Ginkgo biloba extract and long-term cognitive decline: a 20-year follow-up population-based study.

BACKGROUND: Numerous studies have looked at the potential benefits of various nootropic drugs such as Ginkgo biloba extract (EGb761®; Tanakan®) and piracetam (Nootropyl®) on age-related cognitive decline often leading to inconclusive results due to small sample sizes or insufficient follow-up duration. The present study assesses the association between intake of EGb761® and cognitive function of elderly adults over a 20-year period. METHODS AND FINDINGS: The data were gathered from the prospective community-based cohort study 'Paquid'. Within the study sample of 3612 non-demented participants aged 65 and over at baseline, three groups were compared: 589 subjects reporting use of EGb761® at at least one of the ten assessment visits, 149 subjects reporting use of piracetam at one of the assessment visits and 2874 subjects not reporting use of either EGb761® or piracetam. Decline on MMSE, verbal fluency and visual memory over the 20-year follow-up was analysed with a multivariate mixed linear effects model. A significant difference in MMSE decline over the 20-year follow-up was observed in the EGb761® and piracetam treatment groups compared to the 'neither treatment' group. These effects were in opposite directions: the EGb761® group declined less rapidly than the 'neither treatment' group, whereas the piracetam group declined more rapidly (ß = -0.6). Regarding verbal fluency and visual memory, no difference was observed between the EGb761® group and the 'neither treatment' group (respectively, ß = 0.21 and ß = -0.03), whereas the piracetam group declined more rapidly (respectively, ß = -1.40 and ß = -0.44). When comparing the EGb761® and piracetam groups directly, a different decline was observed for the three tests (respectively ß = -1.07, ß = -1.61 and ß = -0.41). CONCLUSION: Cognitive decline in a non-demented elderly population was lower in subjects who reported using EGb761® than in those who did not. This effect may be a specific medication effect of EGb761®, since it was not observed for another nootropic medication, piracetam.

Plasma long-chain omega-3 fatty acids and atrophy of the medial temporal lobe.

OBJECTIVE: The long-chain ω-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are potential candidates for interventions to delay Alzheimer disease (AD), but evidence from clinical studies is mixed. We aimed at determining whether plasma levels of EPA or DHA predict atrophy of medial temporal lobe (MTL) gray matter regions in older subjects. METHODS: A total of 281 community dwellers from the Three-City Study, aged 65 years or older, had plasma fatty acid measurements at baseline and underwent MRI examinations at baseline and at 4 years. We studied the association between plasma EPA and DHA and MTL gray matter volume change at 4 years. RESULTS: Higher plasma EPA, but not DHA, was associated with lower gray matter atrophy of the right hippocampal/parahippocampal area and of the right amygdala (p < 0.05, familywise error corrected). Based on a mean right amygdala volume loss of 6.0 mm(3)/y (0.6%), a 1 SD higher plasma EPA (+0.64% of total plasma fatty acids) at baseline was related to a 1.3 mm(3) smaller gray matter loss per year in the right amygdala. Higher atrophy of the right amygdala was associated with greater 4-year decline in semantic memory performances and more depressive symptoms. CONCLUSION: The amygdala, which develops neuropathology in the early stage of AD and is involved in the pathogenesis of depression, may be an important brain structure involved in the association between EPA and cognitive decline and depressive symptoms.

French adults' cognitive performance after daily supplementation with antioxidant vitamins and minerals at nutritional doses: a post hoc analysis of the Supplementation in Vitamins and Mineral Antioxidants (SU.VI.MAX) trial.

BACKGROUND: Antioxidant properties of some vitamins and trace elements may help to prevent cognitive decline. OBJECTIVE: The aim of the current study was to estimate the long-term effects of antioxidant nutrient supplementation on the cognitive performance of participants in the Supplementation in Vitamins and Mineral Antioxidants (SU.VI.MAX) study 6 y after the end of the trial. DESIGN: This study included 4447 French participants aged 45-60 y who were enrolled in the SU.VI.MAX study (1994-2002), which was a double-blind, placebo-controlled, randomized trial. From 1994 to 2002, participants received daily vitamin C (120 mg), ß-carotene (6 mg), vitamin E (30 mg), selenium (100 µg), and zinc (20 mg) in combination or as a placebo. In 2007-2009, the cognitive performance of participants was assessed with 4 neuropsychological tests (6 tasks). Principal components analysis (PCA) was performed to identify cognitive-function summary scores. Associations between antioxidant supplementation and cognitive functions, in the full sample and by subgroups, were estimated through ANOVA and expressed as mean differences and 95% CIs. Subgroup analyses were performed according to baseline characteristics. RESULTS: Subjects receiving active antioxidant supplementation had better episodic memory scores (mean difference: 0.61; 95% CI: 0.02, 1.20). PCA indicated 2 factors that were interpreted as showing verbal memory and executive functioning. Verbal memory was improved by antioxidant supplementation only in subjects who were nonsmokers or who had low serum vitamin C concentrations at baseline. CONCLUSION: This study supports the role of an adequate antioxidant nutrient status in the preservation of verbal memory under certain conditions. This trial was registered at clinicaltrials.gov as NCT00272428.

Adherence to nutritional recommendations and subsequent cognitive performance: findings from the prospective Supplementation with Antioxidant Vitamins and Minerals 2 (SU.VI.MAX 2) study.

BACKGROUND: Few studies have investigated the long-term effect of overall nutritional recommendations on cognition. OBJECTIVE: In a French cohort of middle-aged adults, we evaluated the association between the French National Nutrition and Health Program (Program National Nutrition Santé) Guideline Score (PNNS-GS) assessed at baseline and cognitive performance evaluated 13 y later. DESIGN: The PNNS-GS was estimated at baseline (1994-1996) (maximum score: 15 points) in 2135 subjects in the SU.VI.MAX (Supplementation with Antioxidant Vitamins and Minerals) study. We assessed cognitive performance of subjects in 2007-2009 via a battery of 4 neuropsychologic tests that included phonemic and semantic fluency, the RI-48 (rappel indicé-48 item) cued-recall test, the trail-making test, and forward and backward digit spans. A principal components analysis was performed to account for correlations in test scores. Multivariate linear regression models or analyses of covariance were also performed. RESULTS: In a multivariate model, we observed a positive association between the PNNS-GS and the cued-recall test and semantic and phonemic fluency tasks, whereas no association was observed with digit spans. The principal components analysis revealed 2 factors interpreted as reflecting verbal memory and executive functioning. Better adherence to nutritional recommendations was significantly associated with the verbal memory factor (ß = 0.41; 95% CI: 0.17, 0.64), whereas no association was shown with the executive functioning factor. Removing specific components from the PNNS-GS did not modify the findings. CONCLUSION: This study suggests that strong compliance with nutritional recommendations in midlife is associated in elderly individuals with better verbal memory, which is a cognitive domain that is particularly vulnerable to pathologic aging and Alzheimer disease. This trial was registered at clinicaltrials.gov as NCT00272428.

Deep brain stimulation of the ventral caudate nucleus in the treatment of obsessive-compulsive disorder and major depression. Case report.

Obsessive-compulsive disorder (OCD) is an anxiety disorder associated with recurrent intrusive thoughts and repetitive behaviors. Although conventional pharmacological and/or psychological treatments are well established and effective in treating OCD, symptoms remain unchanged in up to 30% of patients. Deep brain stimulation (DBS) of the anterior limb of the internal capsule has recently been proposed as a possible therapeutic alternative in treatment-resistant OCD. In the present study, the authors tested the hypothesis that DBS of the ventral caudate nucleus might be effective in a patient with intractable severe OCD and concomitant major depression. Psychiatric assessment included the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), the Hamilton Depression Rating Scale (HDRS), the Hamilton Anxiety Rating Scale (HARS), and the Global Assessment of Functioning (GAF) Scale for determining the symptom severity of OCD, depression, and anxiety as well as the quality of pychosocial and occupational functioning, respectively. Neuropsychological assessment consisted of a wide range of tests primarily exploring memory and executive functions. Deep brain stimulation of the ventral caudate nucleus markedly improved symptoms of depression and anxiety until their remission, which was achieved at 6 months after the start of stimulation (HDRS < or = 7 and HARS < or = 10). Remission of OCD (Y-BOCS < 16) was also delayed after 12 or 15 months of DBS. The level of functioning pursuant to the GAF scale progressively increased during the 15-month follow-up period. No neuropsychological deterioration was observed, indicating that DBS of the ventral caudate nucleus could be a promising strategy in the treatment of refractory cases of both OCD and major depression.