Early Stages Of Age-Related Macular Degeneration Associated With Smoking, Cholesterol Levels

June 15, 2010

Adapted from the JAMA and Archives Journals

Early-stage age-related macular degeneration appears to be related to modifiable risk factors, including smoking and low levels of high-density lipoprotein (HDL or "good" cholesterol), according to a report in the June issue of Archives of Ophthalmology, one of the JAMA/Archives journals. The condition appears uncommon before age 55 but the risk increases with age thereafter.

Most studies assessing the prevalence of age-related macular degeneration (AMD) have focused on middle- and older-age adults, according to background information in the article. "To our knowledge, accurate estimates of prevalence of AMD among adults younger than 40 years are lacking," the authors write. "Such information is important for understanding the relationships of risk factors to AMD across the age spectrum and for identifying factors that might affect this disease earlier in life."

Ronald Klein, M.D., M.P.H., of the University of Wisconsin, Madison, and colleagues assessed 2,810 individuals age 21 to 84 participating in the Beaver Dam Offspring Study. The presence and severity of drusen—yellow or white deposits in the retina, an early sign of AMD—was determined, along with that of other characteristics of AMD.

Early AMD was present in 3.4 percent of the participants, with rates varying from 2.4 percent in those age 21 to 34 to 9.8 percent in those age 65 years and older. Besides age, other factors associated with increased risk for AMD included being male, smoking more heavily for a longer period of time, and being hearing impaired, whereas having higher levels of HDL cholesterol was associated with reduced risk.

Factors not associated with early AMD included blood pressure, body mass index, physical activity level, history of heavy drinking, white blood cell count or total cholesterol level.

Drusen were present in the macula—the area in the retina responsible for sharp vision—in 63.3 percent of the participants, and the frequency of drusen increased with age. When age was considered, men and women had approximately the same number of drusen.

"In summary, the Beaver Dam Offspring Study data provide precise estimates of the prevalence of various signs of AMD (soft drusen, pigmentary abnormalities) over a wide spectrum of ages from the third to the ninth decade of life," the authors write. "They demonstrate that early AMD onset may occur in midlife. Some modifiable factors (smoking status and serum HDL cholesterol level) associated with AMD in older cohorts were associated with early AMD in this cohort of middle-aged adults."

"The higher frequency of AMD in people aged 65 or older in an aging population makes this an important public health problem," they conclude. "Further information regarding the natural history of AMD and its risk factors, especially early in life, is important for developing preventive approaches to it."

Mayo Clinic Researchers Find Dementia In Diabetics Differs From Dementia In Non-Diabetics

July 15, 2010

On behalf of its donors, Alzheimer's Disease Research (ADR), a program of the American Health Assistance Foundation (AHAF), is very proud to have funded Dr. Mary Haan for this very important study.

Adapted from the Mayo Clinic

Researchers from Mayo Clinic's Florida campus say that dementia in some diabetics appears to be caused often by vascular disease in the brain, and the dementia that develops in people without diabetes is more likely associated with deposition of the plaque seen in people with Alzheimer's disease.

The findings will be presented at the Alzheimer's Association International Conference on Alzheimer's Disease 2010 meeting in Honolulu. They resulted from a study conducted among persons with Mexican ancestry but may have relevance to other populations, say the researchers. Also involved in the study were investigators from the University of California, San Francisco.

"This helps in understanding diabetes and dementia," says Mayo neurologist Neill Graff-Radford, M.D., who is presenting the findings. "It suggests that the vascular dementia seen in diabetics, which appears to be related to small blood vessel disease and strokes, can potentially be averted if development of diabetes is prevented."

The results agree with a number of autopsy studies conducted on patients with dementia and diabetes, in which vascular abnormalities were found to be related to the dementia but the Alzheimer's pathology of plaque and tangles was not, he says.

The findings also suggest that an experimental blood test to predict development of Alzheimer's disease may be more accurate than some studies of people with dementia have suggested, because those studies included participants with diabetes, says Dr. Graff-Radford. "We now propose that future studies of this test should take into account diabetic status," he says.

The test is based on discoveries made by Mayo neuroscientists, which measure the ratio of two different kinds of amyloid beta proteins in blood. Plaque found in the brains of Alzheimer's disease patients at autopsy started when the toxic form of amyloid beta, known as Aß42, began to be deposited.

Dr. Graff-Radford and his colleagues earlier discovered that if the Aß42 to Aß40 ratio in blood was low, Aß42 was likely being deposited in the brain and that Alzheimer's disease was developing. Five independent studies have confirmed that hypothesis. One found that the risk of Alzheimer's disease was up to 10 times greater in people with a low Aß42/Aß40 ratio. Three additional studies did not find this, and Dr. Graff-Radford suggests those studies may have included enough diabetic patients to skew the results.

The findings also make sense biologically, Dr. Graff-Radford says. Both the insulin hormone and amyloid beta proteins are degraded by the insulin-degrading enzyme (IDE). He adds that if the blood contains excess insulin, as is the case in diabetics, then IDE preferentially degrades insulin instead of amyloid. "That means there would be higher levels of both Aß42 and Aß40 in the blood of diabetics," he says.

This research comes from a sub-study of an ongoing National Institutes of Health-funded study, the Sacramento Area Latino Study on Aging (SALSA), which includes 1,789 people, primarily Mexican-American. In this study, the researchers analyzed Aß42/Aß40 ratios in 211 participants who developed dementia and 403 "controls"—participants matched in age and gender who remained cognitively normal. Researchers found that among non-diabetics, only the Aß42/Aß40 low ratio was associated with dementia. In diabetics, the ratio of Aß42 to Aß40 was not decreased.

This study was supported by the National Institutes of Health, the American Health Assistance Foundation, the Robert and Clarice Smith and Abigail Van Buren Alzheimer's Disease Research Program.

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