Low Dose Lithium Treatment of Behavioral Complications in Alzheimer's Disease: Lit-AD Randomized Clinical Trial.

BACKGROUND: A case series suggested efficacy for lithium to treat agitation in dementia, but no placebo-controlled trials have been conducted. OBJECTIVES: To evaluate low-dose lithium treatment of agitation in Alzheimer's disease (AD). METHOD: In a four-site trial, patients with AD and agitation/aggression score ≥4 on the Neuropsychiatric Inventory (NPI) were randomized, double-blind, to lithium carbonate 150-600 mg daily or placebo for 12 weeks. Primary efficacy outcome was change in NPI agitation/aggression; secondary efficacy outcome was treatment response (30% reduction in NPI score for agitation/aggression plus psychosis and a Clinical Global Impression (CGI) score of much or very much improved). Safety profile of lithium was assessed. RESULTS: Fifty-eight of 77 patients (75.3%) completed the trial. In linear mixed effects model analyses, lithium was not significantly superior to placebo for agitation/aggression. Proportion of responders was 31.6% on lithium and 17.9% on placebo (χ2=1.26, p = 0.26). Moderate or marked improvement (CGI) was greater on lithium (10/38=36.8%) than placebo (0/39=0%, Fisher's exact test p <0.001). In exploratory analyses, improvement on lithium was greater than placebo on NPI delusions and irritability/lability (p's<0.05). Lithium showed greater reduction than placebo in patients with high Young Mania Rating Scale scores (ß=5.06; 95%CI,1.18 to 8.94, p = 0.01). Oral dose and serum levels demonstrated similar associations with efficacy outcomes. Lithium did not differ significantly from placebo on safety outcomes. CONCLUSIONS: Low-dose lithium was not efficacious in treating agitation but was associated with global clinical improvement and excellent safety. A larger trial may be warranted of likely lithium-responsive behavioral symptoms that overlap with mania.

Phthalate concentrations and dietary exposure from food purchased in New York State.

BACKGROUND: Phthalates have been found in many personal care and industrial products, but have not previously been reported in food purchased in the United States. Phthalates are ubiquitous synthetic compounds and therefore difficult to measure in foods containing trace levels. Phthalates have been associated with endocrine disruption and developmental alteration. OBJECTIVES: Our goals were to report concentrations of phthalates in U.S. food for the first time, specifically, nine phthalates in 72 individual food samples purchased in Albany, New York, and to compare these findings with other countries and estimate dietary phthalate intake. METHODS: A convenience sample of commonly consumed foods was purchased from New York supermarkets. Methods were developed to analyze these foods using gas chromatography-mass spectroscopy. Dietary intakes of phthalates were estimated as the product of the food consumption rate and concentration of phthalates in that food. RESULTS: The range of detection frequency of individual phthalates varied from 6% for dicyclohexyl phthalate (DCHP) to 74% for di-2-ethylhexyl phthalate (DEHP). DEHP concentrations were the highest of the phthalates measured in all foods except beef [where di-n-octyl phthalate (DnOP) was the highest phthalate found], with pork having the highest estimated mean concentration of any food group (mean 300 ng/g; maximum, 1,158 ng/g). Estimated mean adult intakes ranged from 0.004 µg/kg/day for dimethyl phthalate (DMP) to 0.673 µg/kg/day for DEHP. CONCLUSIONS: Phthalates are widely present in U.S. foods. While estimated intakes for individual phthalates in this study were more than an order of magnitude lower than U.S. Environmental Protection Agency reference doses, cumulative exposure to phthalates is of concern and a more representative survey of U.S. foods is indicated.