Assessing Risk Factors for Cognitive Decline and Dementia

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Age and genetics are the best known risk factors for Alzheimer’s disease. While these factors are beyond our control, we may be able to influence other risk factors involved in age-related cognitive decline and dementia. Scientists are exploring whether or not lifestyle choices, such as exercise, or certain medical conditions, such as high cholesterol, high blood pressure or diabetes, can influence risk for cognitive decline or dementia (see Testing Therapies to Treat, Delay, or Prevent Alzheimer’s Disease). For instance, recent research has examined the role played by sleep-disordered breathing—or sleep apnea—in the risk for age-related cognitive decline.

A person’s early life history can also influence Alzheimer’s disease risk. For example, studies in 2011 added to an increasing body of evidence that more years of high school and college education are associated with reduced risk of cognitive decline in old age, and that more years of education may be particularly protective for certain socioeconomic groups (see The Influence of Education and Health Disparities and Alzheimer’s Disease).


Sleep-Disordered Breathing

Sleep-disordered breathing (SDB), or sleep apnea, is a disorder primarily characterized by frequent pauses in breathing during sleep, which leads to frequent arousals from sleep and reduced blood oxygen level (hypoxemia). SDB affects up to 60 percent of older people and is associated with daytime drowsiness and increased risk of cardiovascular disease.

A study led by researchers at University of California, San Francisco, found that SDB also increases the risk of cognitive impairment in older women (Yaffe et al., 2011). The researchers assessed cognitive performance and indices of disrupted sleep, as well as measures of disordered breathing and hypoxemia, in nearly 300 women (average age, 82) who participated in the Study of Osteoporotic Fractures, over a period of 5 years. They found that women with SDB were almost twice as likely to develop mild cognitive impairment (MCI) or dementia compared to women free of the disorder.

The study suggests that the key factor leading to diminished cognition was oxygen deprivation, rather than the arousals from sleep. Treatment of sleep apnea with continuous positive airway pressure (CPAP) devices or supplemental oxygen might help prevent or delay cognitive decline in older adults.

Indeed, there is some clinical evidence for the benefits of CPAP treatment in Alzheimer’s disease. A pilot clinical trial led by researchers at George Mason University, Fairfax, VA, is underway to assess whether oxygen supplementation can delay cognitive decline in people with MCI and sleep apnea.


The Influence of Education

Higher educational attainment and larger brain size have been linked to reduced Alzheimer’s disease risk. Some researchers believe that education and brain volume are measures of “cognitive reserve”—the ability to use brain networks more efficiently or to recruit alternative networks in the face of brain degeneration and/or better overall health of brain neurons.

In a study led by researchers at the Washington University, St. Louis, education and brain volume also impacted the speed at which cognitively normal people with early signs of Alzheimer’s pathology progressed to symptomatic cognitive impairment (Roe et al., 2011). The team followed nearly 200 people aged 50 or older. All were cognitively normal at the start of the study, but some had elevated levels of tau in their cerebrospinal fluid, believed to be a biomarker of Alzheimer’s. Within that group, higher levels of education and greater brain volumes predicted slower progression to cognitive impairment over the next 3.3 years. This study supports the idea that educational level and brain volume are important predictors of rate of progression to Alzheimer’s.


Left: Early and Late Deficits in Alzheimer’s (a and e). These composite images represent the loss of gray matter—brain regions where neurons and dendrites are found—over 1.5 years in the brains of people in their 70s diagnosed with Alzheimer’s disease. Image a shows a mix of blue and red, but over 18 months, the increase in red in image b indicates the brain atrophy that is typical of Alzheimer’s disease.

Right: Percent Loss in Alzheimer’s (c and g). This composite image of the brains of a group of older people with Alzheimer’s shows many brain regions experiencing about a 15 percent loss of volume. This loss occurs as the color red, which signifies less volume, and increases dramatically from image c to image g 1 year later.

Courtesy of Paul M. Thompson, PhD, and Arthur W. Toga, PhD, Laboratory of Neuro Imaging, UCLA.


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