Long-term NSAID use protects against Alzheimer’s disease, with the strongest findings associated with ibuprofen, researchers reported in the May 6 Neurology. Veterans 55 and older with incident Alzheimer’s disease were matched with controls and categorized by NSAID exposure in yearly increments from no use to more than five years of use. The odds ratio (OR) for Alzheimer’s disease among NSAID users decreased from 0.98 for up to one year of use to 0.76 for longer than five years of use, compared to those with no NSAID use. For those who used ibuprofen, the OR decreased from 1.03 to 0.56. “Effects of other NSAID classes and individual NSAIDs were inconsistent,” the researchers noted.

Risk factors for cognitive impairment and dementia differ between men and women, according to research in the online May 1 Journal of Neurology, Neurosurgery, and Psychiatry. In a four-year follow-up study of 6,892 subjects 65 and older, 42% had mild cognitive impairment (MCI) at baseline, and men and women with MCI were more likely to have depression symptoms and be taking anticholinergic drugs. Men were more likely to have a higher BMI, diabetes, and stroke. Women were more likely to have poor subjective health, be disabled, be socially isolated, and have insomnia. Principal adjusted risk factors for men for progression from MCI to dementia in descending order were APOE ε4 allele, stroke, low level of education, loss of instrumental activities of daily living (IADL), and age. For women, risk factors in descending order were IADL loss, APOE ε4 allele, low level of education, subclinical depression, use of anticholinergic drugs, and age.

Green tea catechin polyphenols (GTPs) attenuated intermittent hypoxia–induced spatial learning deficits and mitigated intermittent hypoxia–induced oxidative stress through beneficial effects on oxidant pathways, according to a study in the May 15 American Journal of Respiratory and Critical Care Medicine. In Sprague-Dawley rats during the Morris water maze probe trials, GTPs prevented intermittent hypoxia–induced decreases in spatial bias for the hidden platform as well as increases in p47phox expression within the hippocampal CA1 region. In comparison to room-air control animals, rats not given GTPs experienced a doubling of their cortical malondialdehyde levels, while GTP-treated rats showed a 40% reduction in malondialdehyde levels. Increases in brain receptor for advanced glycation end products and glial fibrillary acidic protein expression were attenuated in animals treated with GTP.

Multiple sclerosis (MS) in children is associated with cognitive impairment and low IQ scores, according to a report in the May 13 Neurology. Of the 63 patients assessed with a battery of 17 tests, five (8%) exhibited an IQ below 70, 19 (31%) met criteria for cognitive impairment, and 32 (53%) failed at least two tests. Patients with MS also had trouble with linguistic abilities. “In the regression analysis, the only significant predictor of cognitive impairment was an IQ score lower than 90 (odds ratio [OR], 18.2),” the researchers stated. Another significant predictor was younger age at onset (OR, 0.7). Depressive symptoms (6%), fatigue (73%), and a negative effect of MS on school and everyday activities (56%) were also reported.

A mutant gene has been linked to epilepsy and mental retardation limited to females (EFMR), according to a study in the online May 11 Nature Genetics. Researchers systematically resequenced 737 X chromosome genes in seven families with EFMR and revealed different protocadherin 19 (PCDH19) gene mutations. Five mutations resulted in the introduction of a premature termination codon, two of which revealed nonsense-mediated decay of PCDH19 mRNA and affected adhesiveness of PCDH19 through impaired calcium binding. PCDH19 is the first member of the cadherin superfamily to be directly implicated in epilepsy or mental retardation.

Astem cell population that produces neurons affecting learning and memory was identified in the adult hippocampus, reported researchers in the May 14 Journal of Neuroscience. A study of the adult mouse hippocampus found that depolarizing levels of KCI produced a threefold increase in the number of neurospheres generated. Depolarizing levels of KCI also led to the emergence of a small subpopulation of precursors (approximately eight per hippocampus) with the capacity to generate very large neurospheres (> 250 μm in diameter). Properties of stem cells such as multipotentiality and self-renewal were observed in these contained cells. Conversely, the same conditions in the subventricular zone decreased neurosphere numbers by approximately 40%. “The latent hippocampal progenitor population can be activated in vivo in response to prolonged neural activity found in status epilepticus,” the study authors commented.

Strattera (atomoxetine HCl), a selective norepinephrine reuptake inhibitor, has received FDA approval for maintenance treatment of ADHD in children and adolescents. The approval follows an 18-month trial that included about 600 patients ages 6 to 15 who met DSM-IV criteria for ADHD. Atomoxetine HCl was superior to placebo in maintaining continuous efficacy in patients throughout the study, as measured by the ADHD Rating Scale; patients taking atomoxetine HCl also had a lower relapse rate by the end of the trial compared with those taking placebo (2.5% vs 12.2%). Common side effects in children were upset stomach, decreased appetite, nausea or vomiting, tiredness, and drowsiness. Prior studies have also found that atomoxetine HCl increases the risk of suicidal thoughts in some children and teens.

The Dietary Approaches to Stop Hypertension (DASH) diet lowered risk of coronary heart disease and stroke among middle-aged women, according to research in the April 14 Archives of Internal Medicine. Diet was assessed seven times in a 24-year follow-up period with the use of validated food frequency questionnaires. Among 88,517 female nurses ages 34 to 59 without history of cardiovascular disease or diabetes at baseline, 2,129 subjects experienced incident nonfatal myocardial infarction, 976 died from coronary heart disease, and 3,105 had strokes. The magnitude of risk difference was similar for nonfatal myocardial infarction and fatal coronary heart disease. Blood samples revealed that the DASH score was significantly associated with lower plasma levels of C-reactive protein and interleukin 6.

Treatment with fibroblast growth factor 2 (FGF-2) may enhance the growth of new neurons in patients with Parkinson’s disease, according to a study in the May 15 Neuroscience. Researchers observed mice given the parkinsonian toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) that causes degeneration of nigrostriatal dopamine neurons and found that “MPTP lesions increased the incorporation of 5-bromo-2´-deoxyuridine-5´-monophosphate (BrdU), as well as the number of cells that co-expressed BrdU and the immature neuronal marker doublecortin (DCX), in two neuroproliferative regions—the subgranular zone of the dentate gyrus and the rostral subventricular zone.” These cells were found in increased numbers in the striatum but not in the substantia nigra. FGF-2 increased the number of BrdU/DCX-immunopositive cells in the substantia nigra.

Gene therapy can combat late infantile neuronal ceroid lipofuscinosis (LINCL), according to a study in the online May 12 Human Gene Therapy. Researchers administered a total average dose of 2.5 x 10¹² particle units of an adeno-associated virus serotype 2 vector expressing the human CLN2 cDNA to 12 locations in the CNS of 10 children with LINCL. During an 18-month period, rates of decline of all MRI parameters were slower in treated as opposed to nontreated patients, although the numbers were not statistically significant. The neurologic rating scale showed a significantly reduced rate of decline for treated patients. No unexpected serious adverse effects were unequivocally attributable to the vector; however, one subject died 49 days postsurgery after developing status epilepticus on day 14, but with no evidence of CNS inflammation. Four subjects developed a mild, mostly transient, humoral response to the vector.

Women who are currently taking hormone therapy have an increased risk of stroke, researchers reported in the April 28 Archives of Internal Medicine. The increased risk was found in women initiating hormone therapy at young ages or near menopause and at older ages or more than 10 years after menopause. Less than five years of hormone therapy initiated at younger ages was not associated with a clear increase in stroke; however, this may be due to a small number of cases. Risk in women ages 50 through 54 indicated approximately two additional cases of stroke per 10,000 women per year taking hormones. Dose of oral conjugated estrogen and stroke had relative risks of 0.93, 1.54, and 1.62 for doses of 0.3, 0.625, and 1.25 mg, respectively.

NR