Description
Alzheimer’s Disease (AD) is a progressive, neurodegenerative disease that causes significant cognitive impairment, including memory loss, confusion, and difficulties with thinking and behaviour. It is the most common cause of dementia, and is characterised pathologically by the presence of amyloid plaques and neurofibrillary tangles in the brain.
Pathogenesis
The pathogenesis of AD involves the deposition of extracellular amyloid-beta plaques and the formation of intracellular neurofibrillary tangles composed of hyperphosphorylated tau protein. These pathological changes are associated with neuronal loss and synaptic damage, particularly in the hippocampus and other regions involved in memory.
Epidemiology, Risk Factors & Associations
AD affects more than 30 million people worldwide and accounts for 60-80% of dementia cases. Age is the most significant risk factor, with incidence rates doubling every five years after age 65. Other risk factors include female sex, a family history of AD, Down’s syndrome, mild cognitive impairment, and carrying the APOE4 allele. Cardiovascular risk factors such as hypertension, diabetes, and obesity also increase the risk of AD.
Clinical Features
The initial symptom of AD is typically forgetfulness, especially for recent events (short-term memory loss). As the disease progresses, patients experience difficulties with language (aphasia), carrying out motor activities (apraxia), recognition (agnosia), and executive functions such as planning and organising. Behavioural changes, including agitation and aggression, may also occur.
Complications
Complications of AD include an increased risk of falls, pressure ulcers, infections, malnutrition, and decreased overall health due to physical inactivity and poor nutrition. There is also a significant impact on caregivers, who may experience high levels of stress and other mental health issues.
Pathological Features
Histopathology
- Key histopathological features of AD are amyloid plaques and neurofibrillary tangles.
- Amyloid plaques are extracellular deposits of amyloid-beta peptide
- Meurofibrillary tangles are intracellular accumulations of hyperphosphorylated tau protein.
Biochemistry
- Cerebrospinal fluid analysis is notable for elevated tau protein levels and decreased beta-amyloid levels
Radiological Features
General Features
The most notable feature of AD on imaging is brain atrophy, which initially involves the medial temporal lobe (including the hippocampus) and later becomes more widespread. It is usually bilateral and asymmetric.
CT
- Bilateral asymmetric brain atrophy
- Medial temporal lobe and hippocampus atrophy in early disease.
- Generalised atrophy in late stages.
MRI
- T1: High signal in the white matter due to gliosis and loss of neurons.
- T2/FLAIR: Shows atrophy with ventricular enlargement and sulcal widening.
PET
- FDG: Corresponding hypometabolism
Diagnosis
Diagnosis of AD is primarily based on clinical features and cognitive testing. Neuroimaging and cerebrospinal fluid analysis can provide supportive evidence. Neuropsychological testing can confirm cognitive impairment, and genetic testing may be useful in familial cases.
Differential Diagnosis
- Vascular dementia: Sudden onset, stepwise progression, and presence of focal neurological signs.
- Lewy body dementia: Visual hallucinations, Parkinsonism, and fluctuating cognitive impairment.
Management
There is no cure for AD, but certain medications (e.g., cholinesterase inhibitors and memantine) can alleviate symptoms. Non-drug interventions, such as cognitive stimulation therapy, may also be beneficial. Management is usually coordinated by a neurologist or geriatrician, with support from a multidisciplinary team.