CHICAGO, July 29 -- The rate of new cases of mild cognitive impairment in patients over 70 is higher than previously expected, results from the Mayo Clinic Study of Aging showed.

Initially healthy participants developed mild cognitive impairment at a rate of 5.3% a year (95% CI 4.3% to 6.5%), two to three times higher than the rate of new cases of dementia in the same population, Ronald Petersen, M.D., Ph.D., of the Mayo Clinic in Rochester, Minn., reported at the International Conference on Alzheimer's Disease here.

"If we extrapolate Alzheimer's incidence rates to mild cognitive impairment, we would expect perhaps 1% to 2% per year," said Dr. Petersen, who is also the vice chair of the Alzheimer's Association's medical and scientific advisory council, "but our findings were substantially higher than that."

The rate increased from 3.5% (95% CI 2.4% to 5%) in participants ages 70 to 79 to 7.2% (95% CI 5.5% to 9.3%) in those ages 80 to 89.

In addition, men were nearly twice as likely as women to develop mild cognitive impairment (HR 1.92, 95% CI 1.22 to 3.02).

Although mild cognitive impairment may represent a transitional phase to various forms of dementia, it is unknown how often it occurs in a population-based setting, the researchers said.

To find out, they turned to the Mayo Clinic Study on Aging, which randomly selected participants ages 70 to 89 from Olmsted County, Minn., in 2004; 1,786 participants were available for analysis.

Each participant underwent a baseline examination that included an assessment of cognitive function and a neurological exam. In addition, the researchers interviewed a close acquaintance of each participant. Follow-up was conducted in 15-month intervals.

The rates of mild cognitive impairment in men and women were 6.2% (95% CI 4.7% to 8.1%) and 4.4% (95% CI 3.1% to 6%), respectively.

Compared with women, men were more likely to have amnestic mild cognitive impairment (HR 2.00, 95% CI 1.12 to 3.57) as well as the non-amnestic subtype (HR 1.82, 95% CI 0.87 to 3.81), although the latter comparison did not reach statistical significance.

"These results underscore the urgency of developing new and better strategies to create disease-modifying therapies for Alzheimer's," Dr. Petersen said. "In addition, for public health purposes, we need to know how many people are cognitively impaired and potentially on the road to Alzheimer's."

Ralph Nixon, M.D., Ph.D., of New York University, and a member of the medical and scientific advisory council of the Alzheimer's Association, said, "This both magnifies the urgency of the problem of Alzheimer's disease and extends it to an even larger population but also gives some hope of early intervention that would target this population at an earlier stage of the disease."

According to Dr. Petersen, the findings may not be generalizable to populations outside of the predominantly white population of northern European descent of Olmsted County.

He noted, however, that the results of worldwide studies of mild cognitive impairment were not "drastically" different from those of the current study.

The findings are particularly important considering the shifting population distribution associated with aging baby boomers, Dr. Petersen said.

CHICAGO, July 29 -- Diabetics who took both insulin and other medications for the disease had fewer plaques associated with Alzheimer's disease than other patients, researchers said here.

In a postmortem study, patients on combination treatment had significantly fewer beta-amyloid plaques (P=0.014) than diabetics who were on one treatment alone or patients who did not have diabetes, Michal Schnaider Beeri, Ph.D., of Mount Sinai School of Medicine in New York, reported at the International Conference on Alzheimer's Disease.

Overall, the combination group had about 80% fewer plaques compared with the other groups combined.

However, there were no significant between-group differences in the occurrence of neurofibrillary tangles.

"These results suggest that the combination [of insulin and other diabetes medications] … may beneficially influence Alzheimer's-related brain changes," Dr. Beeri said. "This also points to biological pathways in the brain, such as insulin signaling, that might be a focus for developing new treatment strategies."

Because diabetes has been associated with a greater risk of mild cognitive impairment and Alzheimer's disease in epidemiological studies, the researchers expected to see more plaques when they examined the brains of diabetics.

In a previous study by Dr. Beeri's group, however, that wasn't the case. In fact, they found fewer plaques. Other neuropathological studies have failed to find any association between diabetes and the number of plaques or neurofibrillary tangles.

Dr. Beeri and her colleagues hypothesized that the treatments for diabetes may influence the neuropathology of Alzheimer's.

To test the hypothesis, the researchers studied 248 brains -- 124 from diabetics and 124 from non-diabetics -- from the Mount Sinai School of Medicine Brain Bank. Most of the specimens came from the Jewish Home and Hospital in Bronx, N.Y., and the two groups were matched by age, sex, and severity of dementia.

The mean age of the patients at death was 81.2 and 57.3% were female. The mean clinical dementia rating was 2.4, indicating moderate to severe dementia.

Non-diabetics had slightly lower body mass indices but the difference was not statistically significant.

Of the diabetics, 29 were not on any medication, 49 were taking insulin only, 28 were taking medications other than insulin -- like glyburide or metformin -- and 18 were taking both insulin and another diabetes medication.

The researchers examined the extent of plaques and neurofibrillary tangles in several neocortical regions and in the hippocampus, entorhinal cortex, and amygdala using the CERAD (Consortium to Establish A Registry for Alzheimer's Disease) neuropathological battery.

The group that was on combination treatment for diabetes had significantly fewer beta-amyloid plaques in the entorhinal cortex (P=0.003), amygdala (P=0.009), and overall (P=0.014) compared with the other groups, which did not differ significantly from each other.

The differences approached statistical significance in the hippocampus (P=0.057) and the combined neocortical measure (P=0.052).

When the researchers additionally controlled for APOE e4 genotype, BMI, and fasting glucose at the time of nursing home admission, there was no change in the findings.

Dr. Beeri acknowledged some limitations of the study, including the inability to determine causation and potential confounding. Nor could the survivor effect be ruled out, she said.

Nevertheless, Dr. Beeri said, the results suggest that diabetes medications may influence biological pathways involved in beta-amyloid processing.

Older patients who take statins may be at lower risk of developing dementia, according to findings from a prospective cohort study.


Statin users were 44% less likely to develop dementia and cognitive impairment than nonusers after controlling for other factors (P=0.010), reported Mary N. Haan, Dr.P.H., of the University of Michigan here, and colleagues in the July 29 issue of Neurology.

However, the findings were not enough to suggest that patients should take a statin unless necessary for other health reasons, the investigators cautioned.

Although these findings add evidence in favor of statins for cognitive outcomes, this area of research has been controversial with little agreement between studies, the researchers said.



At baseline, statin users and nonusers were similar, except that statin users were slightly younger, more educated, and more likely to have been born in the U.S. and covered by medical insurance.

Statin users were also more likely to have a history of diabetes and higher mean baseline cognitive scores on the Modified Mini-Mental State Examination.

During more than five years of follow-up, 130 participants developed dementia or cognitive impairment without dementia.

Of the 82 patients with dementia, 48% had possible or probable Alzheimer's disease, 23% had undetermined etiology, 13% had ischemic vascular dementia, and 13% had mixed Alzheimer's or vascular dementia.

Statin users had a 43% lower rate of dementia and non-dementia cognitive impairment than nonusers (hazard ratio 0.577, 95% confidence interval 0.376 to 0.886, P=0.012).

After controlling for baseline diabetes and stroke, statins remained associated with a 48% lower rate of dementia and non-dementia cognitive impairment (HR 0.518, 95% CI 0.336 to 0.797, P=0.003).

Further adjustment for education, smoking status, and apolipoprotein E (APOE-e4) genotype attenuated the association only slightly to a 44% lower risk compared with nonusers (HR 0.564, 95% CI 0.365 to 0.872, P=0.010).

The protective effect of statins on dementia held for both high functioning individuals with above-average cognitive scores on the Modified Mini-Mental State Examination (HR 0.546, 95% CI 0.327 to 0.912) and those with below average scores (HR 0.444, 95% CI 0.200 to 0.988).

The researchers cautioned that the findings may have been biased by differential loss to follow-up, indication bias, or competing risks.

However, they noted that statin use didn't appear to have an impact on survival (HR 0.92, 95% CI 0.69 to 1.20).


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