Alzheimer disease (AD) is an acquired disorder of cognitive and behavioral impairment that markedly interferes with social and occupational functioning. It is an incurable disease with a long and progressive course. In AD, plaques develop in the hippocampus, a structure deep in the brain that helps to encode memories, and in other areas of the cerebral cortex that are used in thinking and making decisions. Whether plaques themselves cause AD or whether they are a by-product of the AD process is still unknown.
Essential update: MRI plus biomarkers may be key to finding early Alzheimer disease
In a recent cross-sectional, longitudinal cohort study of 207 older adults with normal cognition, investigators found a correlation between decay in the default mode network (DMN), as observed on resting-state functional connectivity magnetic resonance imaging (rs-fcMRI), and levels of 2 cerebrospinal fluid (CSF) biomarkers of early AD. This suggests that rs-fcMRI may be an effective noninvasive means of detecting early asymptomatic AD.
In the study, Ances and colleagues found that decreases in DMN integrity had an independent association with reductions in CSF amyloid beta 42 and increases in CSF phosphorylated tau 181 . Moreover, the posterior cingulate cortex and the medial temporal lobe, 2 regions that are frequently impacted by AD, were found to have the most prominent decreases in functional connectivity.
Signs and symptoms
Preclinical Alzheimer disease
A patient with preclinical AD may appear completely normal on physical examination and mental status testing. Specific regions of the brain (eg, entorhinal cortex, hippocampus) probably begin to be affected 10-20 years before any visible symptoms appear.
Mild Alzheimer disease
Signs of mild AD can include the following:
- Memory loss
- Confusion about the location of familiar places
- Taking longer to accomplish normal, daily tasks
- Trouble handling money and paying bills
- Compromised judgment, often leading to bad decisions
- Loss of spontaneity and sense of initiative
- Mood and personality changes; increased anxiety
Moderate Alzheimer disease
The symptoms of this stage can include the following:
- Increasing memory loss and confusion
- Shortened attention span
- Problems recognizing friends and family members
- Difficulty with language; problems with reading, writing, working with numbers
- Difficulty organizing thoughts and thinking logically
- Inability to learn new things or to cope with new or unexpected situations
- Restlessness, agitation, anxiety, tearfulness, wandering, especially in the late afternoon or at night
- Repetitive statements or movement; occasional muscle twitches
- Hallucinations, delusions, suspiciousness or paranoia, irritability
- Loss of impulse control: Shown through behavior such as undressing at inappropriate times or places or vulgar language
- Perceptual-motor problems: Such as trouble getting out of a chair or setting the table
Severe Alzheimer disease
Patients with severe AD cannot recognize family or loved ones and cannot communicate in any way. They are completely dependent on others for care, and all sense of self seems to vanish.
Other symptoms of severe AD can include the following:
- Weight loss
- Seizures, skin infections, difficulty swallowing
- Groaning, moaning, or grunting
- Increased sleeping
- Lack of bladder and bowel control
In end-stage AD, patients may be in bed much or all of the time. Death is often the result of other illnesses, frequently aspiration pneumonia.
Diagnosis
Means of diagnosing AD include the following:
- Clinical examination: The clinical diagnosis of AD is usually made during the mild stage of the disease, using the above-listed signs
- Lumbar puncture: levels of tau and phosphorylated tau in the cerebrospinal fluid are often elevated in AD, whereas amyloid levels are usually low; at present, however, routine measurement of CSF tau and amyloid is not recommended except in research settings
- Imaging studies: Imaging studies are particularly important for ruling out potentially treatable causes of progressive cognitive decline, such as chronic subdural hematoma or normal-pressure hydrocephalus
Management
All drugs approved by the US Food and Drug Administration (FDA) for the treatment of AD are symptomatic therapies that modulate neurotransmitters, either acetylcholine or glutamate. The standard medical treatment for AD includes cholinesterase inhibitors (ChEIs) and a partial N-methyl-D-aspartate (NMDA) antagonist.
The following classes of psychotropic medications have been used to treat the secondary symptoms of AD, such as depression, agitation, aggression, hallucinations, delusions, and sleep disorders
- Antidepressants
- Anxiolytics
- Antiparkinsonian agents
- Beta-blockers
- Antiepileptic drugs: For their effects on behavior
- Neuroleptics
