Dementia
is defined as a syndrome consisting of chronic, acquired, generalized and
progressive impairment in two or more areas of cognition (i.e., memory,
speech, problem-solving, praxis, gnosis, Visuospatial orientation,
personality and behavior) sufficient to interfere with social activities,
relationships and work, in the absence of impairment of arousal .
Mild cognitive impairment:
a syndrome consider to be a transient state
between normal cognitive function and dementia.
Common complaints are difficulty remembering names and appointments
or solving complex problems. Their memory is worse than age-matched
controls.
Epidemiology
Dementia is, predominantly, a disorder of later life.
The prevalence increase with advancing age
Ages 40-65
1 in 1000
Ages 65-70
2%
Ages 70-80
5%
Age 80+
>20%
Causes
A very large number of neurological diseases can cause dementia, but
most of these are very rare. Alzheimer's disease is by far the most
common cause of dementia, comprising between 60 and 80 per cent of
cases.
Vascular dementia remains the second most common cause, accounting
for 10 to 20 per cent of cases
.
The term vascular dementia encompasses a
number of separate disorders, the most common being multi-infarct
disease.
Of the inherited disorders that may present as dementia, Huntington's
disease is the most common.
Primary infection of the central nervous system by human
immunodeficiency virus is now the most common cause of early-onset
dementia in some parts of the world. The AIDS-dementia complex, which
develops early in the course of the disease, may be the sole manifestation.
Unfortunately, curable disease still accounts for only a small minority of cases.
Rapid onset and rapid progression dementia shift the attention to etiologies
other than degenerative which include: vascular, inflammatory, metabolic,
toxic, neoplastic and infectious.
CAUSES OF DEMINTIA
1-
Inherited
Alzheimer’s disease ,Fronto-temporal dementia
Leukodystrophies
,Huntington’s
disease ,Wilson’s disease
,Dystrophia myotonica ,Lewy body dementia ,Progressive
supranuclear palsy ,Mitochondrial encephalopathies ,Cortico-basal
degeneration
2-
Vascular
Diffuse small-vessel disease ,Amyloid angiopathy
,Multiple
emboli
,Cerebral
vasculitis
,Systemic
lupus
erythematosus
3-
Neoplastic
Secondary deposits, Primary cerebral tumour
,Paraneoplastic syndrome (limbic encephalitis)
4-
Inflammatory
– Multiple sclerosis Sarcoidosis
5-
Traumatic
Chronic subdural haematoma ,Post-head injury
,Punch-drunk syndrome.
6-
Hydrocephalus
Communicating/non-communicating
,‘normal
pressure’ hydrocephalus
7-
Toxic/nutritional
Alcohol, Thiamin deficiency, Vitamin B12
deficiency ,Anoxia/carbon monoxide poisoning, Heavy metal
poisoning .
8-
Infective
– Syphilis ,HIV, Post-encephalitis ,Whipple’s disease
,Subacute sclerosing panencephalitis
9-
Prion diseases
Sporadic Creutzfeldt–Jakob disease (CJD) ,Variant
CJD ,Kuru ,Gerstmann–Strنussler–Scheinker disease
Reversible causes of dementia
1
.
Subdural hematoma. This treatable complication of head injury can
present with dementia, often associated with symptoms of raised
intracranial pressure.
2. Normal pressure hydrocephalus. The classical presentation of
normal-pressure hydrocephalus is a triad of cognitive impairment, gait
disturbance, and incontinence.
3. B12 deficiency
4. Hypothyroidism
5. Infection, e.g., syphilis, HIV
6. Benign tumors
Classification
Early attempt to classify dementia distinguished between senile and
presenile dementia. This proved unhelpful, since the same pathological
processes can afflict the elderly and the relatively young.
The terms cortical and subcortical dementia is used to distinguish
between two variants of dementia syndrome. The term does not imply
that pathological changes are limited to cortical or subcortical structures.
The division between those diseases that affect primarily the cerebral
cortex and those that have their major pathological impact on subcortical
structures (i.e., the basal ganglia, thalamus, and deep white matter) has
proved useful.
Characteristic features of subcortical dementia
1. Planning, organizing, prioritizing, problem-solving, initiation
disproportionately impaired from onset
2. Speed of cognitive processing slowed down
3. Emotional flatness, loss of motivation.
4. Memory impairment present mildly initially
Vascular dementia, Huntington’s disease and AIDS-dementia complex
Characteristic features of cortical dementia
1. Severe amnesia
2. Aphasia
3. Apraxia
4. Visuospatial disorientation
5. Personality typically apathetic and inert.
6. Social withdrawal
7. Disinhibition
Alzheimer's disease, Normal-pressure hydrocephalus and Creutzfeldt-
Jakob disease.
Assessment of suspected dementia
There are two questions to be asked when assessing patients with
suspected dementia.
First, does the patient fulfill the criteria for a diagnosis of dementia?
Secondly, if so, what is the likely cause of the dementia?
Investigation in demintia
In most patients
•
Imaging of head (computed tomography and/or magnetic resonance
imaging)
•
Blood tests: Full blood count, erythrocyte sedimentation rate Urea and
electrolytes, glucose Calcium, liver function tests Thyroid function tests
Vitamin B12 Syphilis serology ANA, anti-dsDNA
•
Chest X-ray
•
Electroencephalography
In selected patients
•
Lumbar puncture
•
HIV serology
•
Brain biopsy
Management
This is mainly directed at addressing treatable causes and providing
support for patients and carers. Tackling risk factors may slow
deterioration, e.g. effective management of hypertension in vascular
dementia, or abstinence and vitamin replacement in toxic/nutritional
dementias.
Psychotropic drugs may have a role in alleviating symptoms, such as
disturbance of sleep, perception or mood, but should be used with care
because of an increased mortality in patients who have been treated long-
term with these agents.
If the diagnosis is Alzheimer-type dementia, cholinesterase inhibitors
and memantine may slow progression for a time.
Alzheimer’s disease
Alzheimer disease (AD) is a neurodegenerative disorder featuring
gradually progressive cognitive and functional deficits as well as
behavioral changes and is associated with accumulation of amyloid and
tau depositions in the brain.
Cognitive symptoms of AD most commonly include deficits in short-term
memory, executive and visuospatial dysfunction, and praxis.
Alzheimer’s disease is the most common form of dementia. It increases in
prevalence with age and is rare in people under 45 years. AD is the sixth
most common cause of death
Pathogenesis
Genetic factors play an important role and about 15% of cases are
familial. These cases fall into two main groups:
1. early-onset disease with autosomal dominant inheritance and a
2. later-onset group where the inheritance is polygenic.
The brain in Alzheimer’s disease is macroscopically atrophic, particularly
the cerebral cortex and hippocampus. Histologically, the disease is
characterised by the presence of senile plaques and neurofibrillary tangles
in the cerebral cortex.
In particular, there is impairment of cholinergic transmission, although
abnormalities of noradrenaline (norepinephrine), 5-HT, glutamate and
substance P have also been described.
Clinical features
The key clinical feature is impairment of the ability to remember new
information. Hence, patients present with gradual impairment of memory,
usually in association with disorders of other cortical functions. Short-
and long-term memory are both affected but defects in the former are
usually more obvious. Later in the course of the disease, typical features
include apraxia, visuo-spatial impairment and aphasia.
Depression is commonly present. Occasionally, patients become
aggressive, and the clinical features can be made acutely worse by
intercurrent physical disease.
Patients typically present with subjective memory loss, sometimes getting
lost in familiar locations. A history of progressive memory loss and
associated functional impairment, corroborated by an informant, is the
key to making the diagnosis. Cognitive testing and neuroimaging can be
helpful but in themselves are not diagnostic.
Investigations
Investigation is aimed at excluding treatable causes of dementia as
histological confirmation of the diagnosis usually occurs only after death.
Management
Treatment with anticholinesterases, such as donepezil, rivastigmine and
galantamine, has been shown to be of some benefit at slowing
progression of cognitive impairment in the early stages of the disease
while post-synaptic cholinergic receptors are still available. The N-
methyl-D-aspartate (NMDA) receptor antagonist memantine slightly
enhances learning and memory in early disease and can also be useful in
selected patients with more advanced disease.
Fronto-temporal dementia
Frontotemporal dementia (FTD) classically affects adults in their
fifties to sixties, although cases have been reported in patients from
30 to more than 90 years of age.
FTD is a progressive neurodegenerative disorder; thus, the
patient’s history typically reveals a gradual onset and progression
of changes in behavior or language deficits for several years prior
to presentation .
The term FTD is typically used to refer to one of several clinical
subtypes including
1. behavioral variant of FTD (bvFTD),
2. Semantic variant primary progressive aphasia (PPA),
3. nonfluent agrammatic variant PPA,
4. and FTD associated with motor neuron disease (FTD-MND).
5. FTD-related
disorders
include
two
tau-associated
neurodegenerative diseases,corticobasal syndrome (CBS) and
progressive supranuclear palsy (PSP), which can present with
frontal lobe dysfunction.
The clinical subtypes of FTD and related disorders are defined by
the hallmark patterns of symptoms and signs observed.
In contrast to Alzheimer’s disease, memory is relatively preserved in the
early stages. There is no specific treatment. Disinhibition and compulsive
behaviours can be helped by selective serotonin re-uptake inhibitors
(SSRIs).
Although Alzheimer’s and fronto-temporal dementia share certain
symptoms, they cannot be treated with the same pharmacological agents
because the cholinergic systems are not affected in the latter.
Lewy body dementia
This neurodegenerative disorder is clinically characterised by dementia
and signs of Parkinson’s disease. It is often inherited and mutations in the
α-synuclein and β-synuclein genes have been identified in affected
patients. These mutations result in accumulation of abnormal protein
aggregates in neurons that contain the protein α-synuclein in association
with other proteins, including ubiquitin.
The cognitive state
often fluctuates and there is a high incidence of visual hallucinations.
Affected individuals are particularly sensitive to the side-effects of anti-
parkinsonian medication and also to antipsychotic drugs. There is no
curative treatment but anticholinesterase drugs can be helpful in slowing
progression of cognitive impairment.