Alzheimer’s Pathology Reduced With Combined Diabetes Therapy
NEW YORK, September 9 (Reuters Health)—In a postmortem study of patients with Alzheimer’s disease, diabetic subjects treated with both insulin and oral hypoglycemic agents had lower neuritic plaque densities than did other diabetics and nondiabetics, new research shows.
In several studies, type 2 diabetes has been identified as a risk factor for Alzheimer’s disease. The link between diabetes and Alzheimer’s neuropathology, by contrast, is less clear, according to the report in the September 2 issue of Neurology.
The current study, conducted by Dr. M. S. Beeri, from Mount Sinai School of Medicine in New York City, and colleagues, involved an analysis of neuritic plaques and neurofibrillary tangles in brain specimens from 124 diabetics and 124 nondiabetics.
The diabetic group consisted of 29 patients who had never used antidiabetic agents, 49 who had received insulin only, 28 treated with agents other than insulin, and 18 treated with both insulin and oral antidiabetic medications.
The overall neuritic plaque rating, the rating in the entorhinal cortex and amygdala, and the neuritic plaque count in all regions examined differed significantly among the groups. In all of the analyses, the combined medication group had fewer neuritic plaques than did the other groups.
By contrast, the authors found no significant difference in neurofibrillary tangles between the groups.
The findings provide “evidence of substantially lower neuritic plaque density in diabetic subjects taking both insulin and hypoglycemic medication consistent with the effects of both on the neurobiology of insulin,” the researchers concluded. “These pathways should be considered as potentially mechanistically important in the etiology of β amyloid–associated neuropathology and deposition of neuritic plaques.”
Neurology. 2008;71(10):750-757.
Antiepileptic Drug Use May Contribute to Bone Loss in Older Men
NEW YORK, September 19 (Reuters Health)—Use of non–enzyme-inducing antiepileptic drugs (AEDs) independently raises the risk of bone loss at the hip in older men, results of a prospective study suggest.
In the September 2 issue of Neurology, Dr. Kristine E. Ensrud, from the Veterans Affairs Medical Center in Minneapolis, and colleagues pointed out, “AED use may be associated with higher rates of bone loss because [the drugs] may have adverse effects on bone metabolism. On the other hand, AED use may be a marker of factors such as poor health ... that are associated with greater rates of bone loss.”
In 4,222 older community-dwelling participants in the Osteoporosis Fractures in Men study, the researchers analyzed use of non–enzyme-inducing and enzyme-inducing AEDs. They also measured subjects’ hip bone mineral density (BMD) at baseline and at an average of 4.6 years later.
Among men who didn’t use AEDs at all, the average rate of decline in total hip BMD per year was -0.35%, compared with -0.46% among enzyme-inducing AED users and -0.53% among non–enzyme-inducing AED users.
The rate of loss per year was -0.60% among men who were taking non–enzyme-inducing AEDs at both examinations, -0.51% among men taking non–enzyme-inducing AEDs at one examination only, and -0.35% among nonusers.
The researchers pointed out that these findings were achieved after adjustment for a myriad of potential confounders not accounted for in past studies, including age, race, health status, baseline BMD, physical activity, smoking, alcohol intake, total calcium intake, diabetes, kidney disease, bisphosphonate or SSRI use, and BMI.
“Our results suggest that non–enzyme-inducing AED use is associated in a graded manner with rates of hip bone loss in older men, with lower rates of loss among nonusers of AEDs, intermediate rates of loss among intermittent users, and high rates of loss among continuous users,” the authors wrote.
They added, “These findings are supported by prior studies reporting higher fracture rates among non–enzyme-inducing AED users compared with nonusers of AEDs or a similar fracture risk between patients taking non–enzyme-inducing AEDs versus those taking enzyme-inducing AEDs.”
In particular, the results suggest that men who take gabapentin have a 1.4- to 1.8-fold higher adjusted rate of bone loss at the hip compared with nonusers of AEDs.
Neurology. 2008;71(10):723-730.
Relatives of Patients With Brain Tumors Seem to Be at Increased Risk
NEW YORK, September 22 (Reuters Health)—By linking a Utah genealogy database to statewide cancer records, researchers have uncovered evidence of a familial contribution to primary brain cancer risk.
“There has been landmark work done previously using the Utah Population Database resource, in discovering hereditary associations and specific genes for breast cancer, colon cancer, and other nonneoplastic diseases,” Dr. Deborah T. Blumenthal told Reuters Health. “We sought to utilize this unique resource to search for familial relationships in primary brain tumors.”
The database includes more than two million persons with up to 10 generations of genealogic data. Dr. Blumenthal, currently at Tel-Aviv Sourasky Medical Center, and Dr. Lisa A. Cannon-Albright, at the University of Utah in Salt Lake City, examined the risk of brain tumors in the relatives of 744 individuals with astrocytoma, 658 patients with glioblastoma, and one patient with both.
According to their report in the September 23 issue of Neurology, significant excess risk exists among first-degree relatives of patients with astrocytoma or glioblastoma, compared with the rate of disease in the general population.
There was also significantly increased risk among second-degree relatives of patients with astrocytoma.
Noting that cancers with a genetic contribution often occur at an earlier age than sporadic cases, the researchers report that first-degree relatives of patients diagnosed before age 20 were at higher risk. Risk was also elevated for family members of cases with astrocytoma diagnosed before age 15.
“These findings, which remained significant beyond first-degree relations, support the hypothesis of familiality—a common gene or group of genes that may predispose individuals to brain tumors,” Dr. Blumenthal said.
“It needs to be stressed that we are still considering a very small minority (less than 5%) of an already small group of patients (less than 20,000/year in the US) who may have a familial risk for being affected with these tumors,” she added. “However, clinicians should be aware of this association and carefully query family history in their patients. If other family members have neurologic symptoms, the threshold for screening them for a brain tumor should be lower.”
Such symptoms, she explained, may include “new, progressive headaches, nausea or vomiting, seizures (which may be motor or sensory phenomenon, or even episodes of odd smells/tastes or déjà vu, when the temporal lobe is involved), changes in vision, changes in speech or language ability (word-finding difficulty), changes in personality (including apathy or apparent depression), and imbalance or incoordination.”