Ethiology

The cause of AD is unknown. Several investigators now believe that converging environmental and genetic risk factors trigger a pathophysiologic cascade that, over decades, leads to Alzheimer pathology and dementia.

The following risk factors for Alzheimer-type dementia have been identified :

• Advancing age

• Family history

• APOE 4 genotype

• Obesity

• Insulin resistance

• Vascular factors

• Dyslipidemia

• Hypertension

• Inflammatory markers

• Down syndrome

• Traumatic brain injury

Midlife hypertension is an established risk factor for late-life dementia, of which AD is the most common type. A brain autopsy study evaluating the link between hypertension and AD found that patients using beta-blockers to control blood pressure had fewer Alzheimer's-type brain lesions on autopsy compared to patients taking no drug therapy or those taking other medications.

In addition, epidemiologic studies have suggested some possible risk factors (eg, aluminum, previous depression) and some protective factors (eg, education, long-term use of nonsteroidal anti-inflammatory drugs ).

Prevention

There are no proven modalities for preventing AD, but evidence, largely epidemiologic, suggests that healthy lifestyles can reduce the risk of developing the disease; the following may be protective :

• Physical activity

• Exercise

• Cardiorespiratory fitness

• Diet: Although no definitive dietary recommendations can be made, in general, nutritional patterns that appear beneficial for AD prevention fit the Mediterranean diet

Prognosis

AD is initially associated with memory impairment that progressively worsens. Over time, patients with AD can also display anxiety, depression, insomnia, agitation, and paranoia. As their disease progresses, patients with AD come to require assistance with basic activities of daily living, including dressing, bathing, and toileting. Eventually, difficulties with walking and swallowing may develop. Feeding may be possible only by gastrointestinal tube, and difficulty swallowing may lead to aspiration pneumonia.

The time from diagnosis to death varies from as little as 3 years to as long as 10 or more years. Patients with early-onset AD tend to have a more aggressive, rapid course than those with late-onset AD. The primary cause of death is intercurrent illness, such as pneumonia

Management

The mainstay of therapy for patients with Alzheimer disease (AD) is the use of centrally acting cholinesterase inhibitors to attempt to compensate for the depletion of acetylcholine (ACh) in the cerebral cortex and hippocampus. A partial N -methyl-D-aspartate (NMDA) antagonist is approved for treatment of moderate and severe AD. Various medications are used for treatment of secondary symptoms of AD, including antidepressants, anti-anxiety agents, and antipsychotic agents.

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

Most studies of psychotropic drugs for AD have demonstrated no or limited efficacy. However, many issues make interpretation of data from these studies difficult. For example, Huperzine A, a naturally occurring sesquiterpene alkaloid compound found in the firmoss Huperzia serrata, has been investigated as a possible treatment for diseases characterized by neurodegeneration – particularly Alzheimer's disease. A 2013 meta-analysis found that huperzine A may be efficacious in improving cognitive function, global clinical status, and activities of daily living for individuals with Alzheimer’s disease. However, due to the poor size and quality of the clinical trials reviewed, huperzine A should not be recommended as a treatment for Alzheimer’s disease until further high quality studies confirm its beneficial effects.

Current pharmacologic research in AD focuses principally on the development of disease-modifying drugs that can slow or reverse the progression of AD. Targets of these investigational agents have included beta-amyloid production, aggregation, and clearance, as well as tau phosphorylation and assembly. To date, none of these drugs has demonstrated efficacy in phase III trials. Potential surgical treatments in the future may include the use of devices to infuse neurotrophic factors, such as growth factors, to palliate AD.