Dementia and Alzheimer's Disease Flashcards
What are the hallmarks of the ageing brain?
Mattson, M and P. and Arumugam T.V (2018)
Oxidative Damage
Mitochondrial Dysfunction
Impaired molecular waste disposal
Impaired DNA repair
Aberrant Neuronal Activity
Glial cell activation and inflammation
Impaired adaptive stress response signalling
Dysregulated neuronal calcium homeostasis
What is Dementia?
Umbrella term for loss of memory and other thinking abilities severe enough to interfere with daily life
What is Alzheimer’s Disease?
A progressive mental deterioration that can occur in middle or old age, due to generalised degeneration of the brain
Most common cause of premature senility
What is the most common form of Dementia?
Alzheimers disease
How do we diagnose Alzheimer’s Disease?
SCD (subjective)
MCI (mild)
Typical presentation (mild)
Atypical presentation (regional)
What is MCI?
Mild cognitive impairment
What are the history factors of SCD?
Age at onset (1)
Clinical course (2)
Dominant symptom (3)
Psychiatric symptoms (4)
1) N/A
2) Slow
3) Memory
4) 1 or mild
What are the history factors of MCI
Age at onset (1)
Clinical course (2)
Dominant symptom (3)
Psychiatric symptoms (4)
1) 65+
2) Slow
3) Memory
4) None or mild
What are the history factors of typical presentation?
Age at onset (1)
Clinical course (2)
Dominant symptom (3)
Psychiatric symptoms (4)
1) 65+
2) Slow
3) Memory
4) None or mild
What are the history factors of atypical presentation?
Age at onset (1)
Clinical course (2)
Dominant symptom (3)
Psychiatric symptoms (4)
1) <65
2) Fast or stepwise
3) Language, Behaviour, Social Cognition, Executive Function
4) None or mild or severe
Does SCD, MCI, Typical presentation and Atypical presentation require specialised assessment?
SCD- No
MCI- No
Typical Presentation- No
Atypical Presentation- Yes
What are the basic assessments of SCD like?
Cognitive Screening (1)
Functional Assessments (2)
Clinical Examination (3)
1) Normal
2) Normal
3) Normal
What are the basic assessments of MCI like?
Cognitive Screening (1)
Functional Assessments (2)
Clinical Examination (3)
1) Abnormal
2) Loss of autonomy
3) Normal
What are the basic assessments of typical presentation?
Cognitive Screening (1)
Functional Assessments (2)
Clinical Examination (3)
1) Normal/ Abnormal
2) Loss of autonomy
3) Normal
What are the basic assessments of atypical presentation?
Cognitive Screening (1)
Functional Assessments (2)
Clinical Examination (3)
1) Normal/ Abnormal
2) Loss of autonomy
3) Normal/ Abnormal
How do we diagnose Alzheimer’s Disease?
Patient History taken by GP
Mental Ability Tests or Cognitive Assessments
How does “Patient History taken by GP” diagnose Alzheimer’s Disease?
How and when symptoms stated- do they affect daily living
Pre-existing conditions
Medicine or supplements being taken
How does “Mental Ability Tests or Cognitive Assessments” diagnose Alzheimer’s Disease?
Short and Long-term memory
Concentration and attention span
Language and communication skills
Awareness of time and place (orientation)
What is MMSE?
Mini Mental State Examination
What are the advantages of Mini Mental State Examination?
Relatively quick and easy to perform
Requires no additional equipment
Can provide a method of monitoring deterioration over time
What is the disadvantages of Mini Mental State Examination?
Biased against people with poor education due to elements of language and mathematical testing
Bias against visually impaired
Limited examination of visuospatial cognitive ability
Poor sensitivity at detected mild/early dementia
How do you diagnose Alzheimer’s Disease?
Blood tests for other conditions
- Liver and kidney function
- HbA1c for diabetes
- Vitamin (B12) and mineral (folate) levels
Dementia brain scran
- MRI
- CT scan
What is an MRI scan used for?
Shrinkage of specific regions
- Frontal and Temporal lobes
What is an CT scan used for?
Tumour or stroke
- Not used for structural information
What biomarker methods can be used in the diagnosis of Alzheimer’s Disease?
Positron emission tomography
Cerebrospinal fluid
High sensitivity blood tests
Genetic screening
What do biomarkers do?
Allow measurement of what is happening inside the living body
They do not rely on symptoms for diagnosis
What is positron emission tomography?
Radioactive tracers to measure:
- Glucose
- Amyloid-beta
- Tau accumulation
What is cerebrospinal fluid?
Lumbar puncture to measure protein concentrations
- Low AB1-42
- High phosphorylated Tau
- High NF-L
What are high sensitivity blood tests?
Lumbar puncture to measure protein concentrations
- Low AB1-42
- High phosphorylated Tau
- High NF-L
Not validated
Highly specialised
What is genetic screening?
APOE alleles
Family history
Rare genetic mutations
What are the pathological hallmarks of AD?
Amyloid-Beta accumulation
- Neurofibrillary tangles
- Neurodegeneration
- Synapse degeneration
What are the risk factors for AD- Non-modifiable protective factors?
Serrano- Pozo. A and Growdon J.H. 2019
Genetics
- APOEe2
What are the risk factors for AD- Non-modifiable risk factors?
Serrano- Pozo. A and Growdon J.H. 2019
Genetics
- APOEe4
Aging
What are the risk factors for AD- modifiable protective factors?
Serrano- Pozo. A and Growdon J.H. 2019
Education attainment
Mediterranean Diet
Physical exercise
Moderate alcohol intake
Intellectual and Social Activities
What are the risk factors for AD- Modifiable risk factors?
Serrano- Pozo. A and Growdon J.H. 2019
Vascular risk factors:
- Hypertension
- Diabetes
- Obesity
- Smoking
What are the midlife factors influencing dementia in line with the 12-risk factor life-course model of dementia prevention?
Livingston et al
Hearing loss- 8%
Traumatic brain injury- 3%
Hypertension- 2%
Alcohol >21 units per week- 1%
Obesity- 1%
What are the later life factors influencing dementia in line with the 12-risk factor life-course model of dementia prevention?
Livingston et al 2020
Smoking- 5%
Depression- 4%
Social isolation- 4%
Physical inactivity- 2%
Air pollution- 2%
Diabetes- 1%
According to the 12-risk factor life-course model, how much do modifiable risk factors account for the worldwide dementias?
Livingston et al 2020
40%= potentially modifiable
60%= risk unknown
What is familial Alzheimer’s Disease?
Early-onset from 35y/o
Aggressive pathogenesis
Autosomal dominant
PSEN1, PSEN2 and APP mutations
This is not same as a genetic risk factor
How does low PA influence AD?
Tan et al. 2017
It is a major risk factor
Hazard ratio= 1.50
- Appears to be a threshold for PA and dementia risk
How does a sedentary lifestyle influence AD?
Yan et al. 2020
It is a major risk factor
30% increased risk of dementia in sedentary populations irrespective of age, sex, education level or ethnicity
Why don’t all exercise interventions work for people with Alzheimer’s disease?
Poorly designed trials:
- Intervention timing
- Outcome measures
- Mode/ Intensity of exercise (adherence)
