Vascular dementia; Alzheimers Flashcards
Describe what is meant by vascular dementia [1]
Dementia caused by vascular brain injury or dysfunction as a result of conditions that impair cerebral blood flow including chronic small vessel disease, stroke or haemorrhage.
Vascular cognitive impairment (VCI) refers to a syndrome of all cognitive disorders which are due to cerebrovascular disease. VD is considered the most severe form of VCI
Any condition that affects the brain parenchyma by impairing cerebral blood flow (i.e. ischaemia) or causing haemorrhage can lead to vascular cognitive impairment, and therefore, VD. Causes include: [4]
Ischaemic stroke:
- any cause (e.g. atrial fibrillation with emboli, carotid artery disease)
Small vessel disease:
- atherosclerosis due to traditional cardiovascular risk factors (hypertension, diabetes, hypercholesterolaemia, smoking)
Haemorrhage
- intracerebral, subarachnoid
Other:
- cerebral amyloid, which is a cause of small vessel disease. Deposition of amyloid in small arteries.
This is an autosomal dominant inherited condition termed ‘cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy’.
It is due to mutation in the [] gene and leads to arterial thickening and occlusion.
This is an autosomal dominant inherited condition termed ‘cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy’.
It is due to mutation in the NOTCH3 gene and leads to arterial thickening and occlusion.
Vascular cognitive impairment (VCI) refers to a syndrome of all cognitive disorders which are due to cerebrovascular disease. VD is considered the most severe form of VCI
The main forms of VD are: [4]
Subcortical VD:
- Dementia caused by disease affecting the small vessels of the brain which predominantly supply the subcortical white matter.
Stroke-related VD:
- Development of dementia following a large cortical stroke. Up to 20% develop this within the next 6 months.
Single or multi-infarct VD:
- Development of dementia following a single, or multiple small strokes. It is the collective burden of cerebrovascular disease from these strokes that precipitates development of dementia.
Mixed dementia:
- Features of more than one type of dementia (usually VD and AD). For example, a patient may have significant cardiovascular risk factors and previous strokes but cognitive defects highly suspicious of AD. Based on neuropathological assessment, pure VD is less common than expected.
Describe the clinical features of VD
Several months or several years of a history of a sudden or stepwise deterioration of cognitive function.
Symptoms and the speed of progression vary but may include:
* Focal neurological abnormalities e.g. visual disturbance, sensory or motor symptoms
* The difficulty with attention and concentration
* Seizures
* Memory disturbance
* Gait disturbance
* Speech disturbance
* Emotional disturbance
VD: typically a ‘stepwise’ decline in function. Predominant gait, attention and personality changes. May have focal neurological signs (e.g. previous stroke)
Describe how you diagnose VD [3]
National Institute for health and care excellence (NICE) recommends that diagnosis be made using the NINDS-AIREN criteria for probable vascular dementia:
Presence of cognitive decline that interferes with activities of daily living, not due to secondary effects of the cerebrovascular event
Cerebrovascular disease
- defined by neurological signs and/or brain imaging
A relationship between the above two disorders inferred by:
* the onset of dementia within three months following a recognised stroke
* an abrupt deterioration in cognitive functions
* fluctuating, stepwise progression of cognitive deficits
Management for VD? [1]
There is no specific pharmacological treatment approved for cognitive symptoms
Only consider AChE inhibitors or memantine for people with vascular dementia if they have suspected comorbid Alzheimer’s disease, Parkinson’s disease dementia or dementia with Lewy bodies.
A 75-year-old man with a history of hypertension presents with memory problems. His wife reports that he has had a number of sudden deteriorations over the past 2 years but then seems to stay the same - vascular dementia
Which genes are recognised risk factors for AD? [4]
Apolipoprotein E (APOE):
- The APOE gene has three alleles: ε2, ε3, and ε4.
- ε4 allele is associated with an increased risk and earlier onset AD
- ε2 allele appears to have a protective effect.
Mutations in PSEN1; PSEN2 and APP genes increase the liklihood of AD
Which genes are recognised as risk factors for AD?
Describe the pathophysiology of AD
The two key pathological changes in AD are senile / amyloid plaques and neurofibrillary tau tangles
Deposits of beta-amyloid:
- Extracellular
Neurofibrillary tau tangles:
- in AD are tau proteins are excessively phosphorylated, impairing the function
- Intracellular
Brain changes:
- widespread cerebral atrophy, particularly involving the cortex and hippocampus
- biochemical: there is a deficit of acetylcholine from damage to an ascending forebrain projection
Describe the clinical features of AD [+]
Cognitive impairment
* memory loss: generally affects recent events more than distant memories
* difficulty learning new information
* the person may defer to family members when answering questions,
* vague with dates
* problems with reasoning and communication
* difficulty in making decisions/executive function
* nominal dysphasia
* sleep cycle disturbance
Behavioural and psychological symptoms of dementia
these features generally fluctuate
* depression
* agitation
* psychosis
* apathy
* disinhibition
Describe how you investigate for AD
The diagnosis of Alzheimer’s disease (AD) is primarily clinical; however, investigations can help rule out other causes of dementia, aid in confirming an AD diagnosis and contribute to staging the disease.
First-line Investigations:
One: Cognitive Testing:
- Mini-Mental State Examination (MMSE)
- The Montreal Cognitive Assessment (MoCA)
- Addenbrooke’s Cognitive Examination III
Two: Blood tests:
- FBC; UE; LFTs; TFTs; B12 and folate should be check for causes of cognitive impairment
Three: Brain imaging:
- CT or MRI to exclude other cerebral pathologies
2nd line Investigations:
- CSF analysis: beta-amyloid 42 decreased; total tau or P-tau is increased
- Amyloid PET imaging
Describe the pharmocological management for AD
First line: acetylcholinesterase inhibitors:
- donepezil; rivastigmine; galantamine
2nd Line: NMDA receptor antagonist
- memantine
NICE does NOT recommend antidepressants for mild to moderate depression in patients with dementia
NMDA receptor antagonist
acetylcholinesterase inhibitor
