4PAHPBIO Psychology and the Brain Week 8
Psychology BSc Year 1 Neurodegeneration
NEURODEGENERATION
8.1 THE PREVALENCE, SYMPTOMS AND RISK FACTORS OF
ALZHEIMER’S DISEASE.
CHARACTERISTICS OF ALZHEIMER’S DISEASE
• Alzheimer’s disease (AD) is the most common form of dementia, accounting for approximately 62%
of cases worldwide
o It affects about 10% of those over 65 and nearly 50% of those over 85
• In the UK, the prevalence is around 1 in 127, with a higher prevalence in women than men
• Annual incidence is approximately one-quarter of the prevalence, indicating an average disease
duration of around four years
• Globally, 44 million people live with dementia, projected to triple by 2050, with the highest
increases in low- and middle-income countries
RISK FACTORS
Non-Modifiable Risk Factors
Age
• The risk of developing Alzheimer’s doubles every five years after age 65
Genetic Components
• Early-onset Alzheimer’s is strongly associated with autosomal dominant mutations in genes
involved in amyloid-beta (Aβ) production and a defective long form of Aβ to be produced
o The APP gene is located on chromosome 21, which is also implicated in Down’s syndrome,
leading to earlier amyloid deposition (Martinez et al., 1993; Farlow et al., 1994)
o Mutations in presenilin genes (PS1 and PS2) affect γ-secretase function, promoting amyloid
plaque formation (Hardy, 1997)
o Misfolded Aβ can also accelerate plaque spread through cell-to-cell transmission, as
demonstrated in experimental studies (Kane et al., 2000)
• Late-onset Alzheimer’s is primarily associated with the APOE-e4 allele, which increases Aβ
clearance from the extracellular space (Roses, 1997; Bu, 2010)
Down’s Syndrome
• Individuals with trisomy 21 produce more amyloid-beta due to an extra copy of the APP gene,
leading to earlier and more extensive amyloid deposition
Modifiable Risk Factors
Traumatic Brain Injury
• The strongest non-genetic risk factor for AD, particularly in individuals carrying the APOE-e4 allele
(By, 2010)
o Those who have sustained closed-head injuries reveal a widespread distribution of amyloid
plaques are a risk for Alzheimer’s
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, 4PAHPBIO Psychology and the Brain Week 8
Psychology BSc Year 1 Neurodegeneration
Lifestyle Factors
• Cardiovascular risk factors, including obesity, hypertension, high cholesterol, and diabetes,
increase the likelihood of developing AD, especially in APOE-e4 carriers
• Smoking, excessive alcohol consumption, and social isolation also contribute to risk
• Physical exercise and higher education levels serve as protective factors
• Level of education and cognitive activity can delay Aβ accumulation and slow cognitive decline, as
shown in both human and animal studies (Billings et al., 2007)
DIAGNOSING ALZHEIMER’S
• Only around half of those with dementia receive a diagnosis (in the UK)
• It can be difficult to distinguish symptoms of Alzheimer’s from the natural process of ageing, such
as cognitive decline and poor memory
• A clinical review or assessment with the patient and informant is needed, along with tests to rule
out other health conditions, such as blood tests, MRIs, CT and Amyloid PET scans
SYMPTOMS
• Progressive loss of memory, resembling anterograde amnesia, primarily affecting recent events
• Impaired cognitive functions, including poor judgement and abstract thinking
• Language difficulties, such as forgetting words or using incorrect terms, as well as problems in
speaking, reading, writing, and understanding
• Disorientation in time and space, leading to confusion about location and the current period in life
• Difficulty with daily functioning, including misplacing items and impaired problem-solving ability
• Personality changes, including mood swings and irritability
8.2 THE PROPOSED PATHOLOGY UNDERLYING ALZHEIMER’S
DISEASE.
PATHOLOGY
Brain Structure
• AD causes severe degeneration of the hippocampus, entorhinal cortex, and neocortex, particularly
in the frontal and temporal lobes
o This degeneration leads to cortical tissue loss, wider sulci, and macroscopic brain atrophy
• Up to 20% of patients with AD also exhibit Lewy bodies (Breitve et al., 2014)
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