Neurology July 2009 Volume 73 Issue 3

Objective: To develop a late-life dementia risk index that can accurately stratify older adults into those with a low, moderate, or high risk of developing dementia within 6 years.Methods: Subjects were 3,375 participants in the Cardiovascular Health Cognition Study without evidence of dementia at baseline. We used logistic regression to identify those factors most predictive of developing incident dementia within 6 years and developed a point system based on the logistic regression coefficients.Results: Subjects had a mean age of 76 years at baseline; 59% were women and 15% were African American. Fourteen percent (n = 480) developed dementia within 6 years. The final late-life dementia risk index included older age (1-2 points), poor cognitive test performance (2-4 points), body mass index <18.5 (2 points), >=1 apolipoprotein E [varepsilon]4 alleles (1 point), cerebral MRI findings of white matter disease (1 point) or ventricular enlargement (1 point), internal carotid artery thickening on ultrasound (1 point), history of bypass surgery (1 point), slow physical performance (1 point), and lack of alcohol consumption (1 point) (c statistic, 0.81; 95% confidence interval, 0.79-0.83). Four percent of subjects with low scores developed dementia over 6 years compared with 23% of subjects with moderate scores and 56% of subjects with high scores.Conclusions: The late-life dementia risk index accurately stratified older adults into those with low, moderate, and high risk of developing dementia. This tool could be used in clinical or research settings to target prevention and intervention strategies toward high-risk individuals.(C)2009AAN Enterprises, Inc.

Objective: To explore factors throughout the lifespan that influence cognition in midlife to late life.Methods: We conducted a retrospective birth cohort study of 2,062 individuals born during 1921-1954 in Beijing, China. In 2003-2005, birth records were abstracted, and participants then 50-82 years old received standardized examinations for health, cognition, and socio-environmental measures. Using cumulative logit models, we assessed adjusted relative effects of prenatal, early life, and adult factors on mid- to late-life cognition.Results: Most prenatal factors were associated with mid- to late-life cognition in the unadjusted models. However, when childhood and adult factors were sequentially added to the models, the impact of prenatal factors showed successive attenuation in effect size, and became insignificant. In contrast, early life factors remained significantly associated with mid- to late-life cognition even after full life-course adjustments. Specifically, those whose fathers had laborer vs professional occupations (odds ratio [OR]Laborer 1.74; 95% confidence interval [CI]: 1.25-2.42) had poorer cognitive outcomes, while individuals who drank milk daily in childhood (OR 0.65; 95% CI: 0.54-0.80), had more years of education (OR10-12 years 0.60; 95% CI: 0.45-0.81; OR13+ yrs 0.29; 95% CI: 0.23-0.38), and were taller adults (ORheight >= SD 0.65; 95% CI: 0.49-0.86) had better cognition. The high prenatal risk infants had similar patterns with a trend toward a stronger association between cognition and socioenvironmental factors.Conclusion: Mid- to late-life cognition is influenced by factors over the entire lifespan with the greatest impact coming from early life exposures. Nutrition, education, social, and family environment in early life may have a long-term impact on cognition in developing countries.(C)2009AAN Enterprises, Inc.

Background: Superficial siderosis is a rare radiologic diagnosis of hemosiderin deposition in subpial brain layers. In case studies, an association between superficial siderosis and cerebral amyloid angiopathy (CAA) has been described. Also, a potential role of superficial siderosis in Alzheimer disease (AD) was hypothesized. All previously reported cases of superficial siderosis were detected because of overt clinical symptoms. We studied the occurrence of superficial siderosis on brain MRI in a general population of nondemented elderly.Methods: In 1,062 persons (mean age 69.6 years) from the population-based Rotterdam Scan Study, we performed T2*-weighted MRI to assess the presence of superficial siderosis. Furthermore, the presence, number, and location of cerebral microbleeds were rated, as lobar microbleeds are thought to be indicative of CAA.Results: We found that superficial siderosis was present in 7 (0.7%) individuals, all of whom had cerebral microbleeds in lobar locations. Furthermore, in all 7 persons, microbleeds were located in close vicinity to superficial siderosis.Conclusions: Our results provide further indirect support for the presumed link between superficial siderosis and cerebral amyloid angiopathy (CAA). Whether superficial siderosis may be a marker for severity or worse prognosis of CAA needs to be further evaluated in longitudinal follow-up.(C)2009AAN Enterprises, Inc.

Background: In September 2007, shortages of generic selegiline occurred, forcing patients to either switch to more expensive alternatives or forego treatment. We sought to evaluate prescription trends of generic selegiline and to quantify the economic impact of any resulting drug substitution of more expensive alternatives.Methods: We analyzed proprietary data from IMS Health on monthly prescriptions in the United States for selegiline and potential substitutes from February 2002 through December 2007. Linear regression was used to predict the number of expected prescriptions after August 2007 had a shortage not occurred. The main outcome measures were the changes in prescriptions filled and the economic impact of drug substitution.Results: Prior to the shortage, total prescriptions filled for generic selegiline decreased 42%, and supply consolidated into one company, Apotex Inc., Toronto, Canada, whose market share increased from 41% to 83%. During the first 4 months of the shortage, Apotex Inc. filled 10,500 fewer prescriptions than projected and other selegiline manufacturers filled 7,400 more than projected for a net shortage of 3,100 prescriptions. The number of branded selegiline capsules filled during this period increased by 1,800 above projections, and 1,300 prescriptions for generic selegiline were not refilled or substituted. The societal cost of substituting generic selegiline with branded capsules was $75,000 over the first 4 months of the shortage.Conclusions: Generic drug shortages carry economic and health implications. Given ongoing consolidation in the generics drug industry, these shortages may become more common and may require heightened regulatory scrutiny of the generic drug industry.(C)2009AAN Enterprises, Inc.

Objective: The temporal distribution of seizures in women with localization-related epilepsy occurs periodically according to a model "clock" with the peak phase of occurrence corresponding to menstrual onset. The location and laterality of the epileptic lesion as well as patient age may affect periodicity.Methods: Baseline data from seizure and menstrual diaries of ~3 months duration were obtained from 100 women enrolled in a trial of hormonal therapy for localization-related epilepsy. Durations of individual cycles were normalized to a common menstrual phase and period. Normalized data were then combined to create distributions evaluated by localization (lobar: temporal [TL], extratemporal [XL], multifocal [MF], unknown), lateralization (left, right, bilateral, unknown), and age. Distributions were evaluated with analysis of variance (ANOVA) and curve-fitted by nonlinear least squares cosinor analysis.Results: A total of 71 patients had TL (left = 25, right = 29, bilateral = 17), 10 XL, 14 MF, and 5 unknown seizure foci. XL and MF seizures occurred randomly across the 28-day cycle. TL seizures (left = 875, right = 706) occurred nonrandomly (ANOVA p = 0.0003) and cyclically with peak occurrence near onset of menses ([value +/- SD] peak = 1.6 +/- 2.3 days, period = 27.0 days). Left-side TL seizures peaked cyclically at onset of menses (ANOVA p = 0.04, peak = 0.0 +/- 3.0 days, period = 30 days); right-side TL seizures occurred randomly. Age did not have a cyclical effect. Women below the median age had a significantly higher seizure rate than those above the median age.Conclusion: Circalunar rhythms of seizures in women, and therefore, possibly strategies of hormonal treatments of catamenial epilepsy, vary with the neuroanatomic substrate of the seizure focus.(C)2009AAN Enterprises, Inc.