Pharmacologic treatments for Alzheimer's disease (AD) may improve symptoms but have not been shown to prevent AD onset. Primary prevention therefore remains the goal. Although preventing AD by managing risk factors such as age or genetics is beyond our control (Box 1, page 24), we can do something about other factors.
Nonmodifiable risk factors for Alzheimer's disease
Age remains the strongest risk factor for dementia, particularly for Alzheimer's disease (AD). (a) The risk of developing AD doubles every 5 years after age 65 and approaches 50% after age 85. (b)
Family history is a risk factor for AD, although true familial AD accounts for <5% of cases. (c) When diseases show a familial pattern, either genetics, environmental factors, or both may play a role. Patients with a first-degree relative with dementia have a 10% to 30% increased risk of developing the disorder. (d)
Genetic factors play a role in both early-onset and late-onset AD. Early-onset AD (before age 65) accounts for 6% to 7% of cases. (e) From this small pool of patients, only 13% exhibit clear autosomal dominant transmission over >1 generation. (f) Three gene mutations have been associated with early-onset AD:
* 30% to 70% are in the presenilin-1 gene
* 10% to 15% are in the amyloid precursor protein gene
* <5% are in the presenilin-2 gene. (g), (h)
For late-onset AD (after age 65), the strongest evidence for a genetic risk factor exists for the epsilon 4 allele of the apolipoprotein E gene (APOE e4). (i) This genotype has been linked to the development of AD and possibly to vascular dementia. (j), (k) In contrast, the epsilon 2 allele of APOE may exert a protective effect in AD. (l) APOE e3, the most common allele, appears to play a neutral role in the development of AD.
Source: For reference citations, see this article at CurrentPsychiatry.com
This article summarizes the findings of many studies that address AD prevention and includes an online-only bibliography for readers seeking an in-depth review. The evidence does not support a firm recommendation for any specific form of primary prevention and has revealed hazards associated with estrogen therapy and nonsteroidal anti-inflammatory drugs (Box 2, page 25). Most important, it suggests that you could reduce your patients' risk of developing AD by routinely supporting their mental, physical, and social health.
Estrogen and NSAIDs: Not recommended for AD protection
Estrogen. Before the Women's Health Initiative (WHI) study, various trials of the effects of estrogen therapy on the development of Alzheimer's disease (AD) in women age [greater than or equal to]65 showed inconsistent results. In the randomized, placebo-controlled WHI Memory Study, conjugated equine estrogen, 0.625 mg/d, plus medroxyprogesterone acetate, 2.5 mg/d, did not prevent mild cognitive impairment or improve global cognitive function and was associated with an increased risk for probable dementia. (a) Based on this evidence, conjugated equine estrogen with or without medroxyprogesterone is not recommended as therapy to protect cognitive function in older women.
NSAID therapy. Cytokine-mediated inflammation may play a role in neurodegenerative disorders and cognitive impairment in the elderly. Nonsteroidal anti-inflammatory drugs (NSAIDs), including cyclooxygenase-2 (COX-2) inhibitors, have been studied for a possible protective effect against AD and cognitive decline, (b) possibly by lowering amyloidogenic proteins. (c) A 1-year randomized controlled trial by the Alzheimer's Disease Cooperative Consortium found no significant differences in cognition scores of patients treated with once-daily rofecoxib, 25 mg, or twice-daily naproxen sodium, 220 mg, when compared with placebo. (d) Similarly, naproxen and celecoxib did not prevent AD in the randomized, controlled Alzheimer's Disease Anti-inflammatory Prevention Trial (ADAPT). …