BACKGROUND: It is colloquially considered that cognitive tests can be adversely affected by administration in a foreign location. However, a definitive demonstration of this is lacking in the literature. To determine whether or not this is the case, we compared the results of cognitive testing in a familiar versus foreign environment by single test administrator of individuals diagnosed with Alzheimer's disease randomized to placebo in a multi-site clinical study. FINDINGS: Cognitive tests were administered to 6 long-term residents of an assisted living facility at their residence (the "Familiar" cohort). The identical tests were administered to a newly admitted resident and to 2 community-dwelling individuals who drove to the administrator's office for the first time (the "Foreign" cohort). Secondary testing was administered 3 months later at the same respective locations. Caregivers of participants completed reports of mood, behavior and activities of daily living. The Familiar cohort performed equally well at both visits. The Foreign cohort performed significantly worse than the Familiar cohort at baseline. They improved statistically, and matched Familiar cohort performance, by their second visit. Caregiver reports for both cohorts were unchanged between visits. CONCLUSIONS: These findings support the notion that a foreign location can adversely affect performance on cognitive tests, and therefore support cognitive testing in a familiar location.

Background: It is increasingly recognized that interventions for dementia must shift towards prevention to obtain maximal efficacy and any significant degree of disease modification. Nutritional supplementation with single agents has shown varied results, suggesting the need for combinatorial intervention. Methods: We conducted a 3-month, randomized, multi-site, phase II study in which 141 individuals diagnosed with Alzheimer’s disease (AD) and 34 individuals with Mild Cognitive Impairment received a nutraceutical formulation (NF; folate, alpha-tocopherol, B12, S-adenosyl methioinine, N-acetyl cysteine, acetyl-L-carnitine) or indistinguishable placebo under double-blind conditions, followed by an open-label extension in which all individuals received NF for a total of 1yr. An additional 38 individuals with AD received NF under open-label conditions from baseline for 1yr. The primary outcome was defined as cognitive performance. Secondary outcomes were defined as behavioral and psychological symptoms of dementia and activities of daily living. Results: Participants randomized to NF improved statistically within 3 months in cognitive performance as ascertained by Clox-1 and the Dementia Rating Scale, and their caregivers reported improvement in Neuropsychiatric Inventory. Participants receiving NF either continued to improve or maintained their baseline performance during open-label extensions. Participants randomized to placebo did not improve, but during open-label extensions displayed similar improvement within 3 months to that of participants initially randomized to NF. Caregivers reported no change in Activities of Daily Living for either cohort. Conclusions: These findings confirm and extend prior phase I studies in which NF improved or maintained cognitive performance and behavioral symptoms for individuals with AD, and improved cognitive performance for community-dwelling individuals without dementia. In published studies with transgenic mice NF reduced PS-1 expression, beta and gamma secretase activity, Abeta deposits, phospho-tau, homocysteine and oxidative damage, and increased acetylcholine and glutathione. This comprehensive impact of NF on AD-related neuropathology supports the possibility that NF may harbor disease-modifying properties.