Dementia

Question 1

Describe the methods used for dementia diagnosis and know the clinical presentations of different dementias

Answer 1

Dementia is a syndrome of progressive decline in cognitive and social functions. Objective cognitive decline without impairment in ADL is syndromically labelled as Mild Cognitive Impairment. People wth MCI are at increased risk of dementia although the majority do not progress within 5 years

Diagnosis

• Observe a patient
• Take a collateral history: Questioning about the patient’s memory, orientation, language abilities, executive function and changes in personality or behaviour. IQCODE score of >3.44.
• Perform cognitive tests: General practitioner assessment of Cognition (GPAOG) or six-item cognitive impairment test (6CIT) are often used in primary care, where as the Mini-Mental State Examination (MMSE) are used for a more thorough evaluation. Alertness, attention and concentration, memory both short and long term, language, visuospatial function and executive function
• Perform appropriate investigations: Comprehensive assessment by a neuropsychologist, structural CT or MRI scans (for vascular health) to exclude other causes of cognitive decline such as tumours or strokes, and can show patterns of brain atrophy for diagnosis of dementia subtypes
• Blood tests to rule out vitamin deficiencies or thyroid dysfunction

Clinical Features

1. Alzheimer’s Disease (AD): Typically present with memory impairment, especially difficulty remembering recently learnt information, which progresses to affect other domains of cognition such as language and executive functions.
2. Vascular Dementia: Often presents with a stepwise deterioration in cognitive function, associated with a history of strokes or chronic ischaemia - exhibit significant executive dysfunction
3. Dementia with Lewy Bodies (DLB): Characterised by fluctuating cognition, prominent visual hallucinations, REM sleep behaviour disorder, parkinsonian movement symptoms and sensitivity to antipsychotic medication
4. Frontotemporal Dementia (FTD): Presents with changes in behaviour and personality or progressive language impairment
5. Parkinson’s Disease Dementia (PDD): Occurs in the later stages of Parkinson’s disease and is marked by impaired memory, attention and executive function, in addition to movement symptoms

Question 2

Basic Causes of Dementia and treatment

Answer 2

1. Alzheimer’s Disease: Characterised by amyloid beta plaques and tau protein tangles leading to neurodegeneration (Sahin et al., 2013; Mudher et al., 2004). Treat with anti-tau therapies
2. Vascular Dementia: Resulting from vascular pathology affecting brain’s blood supply
3. Dementia with Lewy Bodies and Parkinson’s Disease Dementia: Involving abnormal aggregation of the protein alpha-synuclein. Cognitive decline, posterior cortical and executive function, attention & speed. Visual hallucinations and Parkinsonism
4. Frontotemporal Dementia: Stemming from tau or TDP-43 protein deposition.

Treatment

• Alzheimer’s disease and dementia with Lewy bodies respond to cholinesterase inhibitors such as Donepezil and NMDA-antagonist like Memantine (glutamate for memory)
• Donepezil efficacy shown in AD2000 trial

Question 3

Understand what are the main risk factors for dementia and what can be modified to improve patient outcomes

Answer 3

• Vascular health influences dementia risk (hypertension, obesity, diabetes and hyperlipidemia)
• Lifestyle choices
• Education and Cognitive Engagement
• Social Support
• SPRINT-MIND (JAMA, 2019)

Question 4

Be aware of some clinical trials and their successes or otherwise in treatment

Answer 4

Amyloid-Targeting Therapies:

• Aducanumab: targets amyloid-beta plaques in the brain. Clinical trial showed that it could reduce plaque burden as evidenced by amyloid PET imaging (Sevigny et al., 2016).

Anti-Tau Therapies:

• Kinase inhibitors to reduce Tau Phophorylation, anti-tau antibodies

SPRINT-MIND Study:

• Effects of intensive blood pressure control on cognitive outcomes, reduction in mild cognitive impairment thus probable dementia reduction (JAMA 2019).

Cholinesterase Inhibitors:

• For AD and DLB, Donepezil showed efficacy in AD2000 trial

NMDA antagonists

• For AD, like Memantine (McShane et al., 2006)