Management of Dementia - chnact.org.au CGP 6. Dr... · Management of Dementia ... Medications:...
Transcript of Management of Dementia - chnact.org.au CGP 6. Dr... · Management of Dementia ... Medications:...
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Management of DementiaDr Mary Ann Kulh, GeriatricianCalvary Public Hospital Bruce, ACT
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Patient 1
82 year old lady with gradual onset of “short term” memory loss (e.g. misplaces keys, forgets appointments, repeating herself)
History of hypertension Medications: irbesartan 150mg mane, aspirin 100mg mane MMSE 22/30 (5 lost in orientation, 3 in recall)
What is the diagnosis and what do you do now?
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Patient 1
Bloods – EUC, FBC, B12, TSH all normal CT brain – moderate cerebral atrophy with predominance in
frontal and temporal lobes. Mild small vessel chronic small vessel ischaemic change.
What should be done now?
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Patient 1
Bloods – EUC, FBC, B12, TSH all normal CT brain – moderate cerebral atrophy with predominance in
frontal and temporal lobes. Mild small vessel chronic small vessel ischaemic change.
What should be done now?
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Medications for Alzheimer’s Dementia
Acetylcholinesterase inhibitors (AchEI) for mild to moderate Alzheimer’s dementia Donepezil (Aricept) Rivastigmine (Exelon) Galantamine (Reminyl)
NMDA receptor antagonists (memantine) for moderately severe AD
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Produce modest symptomatic benefits in some patients (cognition, function, behaviour)
Benefits are temporary None cure the disease or stop progression Studies currently targeting novel pathogenic pathways in
dementia
Medications for Dementia
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Cholinergic Theory of Alzheimer’s Disease Acetylcholine deficiency observed in post-mortem
examination of brains in advanced Alzheimer’s Destruction of cholinergic neurons and resultant
acetylcholine deficit thought to explain cognitive deficits in AD
More recent studies suggest cholinergic activity may not be reduced in early AD, and may even be up-regulated
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Cholinesterase Inhibitors
Only subsidised on PBS for Alzheimer’s Disease Diagnosis must be confirmed by a specialist Specialist or GP can write authority prescription for 6
months treatment, quoting initial MMSE or ADAS-cog score. Up to 2 months supply approved by phone, remainder by
written request
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Cholinesterase Inhibitors
Repeat MMSE (best done at 3 - 4 months after starting treatment) must improve by 2 points (or ADAS-cog by 4) to qualify for treatment beyond the first 6 months. Written authority prescription by specialist or GP.
Subsequent prescriptions by Streamline Authority 4219; no MMSE required to continue therapy.
New application required if switching from one cholinesterase inhibitor to another
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AD diagnosis confirmed by Specialist
MMSE < 10Meet PBS criteria
Baseline CIBIC+
MMSE 10-24
Written PBS authority
Within 6 months repeat baseline test
MMSE ↑ ≥ 2 pointsADAS-cog ↓ ≥ 4 points
CIBIC > much improved
Ongoing PBS authority
MMSE ≥25
Baseline ADAS-cog preferred but not
essential
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Cholinesterase Inhibitors: Contraindications Known sensitivity to drug Sensitivity to piperidine derivatives (donepezil) –
loperamide and fentanyl Prescribe with caution to patients with:
Sick-sinus syndrome or other cardiac conduction abnormalities
Moderate to severe asthma or COPD Seizures active gastrointestinal disease, or in patients receiving
non-steroidal anti-inflammatory agents
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Cholinesterase Inhibitors: Side-effects
Diarrhea, vomiting, nausea, fatigue, insomnia, and anorexia, but in most cases, such side effects are mild and decline with continued use of the drug.
Rivastigmine: One case of severe vomiting with oesophageal rupture reported to have occurred after re-initiation of treatment at an inappropriate single dose of 4.5mg following interruption of treatment for eight weeks.
Galantamine: three times as many people died while on the drug as those on placebo
Monitor for gastrointestinal symptoms and weight loss
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Memantine
Neurotransmitter glutamate plays an integral role in learning and memory
In AD abnormal glutaminergic activity can cause neuronal toxicity and may impair learning
Memantine blocks abnormal glutamate activity Memantine slows cognitive and functional loss in moderately
severe AD (MMSE 5-14)
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Memantine: Mechanism of Action
Glutamate excitotoxicity via excessive N-methyl-d-aspartate(NMDA) receptor excitation believed to play role in neuronal death in AD
Excitotoxicity occurs in part because of overactivation of NMDA-sensitive glutamate receptors, permitting excessive Ca2+ influx through the receptor’s associated ion channel
NMDA receptor antagonists may prevent neuronal loss associated with glutamate associated excitotoxicity
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Memantine Indications
Moderately severe Alzheimer’s dementia Following indications approved by PBS:
1. MMSE 10 – 14 2. MMSE ≤ 9 with Clinicians Interview Based Impression of
Severity (CIBIS) scale
Needs to be sole PBS subsidised therapy for the indication Can use in conjunction with cholinesterase inhibitors but only
memantine will be PBS subsidised
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Patient 2
62 year old retired office clerk Husband deceased Two daughters with separate Enduring Power of Attorney Travelled extensively Family history of dementia in 7 of 12 siblings Non-smoker, no regular EtOH
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Presenting Complaint
Visual neglect Difficulty perceiving objects on right side Veering to right hand side of road onto oncoming traffic (Jan
2010)
Visual agnosia Inability to distinguish contents of the fridge
Dressing apraxia Wearing clothes back to front
Mild expressive dysphasia Onset October 2009 MRI brain 2010 reported as “age related atrophy”
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Past Medical History
Osteoarthritis – bilateral hip replacements postoperative visual
hallucinations and delirium (Hb 89)
Hypertension and postural hypotension
Hypercholesterolaemia Vitamin D deficiency
Medications: Aspirin 100mg mane Nifedipine XR 30mg mane Cholecalciferol 1000units
mane Meloxicam 15mg mane PRN (Atorvastatin ceased Mar
2011)
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Physical Examination
BP 154/82mmHg PR 72 lying, 160/88mmHg PR 72 standing 1 min
Left sided visual neglect on confrontation but normal visual fields
No oculomotor palsy Normal power, reflexes, Babinski reponse on right
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Addenbrooke’s Cognitive Examination
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Addenbrooke’s Cognitive Examination
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Addenbrooke’s Cognitive Examination
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Cognitive Assessment
Addenbrooke’s Cognitive Examination Score 65/100, MMSE component 23/30 Deficits in visuospatial skills (inability to copy
intersecting pentagons or cube) Clockface – numbers crowded to right Perceptual abilities – unable to count dots, unable to
identify letters of alphabet Some deficits in memory and verbal fluency
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Posterior Cortical Atrophy
• Clinical features:• distinct clinical syndrome
• not just Alzheimer's disease (AD) with prominent visual defects
• Presents with progressive decline in complex visual processing out of proportion to other cognitive difficulties
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Posterior Cortical Atrophy
• clinical features:• mean age of onset 58 years (range 51-64)• progresses over a decade or more• visuoperceputal and visuospatial impairments in setting
of normal ophthalmological assessment• complex visual disturbances:
• visual agnosia• environmental disorientation• dressing apraxia• pure alexia• achromatopsia
Hiding in plain sight: a closer look at posterior cortical atrophyBeh SC, Muthusamy B, Calabresi P, et alPract Neurol 2014;0:1–9
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Balint’s Syndrome
Comprises: Ocular apraxia: inability to voluntarily direct one’s gaze to a
particular point (Charles and Hillis, 2005). Results in tendency to fix gaze on a single object
Optic ataxia: impairment of goal-directed hand movements towards visually presented targets (Trillenberg et al., 2007). Results in misreaching for objects
Simultanagnosia: inability to perceive two or more objects simultaneously
Damage to bilateral dorsal occipitoparietal regions
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Gerstmann’s Syndrome
Comprises:1. Acalculia2. Agraphia3. Finger agnosia4. Left-right disorientation
Left inferior parietal damage in region of angular gyrus
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Pathology in PCA
Alzheimer’s pathology predominant Rarely: corticobasal degeneration, dementia with
Lewy Bodies, prion disease Distribution of pathology differs to AD:
High density of neurofibrillary tangles in occipital regions
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Management of PCA
No proven treatment
Consider cholinesterase inhibitors
Important to make diagnosis to stop inappropriate further investigation and/or intervention
Supportive measures – assistance with dressing, reduce reliance on visual cues, alternatives to driving
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Young-Onset Dementia
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Young-Onset Alzheimer’s Disease
Co-existence of cerebrovascular disease, renal and cardiac disease much less common
Autosomal dominant familial AD more common Myoclonus Preserved naming Speech production deficits
Non-amnestic presentation comprised 1/3 of cases (c.f. 5% in older onset) Posterior Cortical Atrophy is most common
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Young-Onset Vascular Dementia
Greater association with vascular risk factors Rarer causes of early cerebrovascular disease
should be considered Cerebral Autosomal Dominant Arteriopathy with
Subcortical Infarcts and Leukoencephalopathy (CADASIL)
Amyloid angiopathy (inflammatory type treatable) Vasculitis
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Young-Onset Frontotemporal Lobar Degeneration (FTLD)
Accounts for greater proportion of dementias in younger compared to later onset
20-40% of FTLD familial in cases referred to specialist centres
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Young-Onset Dementia with Lewy Bodies
Dementia with Lewy Bodies is usually pathologically characterised by Lewy bodies, senile plaques and tangles
Rare younger onset form where only Lewy bodies are present
In younger onset Parkinson’s disease, tend to have dementia less frequently and after longer duration
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Investigations for Young-Onset Dementia
Laboratory investigations FBC, biochemical screens Syphilis and HIV serology Auto-antibodies, antineuronal antibodies
Neurogenetics MRI brain Neurophysiology
EEG, nerve conduction studies, EMG Lumbar puncture
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Young-Onset Dementia
Early, accurate diagnosis Impact on work and ability to continue working Address driving capability
Roads and Traffic Authority Driver Assessment and Rehabilitation Service (ACT Health) Fitness to Drive Medical Clinic (ACT Health)
Enduring Power of Attorney and Advanced Care Directive Assistance at home and respite services
Disability ACT, National Disability Insurance Scheme (≤65 years) Aged Care Assessment Team (>65 years)
Companion card, Taxi Subsidy
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Reference
Rossor MN, Fox NC, Mummery CJ, Schott JM, Warren JD. The Diagnosis of Young-Onset Dementia. Lancet Neurology 2010; 9 (8): 793-806
Beh SC, Muthusamy B, Calabresi P, et al. Hiding in plain sight: a closer look at posterior cortical atrophy. Practical Neurology 2014;0:1–9