A comprehensive textbook review of the pathology, clinical features, diagnosis, treatment and nursing management of Alzheimer's disease.
It is the most common cause of dementia. Dementia is not one specific disease; rather, it describes a syndrome involving significant deterioration in cognitive abilities such as memory, language, reasoning, judgement and problem-solving.
Alzheimer's disease is particularly associated with progressive loss of neurons and neuronal connections, abnormal accumulation of beta-amyloid and tau proteins, and eventual cerebral atrophy.
| Type | Description |
|---|---|
| Early-onset AD | Symptoms begin before 65 years of age. It accounts for a minority of cases. Rare familial forms may be associated with strongly penetrant genetic mutations. |
| Late-onset AD | Symptoms begin from 65 years of age onwards. It accounts for the majority of cases and involves complex interactions among ageing, genetics and other risk factors. |
The hippocampus is located within the medial temporal lobe and plays a major role in learning and consolidation of new memories. Damage to hippocampal networks explains why inability to remember recently learned information is a prominent early manifestation.
The entorhinal cortex communicates extensively with the hippocampus and other cortical regions. It contributes to memory and spatial processing and is among the regions affected early in the disease process.
As neurodegeneration spreads, areas involved in language, reasoning, judgement, planning and behaviour become progressively affected.
Alzheimer's disease develops through a complex sequence of molecular, cellular and neuronal abnormalities. Two of its most recognisable pathological hallmarks are beta-amyloid plaques and neurofibrillary tangles composed of abnormal tau.
Amyloid precursor protein is normally present within neuronal cell membranes. When it is processed, smaller protein fragments are produced.
Certain beta-amyloid peptides can accumulate and aggregate in the extracellular space between neurons. Increasing aggregation eventually contributes to the formation of amyloid plaques.
These abnormalities are associated with impaired synaptic communication and other damaging biological responses within affected neuronal networks.
Figure 1. Real histopathological appearance of an
amyloid plaque in the hippocampus in Alzheimer's disease.
H&E stain. Mikael Häggström, M.D.; CC0/Public Domain,
via Wikimedia Commons.
Tau is a protein normally associated with microtubules. Microtubules form part of the neuron's structural and intracellular transport system.
In Alzheimer's disease, abnormal biochemical changes affect tau. The protein separates from microtubules and accumulates within neurons.
Abnormal tau ultimately forms twisted intracellular structures called neurofibrillary tangles. Disruption of microtubules interferes with transport of nutrients and other essential materials within neurons.
Figure 2. Histopathological demonstration of
neurofibrillary tangles in the hippocampus.
Mikael Häggström, M.D.; CC0/Public Domain,
via Wikimedia Commons.
Neurons communicate through specialised connections called synapses. Alzheimer's disease progressively interferes with this communication.
Loss of synaptic connections reduces the efficiency of neuronal networks and contributes directly to deterioration in cognition.
Microglia and astrocytes normally support neurons and help remove damaged material. Altered inflammatory responses and impaired clearance mechanisms may contribute to further neuronal dysfunction and injury.
As the disease progresses, increasing numbers of neurons become dysfunctional and eventually die. Loss of neurons and their connections causes affected regions of the brain to shrink.
Memory-related structures are affected early, while progressive disease eventually involves broader cortical areas.
- Increasing age — the strongest recognised risk factor.
- Family history and genetic susceptibility.
- Rare inherited genetic mutations in some early-onset families.
- Cardiovascular and cerebrovascular disease.
- Other interacting biological and environmental influences.
- Difficulty remembering newly learned information.
- Repeated questions or conversations.
- Misplacing commonly used objects.
- Difficulty finding words.
- Reduced ability to plan complicated tasks.
- Difficulty managing finances.
- Reduced judgement.
- Subtle changes in mood or personality.
- Increasing memory impairment.
- Disorientation to time and place.
- Difficulty recognising familiar individuals.
- Progressive language impairment.
- Difficulty dressing or maintaining personal hygiene.
- Agitation or irritability.
- Sleep disturbance.
- Wandering.
- Increasing dependence on caregivers.
- Profound cognitive impairment.
- Markedly reduced communication.
- Difficulty recognising close relatives.
- Loss of independent mobility.
- Urinary or faecal incontinence.
- Dysphagia.
- Complete or near-complete dependence for daily care.
Diagnosis requires a comprehensive clinical assessment rather than a single test. The clinician determines the nature of the cognitive problem, its progression and its effect on independent functioning.
The history should establish the onset and progression of memory, language, behavioural and functional changes.
Information from a relative or caregiver can be especially useful because some patients may have limited awareness of their cognitive impairment.
Cognitive testing may assess memory, attention, orientation, language, executive function and visuospatial ability. Examples of screening instruments include the MMSE and MoCA.
A cognitive screening score should be interpreted together with the clinical history and functional assessment.
Appropriate investigations are used to identify alternative or contributing causes of cognitive decline. Depending on the clinical presentation, assessment may include thyroid function, vitamin B12 and relevant metabolic investigations.
CT and MRI are useful for investigating structural abnormalities and alternative neurological disorders. Alzheimer's disease may be associated with progressive cerebral and medial temporal atrophy.
Specialist assessment can incorporate biomarkers that provide evidence of Alzheimer's pathology. Depending on availability and clinical circumstances, these may include cerebrospinal-fluid biomarkers, amyloid PET, tau PET and validated blood biomarkers.
Figure 3. PET scans comparing a normal older
adult's brain with the brain of an older adult with Alzheimer's
disease. National Institute on Aging, NIH; Public Domain.
- Vascular cognitive impairment and dementia.
- Dementia with Lewy bodies.
- Frontotemporal dementia.
- Delirium.
- Depression.
- Medication-related cognitive impairment.
- Vitamin B12 deficiency.
- Thyroid dysfunction.
- Normal-pressure hydrocephalus.
- Other structural neurological disorders.
Management aims to preserve remaining cognitive and functional abilities, maintain independence for as long as possible, improve safety and quality of life, manage symptoms, prevent complications and support caregivers.
- Regular physical activity appropriate to ability.
- Meaningful cognitive and recreational activity.
- Social interaction.
- Consistent daily routines.
- Adequate nutrition and hydration.
- Healthy sleep routines.
- Correction of hearing and visual impairment when possible.
- Fall prevention.
- Home-safety assessment.
- Caregiver education and support.
Donepezil, rivastigmine and galantamine inhibit acetylcholinesterase and increase the availability of acetylcholine at cholinergic synapses.
They may provide symptomatic benefit in appropriately selected patients but do not cure Alzheimer's disease.
Important nursing observations include gastrointestinal symptoms, appetite and weight changes, pulse, dizziness, syncope and individual treatment response.
Memantine is an NMDA receptor antagonist that modulates abnormal glutamatergic neurotransmission.
It is used particularly in moderate-to-severe Alzheimer's disease according to individual clinical circumstances and applicable guidelines.
Anti-amyloid monoclonal antibody therapy represents a newer disease-modifying approach for carefully selected people with early Alzheimer's disease in settings where such therapy is approved and available.
These treatments may slow clinical decline in selected patients; they do not cure Alzheimer's disease or restore neurons already lost.
Specialist assessment and monitoring are necessary because important adverse effects, including amyloid-related imaging abnormalities, can occur.
Nursing care should focus on maintaining safety, preserving remaining function, reducing distress, maintaining nutrition and hydration, preventing complications and supporting the patient's family or caregivers.
- Assess orientation and cognitive function.
- Assess short- and long-term memory.
- Evaluate communication ability.
- Determine ability to perform activities of daily living.
- Assess gait, balance and fall risk.
- Monitor nutritional status and weight.
- Assess hydration.
- Assess chewing and swallowing.
- Observe sleep patterns.
- Assess behavioural changes.
- Review medication adherence and adverse effects.
- Assess caregiver stress and support.
Approach calmly and establish eye contact. Use short, clear sentences and give one instruction at a time.
Allow adequate time for the patient to process information and respond. Avoid repeatedly arguing about an incorrect memory when reassurance and redirection can achieve the clinical objective.
Encourage the patient to perform tasks that remain within their ability. Assistance should be provided when necessary without unnecessarily removing opportunities for independent activity.
- Keep walking areas clear.
- Provide adequate lighting.
- Assess gait and balance.
- Provide appropriate supervision.
- Assess wandering risk.
- Reduce environmental hazards.
Monitor intake and body weight. A calm eating environment can help reduce distraction. Provide assistance while maintaining as much independent feeding as safely possible.
Advanced disease can impair swallowing. Patients showing signs of dysphagia require appropriate assessment because aspiration, malnutrition and dehydration can become important complications.
Before assuming that agitation is simply caused by dementia, consider possible unmet needs or triggers such as pain, hunger, fear, overstimulation, sleep disturbance, constipation or acute illness.
Teach caregivers about disease progression, communication, nutrition, environmental safety, medication supervision and symptoms requiring professional assessment.
Caregiver wellbeing should also be considered because long-term care can create substantial physical, emotional and social strain.
Always preserve dignity. Speak directly to the patient, explain care before beginning, provide manageable choices and avoid infantilising language.
- Falls and accidental injury.
- Malnutrition and weight loss.
- Dehydration.
- Dysphagia.
- Aspiration.
- Reduced mobility.
- Pressure injury.
- Infection.
- Increasing functional dependence.
- Caregiver exhaustion and psychosocial burden.
Alzheimer's disease is progressive, although the rate of progression differs considerably between individuals.
As cognitive and functional abilities decline, increasing assistance is usually required with medication management, finances, transportation, hygiene, mobility, nutrition and other activities of daily living.
- Alzheimer's disease is the most common cause of dementia.
- It is a progressive neurodegenerative disease and not simply normal ageing.
- The two classic pathological hallmarks are beta-amyloid plaques and tau neurofibrillary tangles.
- The hippocampus and entorhinal cortex are affected relatively early.
- Loss of recently acquired memory is therefore a characteristic early manifestation.
- Progression eventually affects language, judgement, behaviour, mobility and self-care.
- Diagnosis requires history, cognitive and functional assessment and appropriate investigation.
- Donepezil, rivastigmine and galantamine are cholinesterase inhibitors.
- Memantine is an NMDA receptor antagonist.
- Major nursing priorities are safety, communication, independence, nutrition, hydration, dignity and caregiver support.
Educational note: This material is intended for nursing and medical education. Clinical assessment and treatment should follow current local professional guidelines and individual patient needs.