Dementia Flashcards
What is dementia?
Syndrome characterised by appreciable deterioration in cognition resulting in behavioural problems and impairments in the activities of daily living.
!!! What is the aetiology of dementia? (x8)
- DEGENERATIVE CAUSES: Alzheimer’s, Lewy body disease, Parkinson’s disease, Huntington’s disease, Pick’s disease
- VASCULAR CAUSES: multiple infarcts, a strategic single infarct, haemorrhage, hypoperfusion, Binswanger’s disease
- NEOPLASTIC: metastatic lesions, primary brain tumours (notably frontal tumours and of the posterior fossa)
- METABOLIC: myxoedema, vitamin B12 deficiency, thyroid disorders, Wilson’s disease
- TRAUMATIC: controversial aetiology; subdural haematoma. Trauma accelerates beta amyloid precursor production and associated with its accumulation. This is part of the pathophysiology of dementia
- INFECTIOUS: HIV, syphilis, Lyme disease, TB meningitis
- INFLAMMATORY: demyelinating diseases such as SLE, sarcoidosis and MS
- TOXIC: alcohol, lead, barbiturates
What are important differentials for memory loss when assessing for dementia? (x3)
- Mild cognitive impairment (MCI)
- Psychiatric causes of memory problems: delirium, depression, amnesia
- Neurological causes of memory problems: hydrocephalus
What is Binswanger’s disease?
AKA subcortical vascular dementia: widespread microscopic areas of damage to white matter of the brain. Rare cause of vascular dementia
What is Lewy body disease?
Spectrum disorder that includes Parkinson’s disease dementia. Disease associated with deposition of Lewy bodies and Lewy neurites in neuronal cell bodies and axons respectively. This leads to degeneration and are associated with abnormally phosphorylated neurofilaments, ubiquitin and alpha-synuclein.
What is Pick’s disease?
It is a behavioural variant of frontotemporal dementia describing Pick bodies (spherical protein aggregates) consisting of Tau fibrils, ubiquitin and tubulin. It is associated with impulsiveness, disinhibition, listlessness and apathy.
What are the risk factors for dementia? (x2)
Mild cognitive impairment (MCI), family history
What is MCI?
Newly acquired cognitive decline to an extent beyond that expected for age or education but not causing functional impairment. Insufficient to qualify for dementia diagnosis.
What are the two types of MCI?
Memory impaired for the patient’s age/education: AMNESTIC subtype of MCI. If memory is spared but the person has impairment of other cognitive domains such as language or executive function, this constitutes NON-AMNESTIC subtype of MCI.
What is the epidemiology of dementia: Prevalence? Most common cause?
1% prevalence at age of 60 and doubles every 5 years to reach 30-50% by age 85. Most common cause is Alzheimer’s disease.
What is the Amyloid hypothesis for pathophysiology of dementia?
- NORMALLY, amyloid precursor protein (APP) is cleaved by ALPHA-SECRETASE. sAPP-alpha is subsequently released and a C83 fragment remains. C83 is digested by GAMMA-SECRETASE and products are removed.
- In ALZHEIMER’S DISEASE, APP is cleaved by BETA-SECRETASE. sAPP-BETA is subsequently released and a C99 fragment remains. C99 is digested by gamma-secretase, releasing BETA-AMYLOID PROTEIN which forms toxic aggregates in and outside neurones – forming SENILE PLACQUES.
- These plaques result in an immune response which damage neurones, or they produce toxins themselves which incur damage.
What is the Tau hypothesis for pathophysiology of dementia?
- Tau proteins are embedded within microtubules of neurones. In neurones, microtubules predominantly run the length of the axon and are responsible for transport of proteins and products needed at the pre-synaptic terminal, and neuronal integrity.
- Tau proteins maintain integrity and assembly of microtubules.
- In Alzheimer’s Disease, Tau proteins are hyperphosphorylated and INSOLUBLE. Instead, they AGGREGATE to form neurofibrillary tangles intracellular. In this form, they are NEUROTOXIC which leads to neurodegeneration. Neurodegeneration is also promoted by microtubule instability.
What is the inflammation hypothesis for pathophysiology of dementia?
Microglial cells (the macrophages of the CNS) have increased activity: release inflammatory mediators and cytotoxic proteins, increase phagocytosis, and reduce their level of secretion of neuroprotective proteins –> neurodegeneration.
What screening tools are used in dementia? (x4)
- Mini Mental State Examination (MMSE): most widely used. Less than 24 indicates abnormal result and requires re-evaluation in 3-6 months to assess progressive decline.
- Alzheimer’s Disease Assessment Scale-Cognitive Section (ADAS-Cog)
- Mattis Dementia Rating Scale (MDRS)
- Montreal Cognitive Assessment (MoCA)
What are the investigations for dementia? (x6)
- Aimed at excluding treatable causes of dementia:
- BLOODS: TFTs, metabolic panels to identify metabolic causes. HIV testing also considered for those at risk
- URINE: toxicology panel for opiates, barbiturates and drugs of abuse, urinalysis for heavy metals for this with history of exposure
- CT/MRI BRAIN: cerebral atrophy in neurodegenerative disorders, tumours, infarction and subdural haematoma
- PSYCHOMETRIC TESTING: used for defining domains of impairment
- LUMBAR PUNCTURE (CSF): to assess subacute onset disease to exclude encephalitis, syphilis etc. Indicated also in dementia below 55 years of age. Amyloid and tau can also be measured
- EEG: limited utility, though may be used to differentiate depression from dementia from other causes e.g., neurodegenerative dementia is distinguished by slow background rhythm on EEG
