QuestionSBA
QuestionChoice
This is incorrect because this describes the finding in vascular dementia. Patients typically have a step-wise decline in function following a cerebrovascular event. They usually have cardiovascular risk factors such as hypertension, hypercholesterolaemia or diabetes.
53120
d
Multiple infarcts with white matter damage
QuestionChoice
This is incorrect because this describes the finding in normal pressure hydrocephalus. The classic symptoms for this condition can be remembered by wet, weird and wobbly: urinary incontinence, dementia, and recurrent falls. Note that this is a type of reversible dementia.
53121
e
Enlarged ventricles
QuestionChoice
This patient has Alzheimer's disease. Histopathology would demonstrate beta amyloid plaques and neurofibrillary tangles made of tau protein.
53117
a
Amyloid plaques
QuestionChoice
Alpha-synuclein inclusions are found within the substantia nigra in Parkinson's disease and Lewy Body Dementia. These conditions are characterised by a typical triad of bradykinesia, rigidity and a resting tremor, which this patient does not have. Lewy Body Dementia is also classically associated with visual hallucinations, typically of Lilliputian bodies.
53118
b
Alpha-synuclein
QuestionChoice
This is incorrect because this describes the finding in frontotemporal dementia. Frontotemporal dementia typically affects patients who are younger than 65 years and causes changes in their behaviour and personality. Memory and visuospatial skills are relatively preserved.
53119
c
Frontal and temporal lobe atrophy
Concept
Chapter
# Summary

Alzheimer's disease, the most common form of dementia, is a progressive neurodegenerative disorder that leads to cognitive decline, memory impairment, and a range of behavioural and psychological symptoms. Its impact extends beyond the individual, affecting families and healthcare systems worldwide. This comprehensive guide explores the key aspects of Alzheimer's disease, from its definition and pathophysiology to clinical features, diagnostic considerations, management approaches, and prognosis. Adherence to NICE guidelines ensures evidence-based care for patients with this challenging condition.

# Definition

Alzheimer's disease is a chronic, neurodegenerative disorder characterized by the progressive accumulation of abnormal protein deposits, primarily amyloid plaques and tau tangles, in the brain. This leads to the deterioration of cognitive function, memory loss, and various behavioural and psychological symptoms.


# Epidemiology

Alzheimer's disease is a global health concern, with an increasing prevalence as the population ages. It is estimated that millions of individuals worldwide are affected, with higher incidence rates in older age groups. Women are more commonly affected than men, and several genetic and environmental factors influence disease risk.


# Pathophysiology


Alzheimer's disease is a complex and progressive neurodegenerative disorder characterized by distinct pathophysiological hallmarks. These hallmarks are responsible for the gradual decline in cognitive function and the characteristic clinical features observed in affected individuals.

1. **Amyloid Plaques:** The accumulation of beta-amyloid protein fragments outside nerve cells in the form of plaques is a hallmark feature. These abnormal protein deposits are believed to disrupt neuronal communication, trigger inflammation, and ultimately lead to cell death.

2. **Tau Tangles:** Inside nerve cells, abnormal tau protein accumulates, forming neurofibrillary tangles. These tangles interfere with the transport of essential nutrients within neurons, contributing to their dysfunction and eventual demise.

3. **Neuronal Loss and Brain Atrophy:** As the disease progresses, significant neuronal loss occurs, particularly in brain regions responsible for memory and cognitive function, such as the hippocampus and the cerebral cortex. This loss is associated with brain atrophy, visible on imaging studies.

4. **Neurotransmitter Imbalance:** Alzheimer's disease disrupts the balance of neurotransmitters, particularly acetylcholine, which plays a crucial role in memory and learning. Reduced acetylcholine levels further contribute to cognitive decline.

5. **Inflammatory Response:** Chronic neuroinflammation, characterized by the activation of microglia and astrocytes, is a prominent feature in Alzheimer's disease. Inflammation may exacerbate neuronal damage and contribute to the progression of the disease.

# Risk Factors

Several factors influence an individual's risk of developing Alzheimer's disease. These include:

- **Age:** Advanced age is the most significant risk factor, with the incidence of Alzheimer's disease increasing exponentially after the age of 65.

- **Genetic Predisposition:** Mutations in specific genes, such as the apolipoprotein E (APOE) gene, increase the risk of developing Alzheimer's disease. Additionally, individuals with Down's syndrome are at a higher risk due to a triplication of chromosome 21, which carries the amyloid precursor protein (APP) gene.

- **Family History:** Having a first-degree relative with Alzheimer's disease can increase one's susceptibility.

- **Cardiovascular Risk Factors:** Conditions like hypertension, diabetes, obesity, and hypercholesterolemia have been associated with an elevated risk of Alzheimer's disease.

- **Lifestyle Factors:** Physical inactivity, smoking, and a diet high in saturated fats may contribute to increased risk.

- **Traumatic Brain Injury:** A history of head injuries, particularly repeated concussions, has been linked to a higher risk of developing Alzheimer's disease.

- **Low Educational Attainment:** Lower levels of education may be associated with an increased risk.

Understanding these risk factors and their relationship to the disease's pathophysiology is crucial for early identification, prevention, and management of Alzheimer's disease.

# Clinical Features

Alzheimer's disease is characterized by a constellation of cognitive and behavioural symptoms, which may include:

* **Memory Impairment:** Early in the disease, individuals often experience difficulties in recalling recent events and conversations.
* **Language Impairment:** This may manifest as difficulty finding words, struggling to express oneself, and, in later stages, aphasia.
* **Executive Dysfunction:** Impaired ability to plan, organize, and carry out tasks, leading to difficulties in activities of daily living.
* **Behavioural Changes:** Individuals may exhibit agitation, aggression, or apathy, sometimes accompanied by mood swings and irritability.
* **Psychological Symptoms:** Hallucinations, delusions, and paranoia can occur, particularly in later stages of the disease.
* **Disorientation:** Affected individuals may become disoriented in familiar surroundings, unable to recognize places or people.
* **Loss of Motor Skills:** In advanced stages, motor skills decline, leading to difficulties with mobility and self-care.

# Differential Diagnosis


1. **Vascular Dementia:** Cognitive impairment in vascular dementia often presents suddenly and is associated with a history of cerebrovascular events.

2. **Lewy Body Dementia:** Visual hallucinations and fluctuating cognitive impairment are more common in Lewy body dementia.

3. **Frontotemporal Dementia:** This condition typically presents with profound behavioural and personality changes, often affecting social conduct.

4. **Mild Cognitive Impairment (MCI):** MCI is a transitional state between normal cognitive aging and dementia. Unlike Alzheimer's, MCI may not significantly impact daily functioning.

5. **Normal Age-Related Cognitive Decline:** Age-related cognitive changes are common but do not interfere significantly with daily activities.

# Investigations

Diagnosing Alzheimer's disease may involve a series of assessments, including:

- **History** - including a functional history, which may be informed using  a structured instrument such as the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) or the Functional Activities Questionnaire (FAQ). A collateral history may be necessary, and a risk assessment should also be taken.
- Assess cognitive decline using an approved  scoring tool such as MMSE, MOCA, 10-point Cognitive Screener (10-CS), 6-item Cognitive Impairment Test (6-CIT), 6-item Screener, Memory Impairment Screen (MIS), Mini-Cog, Test Your Memory (TYM) 
- **Examination** - physical examination including a full neurological examination looking for abnormaliities in coordination, gait, sensation and motor signs.
- **Blood tests** - to rule out reversible causes, this is known as a confusion screen and is often done in primary care. It includes FBC, U&E, LFTs, CRP/ESR, Ca2+, TFTs, B12, folate, syphilis, HIV. If there is an acute onset of symptoms delirium should be considered as this is a different pathway.
- Once reversible causes are ruled out and a diagnosis of dementia is still suspected, refer to a specialist dementia diagnostic service (such as a memory clinic or community old age psychiatry service. Here, a full functional assessment is carried out and the patient will be referred for **neuroimaging**, such as CT or MRI.
	- **Brain Imaging:** Magnetic resonance imaging (MRI) and positron emission tomography (PET) scans can reveal brain atrophy and the presence of amyloid plaques.
	- **Cerebrospinal Fluid Analysis:** May be used to detect specific biomarkers associated with Alzheimer's disease.

# Management

- **Non-Pharmacological Approaches:** Psychological interventions, cognitive stimulation therapy, and occupational therapy can help manage behavioural and psychological symptoms.

- **Support for Caregivers:** Education and support for family members and caregivers are vital to help them navigate the challenges of providing care.

- **Patient-Centered Care:** Tailoring interventions to the individual's needs and preferences, while ensuring their safety and well-being.
- **Pharmacological Intervention:** Medications, such as cholinesterase inhibitors (e.g. donepezil) and N-methyl-D-aspartate (NMDA) receptor antagonists (e.g. memantine), may be prescribed to manage cognitive symptoms.
	- Pharmacological treatments may have modest benefits, and include the cholinesterase inhibitors rivastigamine, galantamine, and donpezil in mild-moderate dementia, and the NMDA inhibitor memantine in severe dementia (as classified using the MMSE score: severe:  <10; moderate: 10-20; mild: 21-26/30. 
	- If there is evidence of behavioral and psychological symptoms of dementia (BPSD), low-dose risperidone may be started


# NICE Guidelines

[NICE CKS - Dementia](https://cks.nice.org.uk/topics/dementia/)

# References

[NHS UK - Alzheimer's Disease](https://www.nhs.uk/conditions/alzheimers-disease/)

[Alzheimer's Association](https://www.alz.org/alzheimers-dementia/what-is-alzheimers)






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Alzheimer's disease
Topic
57
Geriatrics
10684
Alzheimer's disease is characterised by the presence of amyloid plaques and neurofibrillary tangles in the brain.
A 74-year-old female presents to the memory clinic after referral by her GP. Her family report that her memory for recent events is worsening, and she is struggling to manage her finances, remember words, and recognise objects. Her childhood memories remain relatively preserved.

Given the most likely diagnosis, which of the following is the most likely pathological finding?
a