Jennifer A. Emond

Docosahexaenoic acid supplementation and cognitive decline in Alzheimer disease: A randomized trial

CONTEXT Docosahexaenoic acid (DHA) is the most abundant long-chain polyunsaturated fatty acid in the brain. Epidemiological studies suggest that consumption of DHA is associated with a reduced incidence of Alzheimer disease. Animal studies demonstrate that oral intake of DHA reduces Alzheimer-like brain pathology. OBJECTIVE To determine if supplementation with DHA slows cognitive and functional decline in individuals with Alzheimer disease. DESIGN, SETTING, AND PATIENTS A randomized, double-blind, placebo-controlled trial of DHA supplementation in individuals with mild to moderate Alzheimer disease (Mini-Mental State Examination scores, 14-26) was conducted between November 2007 and May 2009 at 51 US clinical research sites of the Alzheimers Disease Cooperative Study. INTERVENTION Participants were randomly assigned to algal DHA at a dose of 2 g/d or to identical placebo (60% were assigned to DHA and 40% were assigned to placebo). Duration of treatment was 18 months. MAIN OUTCOME MEASURES Change in the cognitive subscale of the Alzheimers Disease Assessment Scale (ADAS-cog) and change in the Clinical Dementia Rating (CDR) sum of boxes. Rate of brain atrophy was also determined by volumetric magnetic resonance imaging in a subsample of participants (n = 102). RESULTS A total of 402 individuals were randomized and a total of 295 participants completed the trial while taking study medication (DHA: 171; placebo: 124). Supplementation with DHA had no beneficial effect on rate of change on ADAS-cog score, which increased by a mean of 7.98 points (95% confidence interval [CI], 6.51-9.45 points) for the DHA group during 18 months vs 8.27 points (95% CI, 6.72-9.82 points) for the placebo group (linear mixed-effects model: P = .41). The CDR sum of boxes score increased by 2.87 points (95% CI, 2.44-3.30 points) for the DHA group during 18 months compared with 2.93 points (95% CI, 2.44-3.42 points) for the placebo group (linear mixed-effects model: P = .68). In the subpopulation of participants (DHA: 53; placebo: 49), the rate of brain atrophy was not affected by treatment with DHA. Individuals in the DHA group had a mean decline in total brain volume of 24.7 cm(3) (95% CI, 21.4-28.0 cm(3)) during 18 months and a 1.32% (95% CI, 1.14%-1.50%) volume decline per year compared with 24.0 cm(3) (95% CI, 20-28 cm(3)) for the placebo group during 18 months and a 1.29% (95% CI, 1.07%-1.51%) volume decline per year (P = .79). CONCLUSION Supplementation with DHA compared with placebo did not slow the rate of cognitive and functional decline in patients with mild to moderate Alzheimer disease. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00440050.

Physical activity, diet, adiposity and female breast cancer prognosis: A review of the epidemiologic literature

Given the increasing numbers of long-term survivors of breast cancer, research specific to prevention of recurrence, new breast cancer events, and mortality is of considerable public health importance. The objective of this report is to present a review of the published epidemiologic research on lifestyle and breast cancer outcomes among women with a history of breast cancer. This review focused on physical activity, diet, and adiposity; and the primary outcomes were additional breast cancer events and mortality. The most consistent finding from observational studies was that adiposity was associated with a 30% increased risk of mortality. Although the observational data were not as consistent (or abundant), physical activity appeared to be associated with a 30% decreased risk of mortality. These data do not indicate that alcoholic drinks are a risk factor. Based only on the observational studies, total dietary fat appeared to be a risk factor, fiber was protective, and information on micronutrients and specific foods was sparse. However, the null results of 2 dietary intervention trials in survivors suggests that lowering fat intake or increasing consumption of fruits, vegetables, and fiber will not lead to improved prognosis in breast cancer survivors. Given that a high proportion of breast cancer patients appear to be both sedentary and obese/overweight, clinical trials are needed to investigate whether the combination of increased physical activity and reduced adiposity can improve breast cancer prognosis.

Incidence of New-Onset Seizures in Mild to Moderate Alzheimer Disease

OBJECTIVE To estimate the incidence rate and predictors of seizures in patients with mild to moderate Alzheimer disease (AD). DESIGN Cohort study of patients with mild to moderate AD in clinical trials. Risk factors for potential seizures were evaluated by stratified descriptive statistics and univariable and multivariable Cox proportional hazards regressions. SETTING Pooled patient-level data from 10 Alzheimer Disease Cooperative Study clinical trials in mild to moderate AD from 1995 to 2010. PATIENTS Three thousand seventy-eight subjects randomized to the treatment or placebo arms of 10 AD clinical trials. Screening Mini-Mental State Examination scores ranged between 10 and 28. RESULTS Eighteen seizures were reported in 3078 randomized subjects, with an incidence rate of 484 per 100 000 person-years (95% CI, 287-764). Statistically significant independent risk factors for seizure were younger age (adjusted hazard ratio, 0.80; 95% CI, 0.69-0.93 per every 5 years of age), greater cognitive impairment at baseline (adjusted hazard ratio, 2.79; 95% CI, 1.06-7.33 for Mini-Mental State Examination scores <18 compared with Mini-Mental State Examination scores ≥18), and antipsychotic use at baseline (adjusted hazard ratio, 3.47; 95% CI, 1.33-9.08). CONCLUSIONS Seizure rates in patients with mild to moderate AD in clinical trials are similar to rates observed in longer observational cohort studies, but they are greater than expected in the general elderly population. Younger age, greater degree of cognitive impairment, and history of antipsychotic use were independent risk factors for new-onset seizures in AD.

Dietary Pattern Influences Breast Cancer Prognosis in Women Without Hot Flashes: The Women's Healthy Eating and Living Trial

PURPOSE To determine whether a low-fat diet high in vegetables, fruit, and fiber differentially affects prognosis in breast cancer survivors with hot flashes (HF) or without HF after treatment. PATIENTS AND METHODS A secondary analysis was conducted on 2,967 breast cancer survivors, age 18 to 70 years, who were randomly assigned between 1995 and 2000 in a multicenter, controlled trial of a dietary intervention to prevent additional breast cancer events and observed through June 1, 2006. We compared the dietary intervention group with a group who received five-a-day dietary guidelines. RESULTS Independent of HF status, a substantial between-group difference among those who did and did not receive dietary guidelines was achieved and maintained at 4 years in intake of vegetable/fruit servings per day (54% higher; 10 v 6.5 servings/d, respectively), fiber (31% higher; 25.5 v 19.4 g/d, respectively), and percent energy from fat (14% lower; 26.9% v 31.3%, respectively). Adjusting for tumor characteristics and antiestrogen treatment, HF-negative women assigned to the intervention had 31% fewer events than HF-negative women assigned to the comparison group (hazard ratio [HR] = 0.69; 95% CI, 0.51 to 0.93; P = .02). The intervention did not affect prognosis in the women with baseline HFs. Furthermore, compared with HF-negative women assigned to the comparison group, HF-positive women had significantly fewer events in both the intervention (HR = 0.77; 95% CI, 0.59 to 1.00; P = .05) and comparison groups (HR = 0.65; 95% CI, 0.49 to 0.85; P = .002). CONCLUSION A diet with higher vegetable, fruit, and fiber and lower fat intakes than the five-a-day diet may reduce risk of additional events in HF-negative breast cancer survivors. This suggestive finding needs confirmation in a trial in which it is the primary hypothesis.

Weight Loss Is Associated With Increased Serum 25-Hydroxyvitamin D in Overweight or Obese Women

Low circulating concentrations of vitamin D metabolites have been associated with increased risk for several diseases and clinical conditions. Large observational studies and surveys have shown that obesity is independently associated with lower serum 25‐hydroxyvitamin D (25(OH)D) concentration. Few studies have examined the effect of weight loss on serum 25(OH)D concentration. The purpose of this study was to prospectively examine the effect of weight loss on serum 25(OH)D concentration. Data were collected from 383 overweight or obese women who participated in a 2‐year clinical trial of a weight‐loss program, in which 51% (N = 195) lost at least 5% of baseline weight by 24 months, 18% (N = 67) lost 5–10%, and 33% (N = 128) lost >10%. Women who did not lose weight at 24 months had an increase in serum 25(OH)D of 1.9 (9.7) ng/ml (mean (SD)); 25(OH)D increased by 2.7 (9.1) ng/ml for those who lost 5–10% of baseline weight; and 25(OH)D increased by 5.0 (9.2) ng/ml for those who lost >10% of baseline weight (P = 0.014). At baseline, 51% (N = 197) of participants met or exceeded the recommended serum concentration of 20 ng/ml. By study end, 64% (N = 230) of overweight or obese women met this goal, as well as 83% (N = 20) of those whose weight loss achieved a normal BMI. These findings suggest that weight loss, presumably associated with a reduction in body fat, is associated with increased serum 25(OH)D concentration in overweight or obese women.

Influence of apolipoprotein E ɛ4 on rates of cognitive and functional decline in mild cognitive impairment

Apolipoprotein E ɛ4 (APOE ɛ4) allele carrier status has been well established as a risk factor for developing Alzheimers disease. However, the specific influence of APOE ɛ4 allele status on cognitive and functional rates of decline in mild cognitive impairment (MCI) is poorly understood. We examine the prospective association of APOE ɛ4 allele status on measures of cognitive and functional decline in subjects with amnestic MCI (aMCI).

Do Latino and non-Latino grocery stores differ in the availability and affordability of healthy food items in a low-income, metropolitan region?

OBJECTIVE To compare non-ethnically based supermarkets and Latino grocery stores (tiendas) in a lower-income region with regard to the availability, quality and cost of several healthy v. unhealthy food items. DESIGN A cross-sectional study conducted by three independent observers to audit twenty-five grocery stores identified as the main source of groceries for 80 % of Latino families enrolled in a childhood obesity study. Stores were classified as supermarkets and tiendas on the basis of key characteristics. SETTING South San Diego County. SUBJECTS Ten tiendas and fifteen supermarkets. RESULTS Tiendas were smaller than supermarkets (five v. twelve aisles, P = 0·003). Availability of fresh produce did not differ by store type; quality differed for one fruit item. Price per unit (pound or piece) was lower in tiendas for most fresh produce. The cost of meeting the US Department of Agricultures recommended weekly servings of produce based on an 8368 kJ (2000 kcal)/d diet was

Short sleep duration is associated with higher energy intake and expenditure among African-American and non-Hispanic white adults.

US 3·00 lower in tiendas compared with supermarkets (P < 0·001). The cost of 1 gallon of skimmed milk was significantly higher in tiendas (

Effect of Postdiagnosis Weight Change on Hot Flash Status Among Early-Stage Breast Cancer Survivors

US 3·29 v.

Adding Delayed Recall to the Alzheimer Disease Assessment Scale is Useful in Studies of Mild Cognitive Impairment But Not Alzheimer Disease

US 2·69; P = 0·005) and lean (7 % fat) ground beef was available in only one tienda (10 %) compared with ten (67 %) supermarkets (P = 0·01). CONCLUSIONS Barriers remain in the ability to purchase healthier dairy and meat options in tiendas; the same is not true for produce. These results highlight the potential that tiendas have in improving access to quality, fresh produce within lower-income communities. However, efforts are needed to increase the access and affordability of healthy dairy and meat products.