Generalized Neurodegenerative dementias

ADDementia with Lewy Bodies (DLB)MixedFrontotemporal 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

Source: The “Dementia”Directory. Vascular Dementia. Available at http://www.zarcrom.com/users/alzheimers/odem/d4.html.

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

Relationship among AD,VaD and other dementias

AD

VaD

Other

Cras, 1998

Vascular dementia

• 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• Abrupt onset 2• Stepwise deterioration 1• Fluctuating course 2• Nocturnal confusion 1• Preservation of personality 1• Depression 1• Somatic complains 1• Emotional incontinence 1• History of hypertension 1• History of stroke 2• Associated atherosclerosis 1• Focal neurological symptoms 2• Focal neurological signs 1• Associated atherosclerosis 1• Focal neurological symptoms 2• Focal neurological signs 1

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

• 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

• 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 diseaseA. Cobalamin (B12), Folate deficiencies

Causing or contributing to dementia?15-30% of seniors have B12 deficiencyMay cause white matter disease

(demyelination)Most patients with dementia and B12

deficiency don’t improve after B12 therapyB. 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

• 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