Protocol for Project FACT: a randomised controlled trial on the effect of a walking program and vitamin B supplementation on the rate of cognitive decline and psychosocial wellbeing in older adults with mild cognitive impairment [ISRCTN19227688]

BACKGROUND: the prevalence of individuals with cognitive decline is increasing since the number of elderly adults is growing considerably. The literature provides promising results on the beneficial effect of exercise and vitamin supplementation on cognitive function both in cognitively healthy as well as in the demented elderly. METHODS/DESIGN: the design is a two-by-two factorial randomised controlled trial. The study population consists of independently living elderly, between 70 and 80 years old, with mild cognitive impairment (MCI). In the RCT the effect of two interventions, a walking program and vitamin supplementation, is examined. The walking program (WP) is a group-based program aimed at improving cardiovascular endurance; frequency two lessons a week; lesson duration one hour; program duration one year. Non-walking groups receive a placebo activity program (PAP) (i.e. low intensive non-aerobic group exercises, like stretching) with the same frequency, lesson and program duration. Vitamin supplementation consists of a single daily vitamin supplement containing 50 mg B6, 5 mg folic acid and 0,4 mg B12 for one year. Subjects not receiving vitamin supplements are daily taking an identically looking placebo pill, also for a year. Participants are randomised to four groups 1) WP and vitamin supplements; 2) WP and placebo supplements; 3) PAP and vitamin supplements; 4) PAP and placebo supplements. Primary outcome measures are measures of cognitive function. Secondary outcomes include psychosocial wellbeing, physical activity, cardiovascular endurance and blood vitamin levels. DISCUSSION: no large intervention study has been conducted yet on the effect of physical activity and vitamin supplementation in a population-based sample of adults with MCI. The objective of the present article is to describe the design of a randomised controlled trial examining the effect of a walking program and vitamin B supplementation on the rate of cognitive decline in older adults with MCI

Deletion of CB2 cannabinoid receptor induces schizophrenia-related behaviors in mice

The possible role of the CB2 receptor (CB2 r) in psychiatric disorders has been considered. Several animal models use knockout (KO) mice that display schizophrenia-like behaviors and this study evaluated the role of CB 2 r in the regulation of such behaviors. Mice lacking the CB 2 r (CB2 KO) were challenged in open field, light-dark box, elevated plus-maze, tail suspension, step down inhibitory avoidance, and pre-pulse inhibition tests (PPI). Furthermore, the effects of treatment with cocaine and risperidone were evaluated using the OF and the PPI test. Gene expression of dopamine D2 (D2 r), adrenergic-α 2C (α 2C r), serotonergic 5-HT 2A and 5-HT 2C receptors (5-HT 2A r and 5-HT 2C r) were studied by RT-PCR in brain regions related to schizophrenia. Deletion of CB 2 r decreased motor activity in the OF test, but enhanced response to acute cocaine and produced mood-related alterations, PPI deficit, and cognitive impairment. Chronic treatment with risperidone tended to impair PPI in WT mice, whereas it normalized the PPI deficit in CB2 KO mice. CB2 KO mice presented increased D2 r and α 2C r gene expressions in the prefrontal cortex (PFC) and locus coeruleus (LC), decreased 5-HT 2C r gene expression in the dorsal raphe (DR), and 5-HT 2A r gene expression in the PFC. Chronic risperidone treatment in WT mice left α 2C r gene expression unchanged, decreased D2 r gene expression (15 g/kg), and decreased 5-HT 2C r and 5-HT 2A r in PFC and DR. In CB2 KO, the gene expression of D2 r in the PFC, of α 2C r in the LC, and of 5-HT 2C r and 5-HT 2Ar in PFC was reduced; 5-HT 2C r and 5-HT 2A r gene expressions in DR were increased after treatment with risperidone. These results suggest that deletion of CB2 r has a relation with schizophrenia-like behaviors. Pharmacological manipulation of CB2 r may merit further study as a potential therapeutic target for the treatment of schizophrenia-related disorders. © 2011 American College of Neuropsychopharmacology. All rights reserved.This research was supported by grants from the Ministry of Science and Innovation (SAF 2008-01106) and Ministry of Health (RETICS RD06/0001/1004 and PNSD 2007/061) to JM. AOA is a postdoctoral fellow of ‘Fundación para la Investigación Sanitaria en Castilla La Mancha’ (FISCAM).Peer Reviewe