QuestionSBA
QuestionChoice
Although this patient has COPD, there is no requirement for spirometry testing prior to initiation of Donepazil
31966
d
Perform spirometry testing
QuestionChoice
Although Donepazil is primarily excreted renally, there is no indication this man has impaired renal function, and there is no routine requirement to check renal function prior to initiating Donepazil
31967
e
Perform blood tests for baseline urea and electrolytes
QuestionChoice
Although this patient has COPD, there is no requirement for a routine chest x-ray prior to initiation of Donepazil
31965
c
Perform a chest x-ray
QuestionChoice
This patient has no focal neurological signs so there is no indication for a CT head at this stage
31964
b
Refer for a computed tomography (CT) scan of the head
QuestionChoice
This patient likely has Alzheimer's disease. Donepazil is an acetylcholinesterase inhibitor which can prolong the QT-interval (QTc). Therefore it is important to perform a 12 lead ECG and document baseline heart rhythm and QTc interval prior to initiation
31963
a
Electrocardiogram (ECG)
QuestionComment
Before starting the patient on an alzheimers medication, shouldnt a CT scan be done to rule out organic causes? I see why we should do an ECG before commencing the medication, but there is no formal diagnosis of dementia so surely the correct answer is CT?
9567
QuestionComment
My guess is because the neuro exam was entirely normal and the Hx/symptoms are very much in line with Alzheimer's so no need for a CT? But I agree think a CT would be appropriate
11597
User
subscriber
Neoplasia Pudendal
QuestionComment
no focal neurology therefore: no
25976
User
subscriber
Kinase Power
User
subscriber
Nikki
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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Before starting Donepezil, an ECG is important to assess the baseline heart rhythm and QTc interval, as the medication can potentially prolong the QT interval and increase the risk of arrhythmias.
A 85 year old man is seen at the neurology clinic with his daughter. The daughter reports that he has been increasingly forgetful, has a shortened attention span compared to his usual self and has become very clumsy. She says that this has been a gradual decline over several months. The patient denies any changes in mood or any suicidal ideation.

His only significant past medical history is chronic obstructive pulmonary disease (COPD) for which he takes salbutamol PRN. He has no significant psychiatric history.

On examination, he has normal tone of his upper and lower limbs, a normal gait, and normal power throughout.

The neurologist decides to start him on Donepazil. Which investigation should be performed prior to commencing this medication?
a