Risk Factors for Alzheimer's disease (AD)

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Aging

Aging is still the largest risk for becoming demented, with the prevalence doubling every 5 years between ages 65 and 85 ( 1% at age 65, 5% at age 75 and 15-25% at age 85).

Family history of AD

Family history of dementia in a first degree relative ( sibling or parent) increases the risk of developing AD fourfold. In persons with two or more affected first degree relatives, the risk increases 7-8 fold. The mechanism is presumably due to the higher risk of transmitting one or more alleles which accelerate the pathogenetic mechanisms involved in AD.

Family history of Down syndrome

A family of history of Down syndrome may increase the risk for developing AD by two-to-three fold. The persons without Down syndrome who have developed AD in these families did not have triplication of chromosome 21.

History of depression

A history of depression more than 10 years prior to the onset of AD approximately doubles the risk. The mechanism is unknown, but the reduced activity of frontal and temporal lobes in depression may make these areas more vulnerable to pathological mechanisms.

Estrogen deficiency

Estrogen deficiency in postmenopausal women has been implicated in a variety of studies as increasing the risk of AD and possibly other dementias. This has been demonstrated mostly through studies of hysterectomized (including ovaries) women. The mechanism of action may be through estrogen's influence on nerve growth factor, which supports acetyl choline-secreting neurons that are severely affected in AD.

Lack of education

An uneducated person has about twice the risk of developing dementia due to AD or vascular disease by age 75 when compared to someone with at least an 8th grade education. The mechanism of this effect may be synaptic strengthening of frequently used brain regions ( use-dependent plasticity), which may also explain why some persons with specific talents or hobbies, such as golf, playing music, playing cards, drawing cartoons show preservation of such highly used skills even if they develop AD.

HEAD TRAUMA

Either severe single head injuries producing prolonged unconsciousness, or repeated head injuries approximatly double the risk for AD. The mechanism may relate to increased expression of PS-1 gene products and to increased production of diffuse beta amyloid following trauma. An increased pool of diffuse, soluble beta amyloid may increase the opportunity for the formation of insoluble beta amyloid, which is known to be neurotoxic and known to be present in neuritic plaques, one of the hallmarks of AD neuropathology.

Other possible risks for AD

Other factors which may increase the risk for AD include:

A history of increased alcohol consumption.
A history of heart attack especially in women (vascular dementia AD). The mechanism may be due to increased production of diffuse beta-amyloid plaques.
Maternal age over 40.
Family history of Parkinson's disease.
hypothyroidism

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