Higher glucose levels had a significant association with an increased
risk of dementia in older, nondiabetic individuals, investigators
reported.
Nondiabetic patients who developed dementia had a mean blood glucose level of 115 mg/dL in the preceding 5 years compared with 100 mg/dL in similar patients who did not have dementia.
The higher levels were associated with almost a 20% increase in the hazard for dementia, reported Paul K. Crane, MD, of the University of Washington in Seattle, and colleagues.
Adding to the established association between diabetes and dementia, diabetic patients who subsequently developed dementia also had significantly higher average glucose levels as compared with diabetic patients who did not develop dementia (P=0.002), they wrote online in the New England Journal of Medicine.
"We found that higher glucose levels were associated with an increased risk of dementia in populations without and with diabetes," Crane's group stated. "The findings were consistent across a variety of sensitivity analyses."
"These data suggest that higher levels of glucose may have deleterious effects on the aging brain," they added. "Our findings underscore the potential consequences of temporal trends in obesity and diabetes and suggest the need for interventions that reduce glucose levels."
Though consistent with much of the literature on dementia, the findings conflict with those of another recent study, which showed an association between dementia and hypoglycemia.
Diabetes is a recognized risk factor for dementia, and obesity is the leading risk factor for diabetes. However, the relationship among obesity, diabetes, and dementia has remained unclear, as studies of the association have yielded mixed results. In an effort to bring some clarity to the subject, Crane and colleagues retrospectively evaluated longitudinal clinical data on a large prospective cohort.
The study included 2,581 dementia-free individuals randomly selected from the Group Health Cooperative. All participants were 65 or older at enrollment from 1994 through 1996. An additional 811 participants enrolled from 2000 through 2002.
Participants were asked to return at 2-year intervals for dementia evaluation, and 2,067 of the participants had at least one follow-up visit.
The 2,067 patients had been members of Group Health for at least 5 years prior to enrollment in the study, and they had at least five measurements of blood glucose or glycated hemoglobin (HbA1c) over 2 or more years before joining the study.
Dementia was assessed at follow-up visits by means of the Cognitive Abilities Screening Instrument, which has scores ranging from 0 to 100 with higher scores reflecting better cognitive function. Diagnoses of dementia or Alzheimer's disease were based on research criteria.
The final analysis encompassed 35,264 glucose measurements and 10,208 measurements of HbA1c obtained from 839 men and 1,228 women who had a baseline mean age of 76. The participants included 232 patients with diabetes.
During a median follow-up of 6.8 years, 524 participants developed dementia, consisting of 74 with diabetes and 450 without. Patients without diabetes and who developed dementia had significantly higher average glucose levels in the 5 years before diagnosis of dementia (P=0.01). The difference translated into a hazard ratio of 1.18 (95% CI 1.04-1.33).
Among the patients with diabetes, glucose levels averaged 190 mg/dL in those who developed dementia versus 160 mg/dL in those who did not. The difference represented a 40% increase in the hazard for dementia (HR 1.40, 95% CI 1.12-1.76).
The study had some limitations including reliance on available clinical laboratory measurements obtained at irregular intervals for estimates of glucose levels.
Still, the findings are consistent with those from previous studies and probably do not come as a surprise to researchers in the field, said Suzanne DeLaMonte, MD, of Brown University in Providence, R.I., who was not involved in the study.
"This concept has been demonstrated in humans and experimental animals," DeLaMonte told MedPage Today via email. "The connection was made at least 8 years ago and finally has reached the mainstream. I'm very happy about this because it opens doors for the development of new [treatments] or retooling of old treatments for neurodegeneration."
Whether the association between dementia and blood sugar could go in the opposite direction remains unclear and is a "tricky" proposition to address, she continued.
"There are emerging data showing that brain 'abnormalities' dysregulate food intake which of course could lead to 'irresponsible' eating [which would lead to] hyperglycemia," said DeLaMonte.
"However, for the most part, I think insulin resistance can overlap in brain and other organs. The hyperglycemia [not yet diabetes] reflects insulin resistance and should be used as a very easy screen for trouble looming, not just risk for diabetes."
Nondiabetic patients who developed dementia had a mean blood glucose level of 115 mg/dL in the preceding 5 years compared with 100 mg/dL in similar patients who did not have dementia.
The higher levels were associated with almost a 20% increase in the hazard for dementia, reported Paul K. Crane, MD, of the University of Washington in Seattle, and colleagues.
Adding to the established association between diabetes and dementia, diabetic patients who subsequently developed dementia also had significantly higher average glucose levels as compared with diabetic patients who did not develop dementia (P=0.002), they wrote online in the New England Journal of Medicine.
"We found that higher glucose levels were associated with an increased risk of dementia in populations without and with diabetes," Crane's group stated. "The findings were consistent across a variety of sensitivity analyses."
"These data suggest that higher levels of glucose may have deleterious effects on the aging brain," they added. "Our findings underscore the potential consequences of temporal trends in obesity and diabetes and suggest the need for interventions that reduce glucose levels."
Though consistent with much of the literature on dementia, the findings conflict with those of another recent study, which showed an association between dementia and hypoglycemia.
Diabetes is a recognized risk factor for dementia, and obesity is the leading risk factor for diabetes. However, the relationship among obesity, diabetes, and dementia has remained unclear, as studies of the association have yielded mixed results. In an effort to bring some clarity to the subject, Crane and colleagues retrospectively evaluated longitudinal clinical data on a large prospective cohort.
The study included 2,581 dementia-free individuals randomly selected from the Group Health Cooperative. All participants were 65 or older at enrollment from 1994 through 1996. An additional 811 participants enrolled from 2000 through 2002.
Participants were asked to return at 2-year intervals for dementia evaluation, and 2,067 of the participants had at least one follow-up visit.
The 2,067 patients had been members of Group Health for at least 5 years prior to enrollment in the study, and they had at least five measurements of blood glucose or glycated hemoglobin (HbA1c) over 2 or more years before joining the study.
Dementia was assessed at follow-up visits by means of the Cognitive Abilities Screening Instrument, which has scores ranging from 0 to 100 with higher scores reflecting better cognitive function. Diagnoses of dementia or Alzheimer's disease were based on research criteria.
The final analysis encompassed 35,264 glucose measurements and 10,208 measurements of HbA1c obtained from 839 men and 1,228 women who had a baseline mean age of 76. The participants included 232 patients with diabetes.
During a median follow-up of 6.8 years, 524 participants developed dementia, consisting of 74 with diabetes and 450 without. Patients without diabetes and who developed dementia had significantly higher average glucose levels in the 5 years before diagnosis of dementia (P=0.01). The difference translated into a hazard ratio of 1.18 (95% CI 1.04-1.33).
Among the patients with diabetes, glucose levels averaged 190 mg/dL in those who developed dementia versus 160 mg/dL in those who did not. The difference represented a 40% increase in the hazard for dementia (HR 1.40, 95% CI 1.12-1.76).
The study had some limitations including reliance on available clinical laboratory measurements obtained at irregular intervals for estimates of glucose levels.
Still, the findings are consistent with those from previous studies and probably do not come as a surprise to researchers in the field, said Suzanne DeLaMonte, MD, of Brown University in Providence, R.I., who was not involved in the study.
"This concept has been demonstrated in humans and experimental animals," DeLaMonte told MedPage Today via email. "The connection was made at least 8 years ago and finally has reached the mainstream. I'm very happy about this because it opens doors for the development of new [treatments] or retooling of old treatments for neurodegeneration."
Whether the association between dementia and blood sugar could go in the opposite direction remains unclear and is a "tricky" proposition to address, she continued.
"There are emerging data showing that brain 'abnormalities' dysregulate food intake which of course could lead to 'irresponsible' eating [which would lead to] hyperglycemia," said DeLaMonte.
"However, for the most part, I think insulin resistance can overlap in brain and other organs. The hyperglycemia [not yet diabetes] reflects insulin resistance and should be used as a very easy screen for trouble looming, not just risk for diabetes."
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