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Generalized Neurodegenerative
dementias
AD
Dementia with Lewy Bodies (DLB)
Mixed
Frontotemporal Lobar Degeneration
(FTLD)
Others
DLB: Clinical
Features
1. Cognitive decline
2. Visual hallucinations
3. Parkinsonism
4. Adverse reactions to neuroleptics
6. Falls / syncope / transient loss of consciousness
5. Other psychotic features
DLB: Cognitive
Aspects
• Similar decline rate as in AD, leading to global
dementia
• Fluctuations of attention
• Deficits of executive function, visuospatial
ability and verbal fluency might be more
prominent than memory deficits
DLB: Visual
Hallucinations
• Recurrent, commonly involving animated
figures that might form part of the patient’s
‘daily routine’ and familiar surroundings
• Patient has insight
• Reactions vary, most commonly patients are not
threatened by the hallucinations
DLB: Parkinsonism
• Appears around the same time as the other
clinical features
• Bradykinesia and rigidity are prominent
• Tremor might be mild
• Hypophonic speech
DLB: Neuroleptics Sensitivity
• Severe rigid-akinetic side-effects
• Neuroleptic malignant syndrome
DLB: Other Psychotic/
Psychiatric Features
• Other types of hallucinations
(auditive/mixed)
• Delusions
• Depressive symptoms
DLB
• Falls: May be secondary to Parkinsonism
• Syncope/Transient loss of consciousness:
Might be related to brainstem and
autonomic nervous system involvement
DLB: Prevalence
• Varies 15 - 36% of demented patients at
autopsy
DLB: Differential Diagnosis
1. AD / Vascular / Mixed Dementias
2. Parkinson’s Disease with dementia
3. Parkinson’s plus syndromes
DLB: Management (1)
Investigations
• There is no specific test for the diagnosis of DLB.
Clinical history is the best available tool.
• Rule out reversible / other causes of dementia
(standard blood work, imaging)
• Cognitive test / physical exam
• Ask patient and family about presence of
hallucinations
DLB: Management (2)
Treatment
• Acetylcholinesterase inhibitors (Aricept, Exelon,
Reminyl)
• Dopaminergic drugs
• Most patients do not require treatment for the
hallucinations. If they do, small does of atypical
neuroleptics might be used (Risperdal)
• SSRI’s for depression
Vascular and Mixed
Dementias
Vascular Dementia
(VaD)
• Accounts for about 20% of cases of dementia
• Another 20% of cases are a combination of AD
and vascular causes
• Usually affects people between 60 and 75 years
old
• Slightly more common in men
Source: The “Dementia”Directory. Vascular Dementia.
Available at http://www.zarcrom.com/users/alzheimers/odem/d4.html.
Relationship among AD,
VaD and other dementias
VaD
AD
Other
Cras, 1998
Vascular dementia
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Abrupt onset and stepwise progression
Might involve small, large or any vessel/s
History of stroke/s.
Hypertension, diabetes and elevated
Homocysteine are strong risk factors.
• Cognitive abnormalities depending on the areas
affected
• “Sub-cortical” symptoms (slow processing,
depression, emotional incontinence, somatic
complaints)
• Hachinski Ischemic Score (HIS) vs ADDTC
criteria
Hachinski Ischemic score
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Abrupt onset
Stepwise deterioration
Fluctuating course
Nocturnal confusion
Preservation of personality
Depression
Somatic complains
Emotional incontinence
History of hypertension
History of stroke
Associated atherosclerosis
Focal neurological symptoms
Focal neurological signs
Associated atherosclerosis
Focal neurological symptoms
Focal neurological signs
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Sub-types of Vascular
Dementia
• Cortical vascular dementia or multi-infract dementia
– Large vessel disease
– Cardiac embolic events
 Subcortical vascular dementia or small vessel dementia
– Small vessel disease
• Strategic infract dementia
– Large vessel disease
– Cardiac embolic events
– Small vessel disease
Source: Alzheimer’s Disease and related Disorders Annual.
2000 Editors: Gauthier S., Cummings JL.
Treatments of Vascular dementia
– Prevention of further strokes, consider:
• Anticoagulation if Atrial Fibrillation
• ECASA
• Control of blood pressure
• Diabetes control
• Lipids control
Mixed dementia
• Symptoms of both neurodegenerative and
vascular dementia
• Presence of “microangiopathic” disease,
White matter disease
• Same risk factors as for neurodegenerative
and vascular dementia.
• Imaging: Atrophy, lacunar infarcts and
white matter disease
Treatment mixed dementia
Acetylcholinesterase inhibitors
and
Stroke prevention
Focal neurodegenerative
dementias: Frontotemporal Lobar
Degeneration (FTLD)
Focal neurodegenerative diseases, affecting
primarily temporal and frontal lobes:
1. Fronto-temporal dementia
2. Primary progressive aphasia
3. Semantic dementia
FTLD - General Features
1. Pre-senile dementias (<65 years of age)
2. SPECT Scan: Anterior (frontotemporal defects)
3. Normal EEG
4. Memory and visuospatial functions are normal
until the disease is advanced
FTD: Pathological Types
• Pick’s disease
• Non-specific frontal degeneration
• Frontal degeneration with anterior spinal neuron
loss
FTD: Clinical Features (I)
• Behavioral abnormalities.
• Inertia, loss of volition, decreased
initiative.
• Social disinhibition, loss of insight.
• Impulsivity, overactivity.
• Emotional blunting.
• Stereotyped and perseverative behavior.
FTD: Clinical Features (II)
• Mean age of presentation: 53 years
• Predominantly males
• High familial aggregation
FTD: Clinical Features (III)
• Cognitive impairment mostly in areas of
executive function (planning, judgement,
problem-solving) and attention
• Memory, visuospatial and calculation might be
relatively preserved at the beginning
• Speech might be either economical leading to
mutism, or increased / pressed in disinhibited
patients
FTD: Treatment /
Management
• No effective treatment available
• SSRI’s/Dopaminergic Drugs
• Neuroleptics
• Genetic Studies (CH 17)
PPA
• Gradual and progressive non-fluent aphasia
during a period of 5 - 10 years leading to
dissolution of language function
• Prominence of phonemic errors
PPA
• Memory, visuospatial, reasoning, insight,
judgement and behaviour remain normal
for years
• IADL’s and ADL’s remain normal for
years, and patients can learn new things
such as sign language
PPA
• Difficulties with single word repetition
• Writing is preserved early in the disease, but is
lost later
• Language comprehension is also lost later in the
disease
PPA Management
• No effective treatment available
• Learning of alternative communication skills
SD: Core Features
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Fluent, empty spontaneous speech
Loss of meaning of words
Semantic paraphasias
Prosopagnosia/associative agnosia
Preserved single word repetition and
ability to read aloud and write to dictation
SD: Supportive Features
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Press of speech
Idiosyncratic word usage
Absence of phonemic paraphasias
Preserved calculation
Behavioural changes
- loss of empathy
- narrowed interests
- abnormal preoccupation with money
SD
• Memory and visuospatial are preserved
• Orientation is normal
Other dementias
1. Associated with Parkinson’s disease:
Motor symptoms of Parkinson’s disease
predates cognitive dysfunction by years.
Most commonly appears in advanced
Parkinson’s patients.
“Sub-cortical” features: prominent mood
abnormalities, apraxia, memory might be
preserved.
2. Normal Pressure Hydrocephalus (NPH)
• Isolated cognitive deficits
• Gait abnormality (apraxic gait)
• Incontinence
• Prominent large ventricles with minimal
cortical atrophy
• Surgical treatment
3. Metabolic disease
A. Cobalamin (B12), Folate deficiencies
Causing or contributing to dementia?
15-30% of seniors have B12 deficiency
May cause white matter disease
(demyelination)
Most patients with dementia and B12
deficiency don’t improve after B12 therapy
B. Hypothyroidism
May contribute to cognitive deficits in adults
Severe cognitive deficits in children
• 4. Creutzfeldt-Jakob
– Spongiform encephalopathies.
– Prion disease
– Rapidly progressing dementia causing death
within weeks or months of onset.
– Initial symptoms might be cerebellar with
ataxia, dysarthria and coordination defects.
– Animal/blood transmission
– Diagnosis: 14-3-3 brain protein
Treatment of other dementias
• No available treatment for dementia
associated with Parkinson’s disease,
Parkinson’s plus syndromes, alcoholic
dementia or infectious dementias.
• Surgical treatment for NPH. Refer to
neurosurgery. Possible post-surgical
cognitive improvement and stop
progression of the disease.
Care of the patients with
dementia (I)
• Inform and teach the family and caregivers about
the nature and progression of the disease.
• Refer to Alzheimer’s society
• Driving
• Power of attorney
• Respite and home care programs. Future plans
• Genetic testing?
Care of the patient with dementia
(II)
• Maintain high level of activity (exercise
programs, daily activities).
• Nutrition. Check for weight loss and
nutritional indices (B12, albumin)
• Encourage personal and social functions as
much as possible
Common problems in patients
with dementia (1)
• 1. DELIRIUM: Defined as fluctuating
impairment of attention and orientation,
usually of acute onset and due to a medical
condition. Reversible
50% of patients with delirium have
underlying dementia
Presence of delirium precludes cognitive
testing for dementia
Common problems in patients
with dementia (2)
• 2. NUTRITION: Most patients with dementia
have some degree of malnutrition, which is worse
as the disease advances. Use of nutritional
supplements and multivitamins is recommended.
• 3. INCONTINENCE: Usually a late
manifestation. Many drugs used for treatment of
incontinence will worsen cognition.
• 4. SLEEP DISTURBANCE: Very common,
avoid medications as much as possible.
Other dementias
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Parkinson’s disease
B12 deficiency – Metabolic
Normal pressure hydrocephalus
Parkinson’s plus syndromes (Multiple
systems atrophy or MSA, Progressive
supranuclear palsy or PSP)
• Infectious: Creutzfeldt-Jakob, HIV, Syphilis
• Alcohol related
Prognosis
• Poor at present:
– Most patients suffer progression of the disease
manifested first by increased dependence on
caregivers, and latter by loss of capacity to
perform basic activities of daily living.
– Patients with advanced dementia will suffer
incontinence, motor abnormalities and finally
death.
Future perspectives
• Current clinical trials on vaccines:
– APP
– Promising results on animal experimentation
• Neuro-regeneration drugs:
– Nerve-growth factor
• Better understanding of environmental and genetic
factors that might contribute or trigger the disease.
• Further development of “symptomatic” drugs