Cognitive Disorders Flashcards
What is AD?
-Neurodegenerative disorder- neuronal degeneration and loss
-Incidence age-related (exponential)- 0.5% per year in 65-70 age group, 8% per year above 85
-Progressive, typically over years (live 3-11 years after diagnosis)
Describe AD pathophysiology and investigation
-MMSE
=Impaired recall
=Nominal dysphagia
=Disorientation
-Association with abnormally folded protein in CSF
=Abeta: senile plaques
=Tau: neurofibrillary tangles
-MRI: generalised widespread cerebral atrophy with medial temporal lobe and parietal predominance (cortex and hippocampus)
-Beginning in specific neuronal functional areas
=Typically beginning in Medial Temporal Lobes
=Typically Anterograde Episodic Memory Loss
Causes and risk factors of AD
-Some cases Genetic (familial AD)
=Genetic factors involved in non-familial cases
-Age
-Vascular Risk Factors
-Low educational attainment
increasing age
family history of Alzheimer’s disease
5% of cases are inherited as an autosomal dominant trait
mutations in the amyloid precursor protein (chromosome 21), presenilin 1 (chromosome 14) and presenilin 2 (chromosome 1) genes are thought to cause the inherited form
apoprotein E allele E4 - encodes a cholesterol transport protein
Caucasian ethnicity
Down’s syndrome
Symptoms and signs of AD
-Begins with memory problems: loss of episodic memory including recent events, repeated questioning, difficulty learning new information
-Visuo-spatial, language problems develop (nominal dysphasia)
-Personality/ social function often relatively persevered in early stages
=Apathy
=Mood changes
=Difficulty with executive function
Management of AD
Non-pharmacological management
NICE recommend offering ‘a range of activities to promote wellbeing that are tailored to the person’s preference’
NICE recommend offering group cognitive stimulation therapy for patients with mild and moderate dementia
other options to consider include group reminiscence therapy and cognitive rehabilitation
Pharmacological management
NICE updated it’s dementia guidelines in 2018
the three acetylcholinesterase inhibitors (donepezil, galantamine and rivastigmine) as options for managing mild to moderate Alzheimer’s disease
memantine (an NMDA receptor antagonist) is in simple terms the ‘second-line’ treatment for Alzheimer’s, NICE recommend it is used in the following situation reserved for patients with
moderate Alzheimer’s who are intolerant of, or have a contraindication to, acetylcholinesterase inhibitors
as an add-on drug to acetylcholinesterase inhibitors for patients with moderate or severe Alzheimer’s
monotherapy in severe Alzheimer’s
Managing non-cognitive symptoms
NICE does not recommend antidepressants for mild to moderate depression in patients with dementia
antipsychotics should only be used for patients at risk of harming themselves or others, or when the agitation, hallucinations or delusions are causing them severe distress
Donepezil
is relatively contraindicated in patients with bradycardia
adverse effects include insomnia
What is Vascular dementia
-Explained by vascular causes in absence of other explanatory pathology, but AD can co-exist
-Second most common specific cause of dementia
-Prevalence increases with age: 0.4% in 60-64 age group, 4% per year above 85
-It is not a single disease but a group of syndromes of cognitive impairment caused by different mechanisms causing ischaemia or haemorrhage secondary to cerebrovascular disease
-Stroke-related VD - multi-infarct or single-infarct dementia
Subcortical VD - caused by small vessel disease
Mixed dementia - the presence of both VD and Alzheimer’s disease
Risk factors vascular dementia
History of stroke or transient ischaemic attack (TIA)
Atrial fibrillation
Hypertension
Diabetes mellitus
Hyperlipidaemia
Smoking
Obesity
Coronary heart disease
A family history of stroke or cardiovascular
Rarely, VD can be inherited as in the case of CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.
Pathophysiology and presentation of vascular dementia
-Multi-Infarct dementia: cortical infarcts associated with large vessel disease
=stepwise course with abrupt increases in severity of symptoms
-Strategic Infarcts: Subcortical ischaemic problems
[associated with small vessel disease]= gait and attention problems with change in personality
=insidious onset, gradual progression
-Focal neurological signs (hemiparesis or visual field defects, sensory or motor)
-History of strokes (x2 risk)
-Difficulty solving problems, attention, concentration, memory disturbance
-Apathy
-Disinhibition
-Seizures
-Gait
-Speech
-Emotional
Diagnosis of vascular dementia
Diagnosis is made based on:
A comprehensive history and physical examination
Formal screen for cognitive impairment
Medical review to exclude medication cause of cognitive decline
MRI scan - may show infarcts and extensive white matter changes
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
established using clinical examination and neuropsychological testing
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 of vascular dementia
General management
Treatment is mainly symptomatic with the aim to address individual problems and provide support to the patient and carers
Important to detect and address cardiovascular risk factors - for slowing down the progression
Non-pharmacological management
Tailored to the individual
Include: cognitive stimulation programmes, multisensory stimulation, music and art therapy, animal-assisted therapy
Managing challenging behaviours e.g. address pain, avoid overcrowding, clear communication
Pharmacological management
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.
There is no evidence that aspirin is effective in treating patients with a diagnosis of vascular dementia.
No randomized trials found evaluating statins for vascular dementia
Cortical Lewy body disease as a clinical syndrome
The relationship between Parkinson’s disease and Lewy body dementia is complicated, particularly as dementia is often seen in Parkinson’s disease. Also, up to 40% of patients with Alzheimer’s have Lewy bodies.
-Dementia
=Fluctuating attention/cognitive impairment
=Memory not necessarily affected in early stages; early impairments in attention and executive function rather than just memory loss
=Progressive cognitive impairment: typically occurs before parkinsonism but usually both features occur within year of each other (contrast to Parkinson’s disease where motor symptoms typically present at least one year before cognitive symptoms)
-Visual hallucinations (recurrent)
-REM sleep behaviour disorder
-Increased sensitivity to drug-induced -Parkinsonism
=Parkinsonian features (bradykinesia, rest tremor, rigidity)
Investigation and management of Cortical Lewy Body disease
-Clinical, SPECT: Widespread cortical Lewy Bodies
-Donepezil or rivastigmine are recommended first line.
-Galantamine is an option if donepezil and rivastigmine are not tolerated.
-Risperidone and haloperidol= antipsychotics
-Memantine
-Neuroleptics should be avoided: irreversible Parkinsonism (deterioration after antipsychotic)
What is FTLD and FTD?
-Clinically and neuropathologically a heterogenous group
-Linked by main involvement of frontal & temporal lobes
-Presenting with a fronto-temporal dementia syndrome
-FTLD: Fronto-Temporal Lobar Degeneration
=Essentially a pathological term
-FTD: Fronto-Temporal Dementia (pick’s disease)
=Essentially a clinical syndromic term (pattern of cognitive impairment), onset before 65
=Including association with MND
=Behavioural (loss of empathy, apathy, disordered social, sexual disinhibition) and language (progressive aphasia) variants
-Progressive non fluent aphasia (chronic progressive aphasia, CPA): non fluent speech, short utterances that are agrammatic, comprehension relatively preserved
-Semantic dementia: fluent progressive aphasia, fluent but empty and conveys little meaning, memory better for recent rather than remote events
Common features of frontotemporal lobar dementias
-Onset before 65
-Insidious onset
-Relatively preserved memory and visuospatial skills
-Personality change and social conduct problems
Other cognitive disorders/ dementias
-Parkinson’s disease dementia
-Huntington’s Disease (frontal-type cognitive impairment with dysexecutive problem and motor disorder with choreiform movements)
-HIV-associated Dementia (50% of AIDS patients)
-CJD (BSE contamination of diet)
-Pick’s disease (atrophy of frontal and temporal lobes)
