Vascular dementia is the second most common cause of dementia after Alzheimer's disease. This represents a heterogeneous group of cognitive disorders resulting from cerebro vascular pathology. It is characterized by cognitive impairment severe enough to interfere with daily functioning and is often associated with focal neurological deficit and a step wise clinical progress. Early diagnosis is crucial as vascular dementia is preventable and partially modifiable.This review provides an overview of Vascular Dementia, it's definition, classification, clinical features, diagnostic criteria and the role of imaging. In this review I bring out important aspects of genetically mediated dementias which are of early onset and current approach of the diagnosis and management strategies.

Dementia is defined as a decline in mental function from primary high level severe enough to interfere with daily living. There will be two or more specific difficulties of MEMORY, REASONING, LANGUAGE, COORDINATION, MOOD AND BEHAVIOUR.

Vascular dementia is the second most common cause of dementia after Alzheimer's disease. This is because of diminished blood supply to the brain. Mainly classified in to post stroke dementia involving large vessels, Multi infarct dementia and small vessel ischemic changes in sub cortical regions resulting in Binswangers disease.

The incidence comes to about 2.5 to 3.8 per one thousand people per year. There are certain risk factors identified which are responsible for vascular dementia. These are Hypertension, Diabetes Mellitus, Smoking and hyperlipidemia. Control of these risk factors Will prevent the development of this dementia. There are certain dementias of early onset like CADASIL and CARASIL which are genetically mediated are specifically discussed in this review. Various modes of investigations and management strategies are discussed in detail.

Classification:

Dementias are broadly classified into: [4].

Primary Dementias: where these is direct damage to the neurons and it is irreversible these are:

1. Alzheimer's disease
2. VASCULAR dementia
3. Lewvy body dementia
4. Mixed dementia
5. Dementia associated with Parkinson's disease

Secondary Dementias: Dementias arising from some other underlying conditions or external factors. These are sometimes reversible or altered if the underlying causes are treated.

Such conditions are:

1. Normal pressure hydrocephalus
2. Subdural haematomas
3. Infections
4. Metabolic and endocrine disorders like Addison's disease and Cushing syndrome
5. Heavy metal toxicity
6. Brain tumors
7. Drug induced cognitive impairment
8. Traumatic brain injury
9. Vitamin deficiencies like B1, B6, ANDB12
10. Alcohol abuse

Identifications of reversible dementias is critical as timely treatment will significantly improve the cognitive function.

Vascular Dementia

This is the second most common cause of primay dementias second to Alzheimer's Dementia.

Types Of Vascular Dementias [2].

1. POST STROKE DEMENTIA
2. MULTI INFARCT DEMENTIA
3. BINSWANGERS DISEASE
4. MIXED DEMENTIA

Pathophysiology:

Vascular Dementia may be because of ischemic stroke or haemorrhagic stroke. The main pathology lies in the VASCULAR damage because of atheromatous change in the vessel wall. May be large vessels involvement involving large area of brain or sometimes the intracerebral haemorrhage producing post stroke dementia. It may be because of involvement of multiple vessels involving multiple strategic areas of brain producing Multi infarct dementia.

Sometimes small vessel involvement producing micro vascular ischemic changes producing so called Binswangers disease.

It's not rare to come across amyloid angiopathy which may be responsible for lobar haematomas and Dementia.

One moreimportant cause of Vascular Dementia is Thromboembolic manifestation of cardiac origin which is responsible for Multi infarct Dementia.

If we take the early onset dementia in to consideration CADASIL AND CARASIL will come into the picture.

The main etiology in CADASIL is genetic mediation such as NOTCH 3 Gene which is responsible for the maintenance of the integrity of the vascular endothelium. The mutation in this gene produces recurrent strokes in young individuals.

Coming to CARASIL it's because of the mutation in HTRA 1 gene which is responsible for dementia from childhood itself and is progressive.

Symptoms Of   Vascular Dementias [2].

Confusion, sleeping issues, Memory loss. Trouble in understanding and using words. Personality and behavioural changes.

Urinary Incontinence, Trouble in concentration

Emotional incontinence and Dawn phenomenon where the patient feels worse in the evening and night.

Step wise progression of the symptoms is an important manifestation. These are the common manifestations with which these patients present.

Stages Of Dementia [3].

1.             Early stage where there is mild cognitive change and memory disturbances

2.             Middle stage where there is increased confusion, worsening of memory loss and difficulty in performing daily activities.

3.             Late stage: sever cognitive impairment, loss of physical abilities and dependence on daily care.

Diagnosis:

Clinical: Diagnosis of Vascular Dementia is primarily clinical and supported by neuroimaging and in rare circumstances genetic analysis.

A key diagnostic tool is the HACHINSKI ISCHEMIC SCORE with a total score of 18.

Score less than 4 indicates Alzheimer's Dementia. Score more than 7 suggests Vascular Dementia.

Major components carrying two points each include:

Abrupt onset Fluctuating course History of stroke

Focal neurological symptoms Focal neurological signs

Additional features such as hypertension, depression, emotional incontinence, personality changes, atherosclerosis, and somatic complaints, Nocturnal confusion, and step wise determination carry one point each which further aid in the diagnosis.

Imaging: CT scan and MRI brain confirms recent Stroke involving large vessel, Multiple infafrcts involving different strategic areas responsible for Multi infarct dementia. In addition, small vessel ischemic changes in the subcortical regions in Binswangers disease. MRI Plays a great role in identifying the various types of vascular dementia.

PET CT is one important investigation in identifying other dementias. CSF Analysis is a useful tool in the diagnosis of other primary dementias.

Genetic Analysis: This is useful in the diagnosis of CADASIL (CEREBRAL AUTOSOMAL DOMINANT ARTERIOPATHY WITH SUBCORTICAL ISCHEMIC LEUKOENCEPHALOPATHY) Where we find mutation in NOTCH 3 Gene and CARASIL (CEREBRAL AUTOSOMAL RECESSIVE ARTERIOPATHY WITH SUBCORTICAL ISCHEMIC

LEUKOENCEPHALOPATHY) where we find mutation in HTRA 1 gene.

Causes of Dementia:

Age after 60 yrs Atrial fibrillation

Diabetes Mellitus, Hypertension Hyperlipidemia, Smoking History of stroke

Narrowing of blood vessels and capillaries in the brain. Haemorrhages [5].

Diagnostic criteria:

• Neuro cognitive testing to confirm MCI or Dementia
• Brain imaging: To confirm recent Stroke or other vascular brain changes To rule out other factors which contribute to cognitive impairment.

Diagnostic tests:

• CSF: For auto immune conditions or other neuro degenerative conditions
• Brain Imaging: CT SCAN and MRI BRAIN To identify strokes, Haemorrhages or tumours
• Clinical Diagnosis: USING HACHINSKI score gives good aid in the diagnosis of Vascular Dementia.

Binswangers Disease [2].

A type of vascular cognitive impairment

Extensive white matter hyper intensities with gradual subcortical ischemia

Patients develop neurological findings like cognitive impairment and gait disturbances.

Clinical features:

Cognitive impairment

Slowed processing speed and executive functioning are most affected. Pyramidal and Extra pyramidal signs and ataxia are associated.

Which are all progressive

Imaging features:

• White matter hyper intensities in T2 more than 25 %.
• Brain atrophy mild to moderate
• Lacunar infafrcts and micro bleeds
• Enlarged peri ventricular spaces
• Intracranial atherosclerosis

Differential diagnosis:

• Amyloid angiopathy, CNS vasculitis
• CADASIL AND CARASIL
• Late onset M S
• Adult Leukodystrophy
• Border zone strokes and
• NPH (Normal pressure hydrocephalus)

The role of imaging:

• MRI Sequences play useful role in the diagnosis
• White matter hyper intensities subcortical both peri ventricular and deep are associated.
• Lacunar strokes are extremely frequent.
• Enlarged peri ventricular spaces, micro bleeds, Atherosclerosis with dolichectasis of intra cerebral vessels is common.

Other ancillary studies:

• CSF Albumin index and increase in MMP9
• Normal or decreased levels of amyloid BETA 1-42
• Transcranial Doppler
• Perfusion imaging of white matter shows decreased blood flow in white matter.
• Spectroscopy of white matter shows decreased NAA and creatinin.             

Treatment:

Control of blood pressure

Antiplatelet therapy with Aspirin and Statins

Continued physical activities prevent cognitive impairment. Rehabilitation is useful.

Acetyl choline receptor antagonists like Donepezil and NMDA antagonists like Memantine are useful in preventing the progress of the disease.

Anticoagulants are useful in some cardiac diseases.

Cadasil Dementia: (Cerebral Autosomal dominant arteriopathy with subcortical ischemic leukoencephalopathy) [8].

It is a hereditary form of vascular dementia

Pathogenesis: Mutation in NOTCH 3 Gene is responsible in resulting in thickening of small vessels. This Gene is responsible for maintaining integrity ofthe vascular endothelium the absence of which will produce the abnormality and blockage of small vessels. This results in recurrent strokes, lacunar infafrcts and Leukoencephathy.

Small areas of bleeding may be there.

There is a progressive decline in mental function.

Symptoms: Migraine with Aura

Strokes from childhood to late adult hood.

Progressive decline in thinking and executive functioning Mood and behavioural changes are seen.

Gait disturbances and bladder incontinence are common manifestations. Pseudo bulbar palsy, seizures and visual problems are seen.

Parkinsonism is an important assosiation and aids as clue in the diagnosis. Vertigo and abnormal gait are the associated findings.

Treatment: There is no cure Needs symptomatic treatment.

Prevent further strokes by controlling vascular risk factors.

Life style modification is needed for leading near normal life as far as possible. Diagnosis: Blood test and skin biopsy for NOTCH 3 Gene.

Carasil: (Cerebral autosomal recessive arteriopathy with subcortical ischemic leukoencephalopathy) [8].

It is a rare hereditary small vessel disease leading to vascular dementia.

Symptoms: Starts in early to mid-child hood. Progressive dementia.

Premature hair loss and low back ache are common association.

Muscle spasticity and gait disturbances are associated. Mood changes are very common. PATHOLOGY: Genetic mutation in HTRA 1 gene is responsible for the changes in the vessel wall and blockage resulting in progressive damage in brain.

Treatment: No cure.

Supportive and symptomatic treatment is needed

Treatment of Spasticity and prevention of further strokes prevent further deterioration.

Management of vascular dementias:

Pharmocologic treatment:

• Management of comorbid conditions like
• Control of Hypertension, Diabetes Mellitus and Hyperlipidemia.
• Antiplatelet therapy Where ever it's indicated.

Non pharmocologic treatment:

• Cognitive rehabilitation
• Physical activities.
• Life style modification

Prognosis:

Depends on the amount of vascular damage and the areas of involvement of the brain Effective control of risk factors

Prevention remains the corner stone in the management of vascular dementia.

Dementia is defined as decline in mental function from primary high level severe enough to interfere with Norma daily living. They will have two or more specific difficulties of memory, reasoning, language, coordination, mood and behaviour.

VASCULAR dementia is the second most common cause of dementia after Alzheimer's disease. Most of the times it's because of diminished blood supply to the brain and rarely Intracerebral haemorrhages.

Dementias are mainly devided in to primary and secondary Dementias.

Secondary Dementias are because of external factors responsible for the destruction of the neurons and removal or control of the responsible factors improves the dementia, where as in the primary dementias there is direct damage or neuro degeneration and are often irreversible.

Most of the primary dementias are either treatable or preventable such as vascular dementia. None of them are curable.

Vascular Dementias Are Classified Into: [1].

1. Post stroke dementia where large vessel involvement producing damage to larger area of brain
2. Multi infarct dementia where multiple infarcts in different areas of brain is responsible for the dementia.
3. Small vessel ischemic changes or Binswangers disease resulting in micro vascular ischemic encephalopathy and sub cortical dementia where the connecting system in the brain is damaged producing Binswangers disease.
4. Mixed dementia where Vascular Dementia is associated with Alzheimer's disease

There are certain risk factors which are responsible for these dementias. These are mainly Hyper tension, Diabetes Mellitus, Hyper lipidaemia, Smoking,and Alcoholism.

Apart from these dementias there are certain

5.             Genetic dementias like CADASIL [8], and CARASIL which are genetically mediated and the responsible genes being NOTCH 3 GENE Mutation in the former and HTRA 1 gene mutation in the later. These genetically mediated dementias occur in the early age group with different clinical manifestations and

6.             One more addition of cysteine C Amyloid angiopathy [6], where in the patients have recurrent cerebral haemorrhages before the age of 40 yrs which lead to dementia.

All the vascular dementias can be diagnosed by clinical examination using Hackinschi score, imaging like CT SCAN and more appropriately MRI BRAIN and MRI diffusion abnormality in Binswangers disease. Genetic analysis aids in the diagnosis of the above two genetic dementias.

Various clinical manifestations of different types of vascular dementias have been discussed in detail previously. The important clinical differentiation between Vascular Dementia and other dementias is there is delayed thinking and reasoning rather than memory impairment in vascular dementias.

Laboratory evaluation for haematological abnormalities can identify the Hyper lipidaemia, and hyper glycemia. Cardiac evaluation by 2D ECHO gives a clue for the cardio embolic strokes. Neck vessel Doppler and Neck and brain 4 vessel angio aids in identifying the vascular risk factors.

The risk factor identification gives the clinician the idea of prevention of further progression of Dementia.

When once the diagnosis is made and risk factors are identified the Dementia can be prevented from further progress and disability.

The management strstegies include:

Risk factor manegement like:

Control of Hypertension Control of Diabetes Mellitus Avoid Smoking and Alcohol Treatment of Hyper lipidaemia

Life style modification and rehabilitation.

Medical management:

Acetyl choline receptor antagonists like Donepezil and

NMDA RECEPTOR antagonist like Mimantine are useful for prevention of further progress of the dementia.

Antiplatelets in ischemic strokes and anti-coagulants in some cardio embolic strokes are highly useful in preventing further progress of the disease.

Symptomatic management of some of the symptoms in genetic dementias is useful.
 

Post Stroke Dementia                              Multi Infarct Dementia.                             Binswangers Dementia

Take home message:

VASCULAR dementias are treatable and preventable

Diagnosis can be done by clinical examination using Hackinschi score and using CT scan brain and MRI BRAIN along with haematological and cardiac evaluation.

Risk factor identification makes the clinician to prevent further progress of the dementia. A note should be made of genetic analysis to identify genetically mediated dementias.