How is Down’s syndrome linked to AD?
As the Amyloid precursor protein is located on chromosome 21 and it is linked to AD via APO-E4 downs have a trisomy of chromosome 21
What is the increase in risk of AD in Down’s syndrome?
50% of 50-60 y/o’s
What is the inheritance pattern of Huntington’s disease?
Autosomal domiant
When do pts with Huntington’s disease typically develop dementia?
Earlier on than a normal person
How heritable is frontotemporal dementia and which gene is implicated?
Very heritable
Faults on the: Tau gene
What characterises AD?
loss of neurons and synapses from the cerebral cortex
and certain subcortical regions
causing gross atrophy
Which areas of the brain are mainly affected in AD?
temporal lobe (especially the hippocampus)
parietal lobe
parts of the frontal cortex
cingulate gyrus
What area is affected earliest in AD?
The hippocampus
What are the two abnormal structures found in AD? (inside or outside cells)
Amyloid plaques (outside cells)
Neurofibrillary tangles (inside cells)
How are amyloid plaques thought to cause cause cell death?
block cell-to-cell signalling
or
activate immune system responses that trigger inflammation and cell death within the brain
What form the amyloid plaques?
amyloid precursor protein abnormally forms Beta-amyloid which stick and clump together
How are neurofibrillary tangles thought to cause cell death in AD?
Tau usually helps the strands of the transport system link together
so when faulty the transport system can no longer do its job
thus the cells dies
Are amyloid plaques and neurofibrillary tangles pathognomonic for Alzheimer’s disease?
No they also occur as a normal part of ageing
What is the frontal lobe responsible for?
Voluntary motor activity
Speaking ability
Complex thought
Personality
What will a deficit in the frontal lobe cause?
Problems with:
Initiating action (due to problems with voluntary motor activity(
Complex thought
Inhibition (due to changes in personality)
What is the parietal lobe responsible for?
Processes sensory information
Sequence of actions
Proprioception
Calculation and construction
What will a deficit in the parietal lobe cause?
Problems recognising faces and objects (as processes sensory information)
difficulty in carrying out a sequence of actions (as parietal lobe sequences actions)
What is the temporal lobe responsible for?
Attention
Recording and storing verbal and visual memory
Learning of information
What will a deficit in the temporal lobe cause?
diminished attention
difficulty with short term memory
difficulty producing speech
What are the functions which experience progressive decline in dementia?
Memory
Cognitive function
Awareness of the environment
Decline in emotional control
How long should symptoms be present for before dementia should be diagnosed?
6 months
What are the early signs of dementia?
1) Short term memory loss (the earliest symptom)
2) Repetition of questions
3) Difficulty embracing change
How long do the early signs of dementia usually last for?
3-4 years
What are the levels of functioning in the varying degrees of dementia progression?
Early - independent
Middle - achieves some ADLs
Late - dependant
What are the middle signs of dementia?
1) Failure to recognise people
2) Difficulty with daily tasks
3) Needs prompting
What are the late signs of dementia?
1) Incontinence
2) Aggression
3) Decline in speech
4) Weight loss
How long do patients typically last in the late stage of AD?
1-2 yrs
What is the mean life expectancy following a diagnosis of AD?
7yrs
How similar are the symptoms between pts with AD?
They vary quite a lot
What is the common cause of death of AD pts? (what is a big contributing factor)
Pneumonia (malnutrition due to AD)
Which has a worse prognosis; AD or VD?
VD
What are the types of VD?
1) Post-stroke dementia
2) Multi-infarct dementia
3) Subcortical vascular dementia
4) Mixed cortical and subcortical dementia.
How much higher is the risk of VD in those that have had a stroke?
9x
A year after a stroke what % of pts develop dementia?
25%
How does multi-infarct VD progress?
in a step wise decline following a series of small strokes in the cerebral cortex (cortical vascular dementia)
Which type of dementia is more typically of pts with HTN?
Subcortical vascular dementia
What causes subcortical vascular dementia? (if widespread what is this called)
Ischaemic damage causes demyelination of nerve sheaths i.e. white matter (Binswanger’s disease)
What are the two typical symptoms in VD?
Memory problems less apparent earlier on
‘Step wise’ progression
What is the diagnostic criteria for VD called?
NINDS-AIREN
What are the diagnostic criteria for VD?
1) Memory impairment and impairment in a further cognitive domain (as for AD)
2) Deficits should be causing limitation with Activities of Daily Living (ADLs) not due to the physical effects of stroke alone
3) Evidence of cerebrovascular disease on clinical examination and imaging
What is the core criteria for diganosing AD?
1) Evidence of impairment of memory + at least one of:
- Language impairment
- Apraxia
- Agnosia
2) Present for >6 months
What is the curative treatment for DLB? (what treatments can be used at all)
There is none (NICE recommend a trial of AChEi’s)
What is the average and range of life expectancies for DLB?
Average = 5-7 yrs
Range = 2-20 yrs
What is the management of DLB focused on?
managing neuropsychiatric disturbances and movement disorders
What are Lewy bodies made up of?
the protein: alpha synuclein
How do Lewy bodies disrupt the brain?
They interrupt the action of ACh and dopamine at the nuronal synapses.
What are the two domains that Lewy bodies are found in? (what are they called)
The substantia nigra (classical Lewy bodies)
In the cortex (cortical Lewy bodies)
Where are Lewy bodies found in Parkinson’s disease?
In the substantia nigra thus they are classical Lewy bodies
Which areas of the cortex shrink in DLB?
parietal lobes
temporal lobes
cingulate gyrus
What causes the formation of Lewy bodies?
Its unknown
What are the core features of DLB?
1) Fluctuating cognition (although this does get progressively worse)
2) Features of parkinsonism
3) Visual hallucinations
How can the fluctuating cognition in DLB confuse clinicians?
It can be as extreme as to cause stupor which can lead to clinicians hunting for a different explanation than that of DLB?
Describe the nature of visual hallucinations in DLB?
Complex and detailed
not always destressing
What normally accompany visual hallucinations in DLB?
delusions
What are common supportive features of DLB?
Sensitivity to neuroleptics (antipsychotics) inducing parkinsonism
REM sleep behaciour disorder (RBD)
What is the worst case scenario in giving pts with DLB neuroleptics?
A fatal neuroleptic malignant syndrome
What is REM sleep behaviour disorder?
During REM sleep pt will: move gesture and/or speak
What is an early sign/risk factor for DLB?
REM sleep behaviour disorder (RBD)
How many ADLs should be affected before diagnosing DLB?
2 ADLs
How many people does frontotemporal dementia affect?
1 in 5000
What is the youngest age group frontotemporal dementia (FTD) can affect?
Although rare it can affect 20-30 y/o’s
What is the length of survival of pts with FTD?
10-15 years
What is the curative treatment for FTD?
There is none
How should behavioral symptoms be medically managed in FTD?
antidepressants and
consideration for atypical neuroleptics
Which medications should not be used in FTD + why?
Acetylcholinesterase inhibitor drugs used in Alzheimer’s, such as donepezil
may worsen the condition
What is the underlying pathological process in FTD?
Abnormal Tau protein aggregation
What are the typical changes in FTD (how may this manifest)?
Changes in:
1) personality and behaviour (person becoming increasingly more extrovert and disinhibited)
2) Language problems (reduced speech)
3) Pt’s overindulge (Hyperphagia)
What are the neurological signs seen in FTD?
Primitive reflexes may develop:
- Palmar grasp relex
- Rooting reflex (Move face towards a stimulus, for breast feeding)
What is the standard criteria used for FTD diagnosis called?
Lund-Manchester criteria
How is Parksinsons disease dementia (PDD) and Dementia with Lewy bodies (DLB) differentiated?
PDD - few years of unilateral parkinsons before dementia symptoms
DLB - A year of bilateral signs and cognitive decline before parkinsons symptoms
What is the issue trying to treat PDD and LBD (with subsequent Parkinson’s)?
L-DOPA (the treatment for parkinsons) can exacerbate dementia symptoms /psychotic symptoms
The antipsychotics can exacerbate the Parkinson’s symptoms
Which medications should especially be avoided in PDD?
Haloperidol
chlorpromazine
sulpiride (an antipsychotic)
What are the two management principles for medications in AD?
1) Treatment to enhance cognitive function
2) Treatment of behavioural and psychological symptoms of dementia (BPSD)
What are the two types of medication licensed for AD? (and what do they help with)
- Acetylcholinesterase inhibitor
- NMDA receptor antagonist (May help slow cognitive decline and control symptoms)
What are the three acetylcholinesterase inhibitors currently available?
Donepezil (Aricept)
Galantamine (Reminyl)
Rivastigmine (Exelon)
How do acetylcholinesterase inhibitors work?
They inhibit the breakdown of acetylcholine which is important in cognitive processes
What is the name of the NMDA receptor antagonist licensed for AD?
Memantine
Where does memantine have its affect and how does it work?
It blocks the NMDA glutamate receptors
At normal levels, glutamate aids in memory and learning
but if levels are too high (as in dementia), it leads to overstimulation of nerve cells resulting in degeneration
What are the behavioural/mental mimics of dementia?
- delirium
- learning disability
- depression
(4. Diogenes syndrome)
What are the groups of physiological mimics of dementia?
1) Medications s/e’s
2) Metabolic
3) Nutritional
4) Infections
5) Subdural haematomas
6) Poisoning
7) Tumours
8) Normal pressure hydrocephalus
What are the metabolic mimics of dementia?
Hypothroidism
What are the nutritional mimics of dementia?
Vit B12 deficiency
Thiamine deficiency (Vit B1) due to alcoholism.
Pellegra (Vit B6 deficiency) can cause confusion mimics dementia
What are the infectious mimics of dementia?
Syphillis + AIDs can cause dementia
Lyme disease can cause memory loss
What are the poisonous mimics of dementia? (do these resolve)
Lead + other heavy metals
Recreational drugs
Alcohol
(All may persist, substances can cause “substance induced persisting dementia”)
How can tumours lead to dementia?
Due to direct damage and
from release of toxins
What are the classic symptoms see in normal pressure hydrocephalus?
There is a classic triad:
Worsening confusion
Abnormal gait
Urinary incontinence
For what stages of AD are the three acetylcholinesterase (AChE) inhibitors indicated?
Mild to moderate AD
For which AD pts is memantine indicated for?
Pt’s with moderate AD who cannot take AChE inhibitors
OR
Pt’s with severe AD
Which AD medications should GP’s start pt’s on?
Should only be a specialist who starts AD medications
What is the mainstay of treatment for behavioural + psychological symptoms of dementia (BPSD)?
Non-pharmacological treatment
What is the best antipsychotic for BPSD generally?
Respiradone
Which type of dementia should care be taken in when prescribing antipsychotics?
DLB
PDD
What do antipsychotics increase the risk of in dementia pts?
Sedation
falls
parkinsonism
Stroke x3 (even higher if >80)
In DLB what can be used to treat BPSD?
Rivastigmine (a parasympathomimetic)
What is the issue with using TCA’s in dementia?
They can affect cognition
Who should prescribe antipsychotics to elderly pts?
Geriatricians
or
Old age psychiatrists
