Dementia

Question 1

How is dementia defined?

Answer 1

the loss of cognitive ability in a previously unimpaired person beyond what might be expected from normal ageing. It is a collection of disorders grouped due to the similar nature of impairment that results from different causes. People with dementia have significantly impaired intellectual functioning that interferes with normal activities and relationships. They also lose their ability to solve problems and maintain emotional control, and they may experience personality changes and behavioral problems, such as agitation, delusions, and hallucinations.

Question 2

What are the DSM criteria for Dementia diagnosis?

Answer 2

1. Evidence of Amnesia (memory impairment) + at least one of:
   - Aphasia: (receptive/ expressive) Language impairment e.g. word finding difficulty
   - Apraxia: motor disorder where the individual has difficulty with the motor planning to perform purposeful tasks or movements when asked even when motor and sensory function are maintained. Also impaired visuo-spatial ability- e.g. forget where place items, get lost in familiar places.
   - Agnosia: inability to process sensory information to allow for recognition (e.g. visual- unab to recognize visually presented objects/ faces).
   - Impairment of executive functioning: diff perform complex tasks/ planning ahead, abstract reasoning impaired. (poor safety awareness, diff dressing bc cannot follow order of things)
2. Impairment of functioning
3. No other medical or psychiatric explanation
4. Present for at least six months
5. Progressive decline depending on type will be gradual (AD/ multi-infarct vascular) or acute onset (vascular)

For vascular dementia dx to be made, there must be evidence of cerebrovascular disease on examination and imaging and limitation of patient to carry out ADLs not due to physical effects of stroke alone.

Question 3

What is MCI (Mild Cognitive Impairment)?

Answer 3

When there is evidence of early memory decline on formal memory tests (e.g. MMSE) without clinical evidence of the other features of dementia. This may progress to dementia but also could be a feature of depression, anxiety, or a physical illness. It cannot be diagnosed without conducting a formal memory test. 10-15% will go onto develop dementia each year.

Question 4

What is the epidemiology of dementia?

Answer 4

M:F 1: 2

The prevalence is 5% over the age of 65 and 20% over 80 and 33% over 95s have dementia

Question 5

What are the classification possibilities for dementia?

Answer 5

1. Primary- dementia that is not secondary to other causes
2. Secondary- dementia due to physical illness or brain injury
3. Progressive- deteriorating function over time
4. Cortical- issues with memory, language, thinking and social skills
5. Subcortical- issues with memory, movement, emotions

Question 6

What are the causes of dementia? (Not the types)

Answer 6

1. Trauma: head injury, boxing
2. Degenerative changes: Alzheimer’s disease, frontotemporal dementia, lewy body dementia, parkinson’s disease, Huntingdon’s disease, Progressive supranuclear palsy.
3. Malignancy: intracranial primary, mets
4. Vascular: multi-infarct, cerebral infarcts, binswanger’s disease, Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL)- get strokes and white matter changes, vasculitis
5. Anoxic: post cardiac arrest
6. Endocrine/ metabolic/ toxic: alcohol, heavy metals, drugs, hypothyroid, folate and thiamine deficiency, paraneoplastic, inherited e.g. Wilson’s
7. Infections: syphilis, HIV, Creutzfeld Jakob Disease, Sclerosing panencephalitis (SPE), cryptococcus

Question 7

What are the main dementia types?

Answer 7

1. Alzheimer’s: most common, affecting about 60%. Risk increases with age.
2. Vascular: second most common, about 17%. sometimes progresses stepwise manner (stable disease then sudden deterioration). Higher mortality than AD.
3. Mixed: usually mix of 1. and 2. affecting 10%
4. Lewy Bodies: 4% similar symptoms to Alzheimer’s but also may have features of Parkinson’s (but these are concominant with dementia symptoms) and hallucinations.
5. Frontotemporal: 2% usually affects personality and behaviour predominantly before affecting memory
6. Parkinson’s disease: 2% v similar to Lewy Body Dementia however dementia is developed at least 12m after development of symptoms of Parkinsonism
7. Other: 3% e.g. HD, Creutzfeld Jakob, alcohol or B12 deficiency induced, CADASIL (inherited type of Vascular dementia), HIV, Dementia Puglistica (head injury/ trauma- repeated), Down’s Syndrome.

Question 8

What is memantine? When is it used?

Answer 8

Glutamate R (NMDA) antagonist (irreversible) to reduce Glutamate excitotoxicity. At normal levels, glutamate aids in memory and learning, but if levels are too high, it leads to overstimulation of nerve cells resulting in degeneration.
It is used following the unsuccessful trial of acteylcholinesterase inhibitors in moderate AD/ for use in severe Alzheimer’s Disease. It cannot be used prior to the trial of acetylcholinesterase inhibitors because it irreversibly binds to Glutamate R, AchE will be ineffective if used after a trial of memantine.
Not curative but may slow the progression of disease
SE: nausea, restlessness, headache, stomach ache
Tx to be continued only when having a worthwhile effect on cognitive, global, functional or behavioural symptoms.

Question 9

What are the Behavioural and Psychological Symptoms of Dementia (BPSD)? How are they usually managed?

Answer 9

BEHAVIOURAL:
Apathy, Agression, Wandering, Restlessness, eating problems, agitation, disinhibition, pacing, screaming, sundowning.
PSYCHOLOGICAL:
Depression, Anxiety, Insomnia, Delusions, Hallucinations.

AD most common: anxiety, apathy, depression, irritability, agitation
Vascular most common: apathy, depression, delusions
Frontotemporal most common: elation, apathy, delusions, disinhibition.
Lewy Body most common: depression, sleep disturb, delusions, hallucinations.

1. Risperidone is the only antipsychotic licensed for the tx of BPSD and it is licensed for 6w.

Question 10

What is pseudodementia?

Answer 10

presentation with memory loss that is caused by depression,

Question 11

What are some of the genetic causes of Dementia?

Answer 11

1. Trisomy 21: 50% will develop AD by 60
2. Early onset dementia (30-40s) is developed if patient possess APP, PSEN-1 or PSEN-2 genes that are inherited in an autosomal dominant fashion.
3. Frontotemporal highly heritable- likely to do with tau
4. posession of APO-E4 (apolipoprotein E) increases chance of AD. 1 copy of gene, 4x more likely develop. 2 copies, 10x more likely to develop. APO-E3 is also a risk factor. APO-E2 appears to protect patients.
5. Vascular dementia: Notch3 gene is linked with CADASIL ; hypercholesterolaemia, HT, DM all have some genetic component and increase chance of vascular dementia.

Question 12

What are the RF for the development of Dementia?

Answer 12

1. Vascular: DM, HT, Smoking (increases risk of mental decline also), Hypercholesterolaemia (and Atherosclerosis)- statins don’t reduce risk, lack of physical activity, diet high in saturated fat
2. Mild Cog Impairment: MCI
3. Genetics
4. Age- particualrly for AD and Vascular Dementia
5. Binge drinking

Question 13

How does Donepezil act? What is it used to treat? Name another drug in it’s class. What are the SE?

Answer 13

Reversible Achetylcholinesterase inhibitor therefore increases Ach levels and it’s action.
It is used in the treatment of Dementia and is used first line before the use of Memantine. Used in mild- moderate Alzheimer’s Disease.
Rivastigmine and Galantamine are other drugs in this class.
SE: main ones are GI upset- n + v, diarrhoea, muscle cramps, sleep disturbance.
Not curative but may slow the progression of disease

Question 14

What is the prognosis for AD? What are the different forms of Alzheimer’s Disease?

Answer 14

7 years average. less than 3% live beyond 14y of diagnosis.
1/ Early Onset: rare, less than 10% cases. associated with development of myoclonus
2/ Late Onset: most common, symptoms usually present at 65.
3/ Familial: rare, very early onset usually in 40s, less than 5% of cases, totally heritable.
As people reach 80yo, 1 in 6 are affected (from 1 in 14 at 65).

Question 15

What characterizes the early phase of dementia?

Answer 15

minor changes in abilities/ behaviour- may only notice in retrospect
loss of recent memory, repetition of Q, slow at grasping ideas, occassional confusion/ disorientation, mislaying items and blaming others
unwilling to embrace change
errors of judgment
commonly lasts about 3-4 years

Question 16

What characterizes the middle phase of dementia?

Answer 16

• early changes become more pronounced and they begin to require more support to complete ADLs tasks even those that are familiar e.g. buying food, prep meals
• decline in language
• prompting required bc increasingly forgetful
• increasing repetitive activities/ speech due to reduction of short term memory
• fail to recog friends/ extended family
• disorientation to time, place and person
• frustration may lead to aggression/ loss of confidence
• may develop hallucinations
• memory for distance past often remains good
• wandering and agitation may develop

Question 17

What characterizes the late phase of dementia?

Answer 17

final 1-2 years

• increased dependence on others for care- require intensive support for basic hygiene, feeding etc
• inab to recognize familiar objects/ relatives
• increased frailty - confined to wheelchair/bed
• poor appetite, dysphagia, weight loss- malnutrition common and contrib to risk of infection (often cause of death)
• deteriorating speech and understanding
• incontinence
• difficulties with psychomotor skills and movement
• restless, agitated, distressing, aggressive behaviour.

Question 18

What are some of the findings in the brain of someone affected by AD?

Answer 18

1. Early atrophy of the hippocampus- area of memory formation
2. cortical atrophy- involved in planning, thinking and remembering.
3. degeneration of frontal cortex, parietal lobe and temporal lobes, cingulate gyrus.
4. ventricular enlargement
   Loss of neurones and synapses due to the abnormal aggregations of: tangles and plaques (more than that seen in normal aged brains).
   - Plaques: beta amyloid aggregates blocking cell-cell signalling/ activating immune system to trigger inflammation and cell death.
   - Tangles: composed of Tau fragments, that disrupt cell transport via microtubules causing cell death.

Question 19

What are the two main theories of the pathophys in Alzheimer’s Disease?

Answer 19

1. Cholinergic hyp: AD caused by reduced Ach synthesis but meds are not v effective
2. Amyloid Beta hyp: Amyloid Beta deposits are to blame for the development of AD. Supported by the high rates of development of AD in people with trisomy 21 (Amyloid Beta Precursor Protein is found on Chr 21), and APO-E4 increases AB protein amounts and significantly increases risk of AD. But vaccine clearing Amyloid B plaques had no effect on dementia. Update of T- perhaps a fragment of Amyloid B is to blame instead.
3. Tau hyperphosphorylation disrupting Microtubules, cell transport therefore cell signalling and causing cell death.
4. Inflammation: AD results in 70% loss of NA producing cells in Locus Coerulus. NA is thought to be anti-inflammatory, bathing neurons etc in neocortex/ hippocampus. NE is thought to stim glial cells to phagocytose Amyloid Beta.
5. Herpes Simplex Virus 1
6. Myelin breakdown
7. Oxidative stress

Question 20

What are the subtypes of vascular dementia?

Answer 20

1. Post-stroke: following acute stroke
2. Multi-infarct: step wise progression following mini strokes in the cortex
3. Subcortical: HT association due to demyelination of nerve sheaths
4. Mixed subcortical and multi-infarct.

Question 21

What are the findings in the brain of someone suffering from Dementia with Lewy Bodies?

Answer 21

Protein aggregates of Alpha Synuclein in the cytoplasm which interrupts the action of Ach and DA. Areas particularly affected:

1. Substantia Nigra (as seen in Parkinson’s DIsease)
2. Cortical Lewy Bodies
3. Atrophy of parietal, temporal lobes and cingulate gyrus.
4. Loss of Ach prod neurones in nucleus basalis, sim to AD.

Question 22

What are the core and supportive features of Lewy Body Dementia? What is required for a dx of Lewy Body Dementia?

Answer 22

CORE: Parkinsonism, Fluctuating cognition/ alertness, visual hallucinations- complex and detailed
- 2 of the CORE features must be satisfied for a diagnosis to be made.
SUPPORTIVE: Falls, sensitivity to neuroleptics (may develop Parkinsonism/ Fatal Neuroleptic Syndrome), REM Sleep behaviour disorder, syncope/ Autonomic Abnormalities e.g. postural hypotension

Question 23

How do you differentiate Lewy Body Dementia from Parkinson’s Disease dementia?

Answer 23

In Lewy Body Dementia, cognitive symptoms appear within 2 years of the motor symptoms whereas in PDD, they appear much later.

Question 24

What are the brain findings consistent with Frontotemporal Dementia and presentation?

Answer 24

Focal atrophy in the frontal and temporal lobes. Memory impairment is rarely the presenting feature (occurring typically later in the disease), instead see marked change in personality (e.g. disinhibition), behaviour (overeating), emotion (frontal lobe damage) and language (due to damage in temporal lobe). May get release of primitive reflexes e.g. grasp.

Question 25

What is Frontotemporal Dementia? Remember the patient you saw with this condition..

Answer 25

Usually affects people aged 65 or younger. No tx for it but management of behaviour is v important partic to reduce cg burden using antidepressants/ antipsychotics.
Duration of 10-15 years, some evidence of heritability.
Donepezil may worsen the condition (partic behavioural symptoms while providing little improvement in memory).
Protein aggregation occurs primarily in frontal and temporal lobes and these are composed of tau.
Includes early loss of insight, impairment in personal regulation and social interpersonal conduct and emotional blunting.
Insidious onset and progressive.
Behavioural change: reduced self-care, overeating/ hyperorality, distractibility, mental rigidity.
Speech: mutism, reduced spontaneity of speech, echolalia- repeating what you’ve said, perseveration- repetition of speech/ gesture w/o stimulus, economy of speech
Examination: primitive reflexes, tremor, low BP, akinesia- impaired/lost voluntary movement, incontinence
Investigations: FL testing abnormal, no amnesia/ perceptual deficits, imaging- abnormalities confined to frontal and temporal lobes.

Question 26

Parkinson’s Disease Dementia- what symptoms favour this diagnosis over Lewy Body Dementia? What meds should be avoided/ used with caution in Parkinson’s Disease Dementia?

Answer 26

• Unilateral symptoms of PD for more than 2 years before any cognitive decline is evident. Bilateral and early cognitive decline favours LBD.
• some meds for PD are thought to exacerbate dementia.
• Mixed pathology is common with either VaD/ AD being present on autopsy.
• Psychotic symptoms may be exacerbated by Anti-PD meds and therefore these should be withdrawn/ reduced but this will increase disability by worsening Parkinson’s symptoms.
• Neuroleptics e.g. Haloperidol, Chlorpromazine, Sulpiride should be avoided because they have sub risk of EPS and worsen Parkinson’s symptoms.

Question 27

What are the common presenting complaints in Parkinson’s Disease Dementia?

Answer 27

Marked Forgetfulness, lethargy, loss of executive functioning, may see loss of emotional control

Question 28

If someone’s parietal lobe is affected, what are you likely to see deficits in?

Answer 28

Problems recognising faces and objects and difficulty in carrying out a sequence of actions, clumsiness.

Question 29

If someone’s frontal lobe is affected, what are you likely to see deficits in?

Answer 29

Problems with inhibition, initiating action, reasoning and abstract thought.

Question 30

If someone’s temporal lobe is affected, what are you likely to see deficits in?

Answer 30

Problems cause poor attention, difficulty with short term memory and producing speech.

Question 31

What are the ddx for Dementia?

Answer 31

1/ pseudodementia: Depression
2/ Meds: steroids, antidepressants
3/ Metabolic: hypothyroid, vitamin B12 deficiency
4/ Nutrition: Thiamine (B1) deficiency results from chronic alcoholism, severe deficiency of B6 can cause Pellegra, which may include confusion
5/ Infection: HIV, Syphilis (untreated), Hep C, Lyme Disease rarely causes memory loss
6/ Trauma: subdural haematoma
7/ Tumour: Glioblastoma- confusion due to direct damage and release of toxins
8/ Poisons: heavy metals, recreational drugs
9/ Other: Normal P hydrocephalus (triad- incontinence, confusion, ataxia)

Question 32

What are important things to elicit in the history of a patient with ? dementia ? delirium?

Answer 32

1. Onset and progression
   - sudden onset (Hrs-Days) with quick progression usually suggests delirium however, weeks- subdural haematoma, normal pressure hydrocephalus, metabolic derangement, drug induced, space occupying lesion.
   - stepwise might indicate vascular cause
2. Memory, Mood, Personality, Behaviour, ADLs.
3. A + D use, CVD risk factors, OTC, Meds.

Question 33

What is important to cover in systems review when a patient presents with Dementia? What physical examinations would you want to focus on in a patient presenting with dementia?

Answer 33

1. physical health generally
2. sleep
3. appetite and weight
4. mood
5. incontinence/ falls
   - CVD: AF, HT, Bruits all increase risk of vascular dementia
   - neurological examination both gait and hands for tremor, ataxia (PD) , myoclonus (CJD), chorea (HD)
   - Cranial nerves examination: rule out space occupying lesion, examine hearing and vision
   - thyroid: hypo/er can cause confusion
   - liver: chronic liver disease/ alcoholic liver disease can cause confusion

Question 34

What is assessed when asking patients to name as many animals as they can within a minute? What about words beginning with a certain letter? What about the clock face?

Answer 34

Fluency. Specifically verbal (words) and semantic (animals)
Executive function (Frontal Lobe) to carry out task in correct steps and abstract conceptualisation and visuospatial

Question 35

What are the investigations important for a suspected case of dementia?

Answer 35

1. Bloods: U+E, FBC, ESR, LFTs, TFTs, Lipids, Glucose, Vitamin B12, folate, Ca2+
2. ECG: baseline and screen for cardiac abnormalities
3. Imaging: CTB first line but MRI shows volume loss and SPECT shows perfusion, DAT- DA loss in sub niagra
4. Serology: HIV, Syphilis, Hep C but not routine
5. Cog Screening: ACE-R, MOCA
6. MSU if concerns about delirium

Question 36

How should vascular dementia be treated?

Answer 36

• reduce vascular risks: HT control, DM control, control AF, statins
• acetylcholinesterase inhibitors and memantine should not be prescribed for the treatment of cognitive decline

Question 37

How should Dementia with Lewy Bodies be treated?

Answer 37

Donepezil is thought to help with non-cognitive symptoms that challenge
very careful with antipsychotics bc more at risk of neuroleptic sensitivity reactions and extrapyramidal SE and severe physical deterioration.

Question 38

What is the management of BPSD (behavioural psychological symptoms of dementia)?

Answer 38

1. non-pharma: observe patient and get collateral hx, is their behaviour due to unmet need/ physical health issue/ misidentification, do they have a psych/physical hx, what is their relationship w/ carer etc.
   - ensure vision and hearing ok
   - help them with orientation
   - if patient hallucinating do not outright rebuke
   - encourage communication, slow own speech, give positive non verbal cues
   - involve family/ cg
   - provide familiarity to patient e.g. own music etc
   - encourage mobility
   - respite for cg
2. pharma management
   - agitation due to constipation: senna
   - agitation/ aggression due to psychosis: risperidone but increases stroke risk 3x and increases risk of falls, sedation, and parkinsonism (be careful in Parkinson’s Lewy Body dementias)
   - depression: citalopram / SSRIs (TCAs have anticholinergic activity which affects memory)
   - shouting due to pain: paracetamol
   - sleep disturbance: zopiclone
3. support at home: meals on wheels, respite, day centre, help with ADLs, specific home adaptations, care home placement, assessment for cg for their own needs.