Anthropometric measurements collected through WHI follow-up and prior to WHISCA enrollment were available for 98% (2,256) of the sample. examines the distribution of pre-WHISCA weight changes across subgroups defined by a range of risk factors for cognitive decline and dementia. Average weight at WHI enrollment was 74.1 kg with interquartile range 62.6 kg to 82.9 kg. Mean BMI was 28.6 kg/m2, with interquartile range 24.5 to 31.8 kg/m2, and the following distribution: 2.3% < 20.0 kg/m2, 27.3% from 20.0-24.9 kg/m2, 35.8% from 25.0-29.9 kg/m2, 21.6% from 30.0-34.9 kg/m2, and 13.0% ≥ 35.0 kg/m2. The percent weight change prior to WHISCA enrollment (follow-up weight minus baseline weight, divided by baseline weight and multiplied by 100) averaged 0.1%, with interquartile range -3.1% to 3.4%. The time span defining these changes ranged from 1.1 to 5.6 years, with mean 3.0 years and interquartile range of 2.5 to 3.5 years. Weight gains tended to occur in women who were younger, smokers at WHI baseline, had lower waist/hip ratios, or had no hypertension.
provides the mean and standard deviations of the individual cognitive tests at the initial WHISCA visits, which were used to develop the standardized domain scores. These reflect an average of 5.4 assessments occurring 1.1 to 11.5 years following enrollment in the WHI, with interquartile range 4.0 to 7.0 years.
Women were grouped according to weight gain (≥ 5% gain), weight loss (≥ 5% loss), or remaining stable prior to WHISCA enrollment and their subsequent mean levels of cognitive function (standardized scores) were estimated with full covariate-adjustment (). Women with prior weight loss had mean (standard error) standardized global cognitive function scores of -0.04 (0.02), which were slightly lower than for women who had been weight stable or who had gained weight: 0.02 (0.01) and 0.03 (0.02), respectively, with p=0.04 for differences among groups. Differences among weight change groups were statistically significant (p≤0.05) for verbal knowledge, verbal fluency, and fine motor speed. also included results from pairwise comparisons of mean cognitive function scores among weight change groups. When differences existed, these tended to be between the weight loss and weight stable groups, although for fine motor speed, the differences between the weight loss and weight gain groups also reached statistical significance. For no measure were differences between the weight stable and weight gain groups statistically significant.
Relationships between percent change in weight and standardized measures of average test-specific cognitive function by weight loss (≥5% loss), weight gain (≥5% gain), or stable weight.
portrays results from analyses for different groupings of weight change. Here women are grouped according to the degree of any weight loss (<10% or ≥10%) or weight gain (<10% or ≥10%) and mean global cognitive function scores are computed with full covariate adjustment. As indicated on the figure, women with ≥10% weight loss performed significantly worse than either weight gain group, and those with 10% weight loss performed significantly worse than women gaining <10%. There was not a significant difference between the two weight gain groups.
Association between weight changes and global cognitive function
At WHI enrollment, women had a mean waist circumference of 89.2 cm with interquartile range 79.0 to 98.0 cm, with average percent change 0.0% with interquartile range - 3.6% to 3.4% prior to WHISCA. Changes in weight and waist circumference were modestly correlated r=0.35. Among the factors listed in , only two were significantly associated with changes in waist circumference. Women with waist hip ratios <0.80 averaged 1.37 cm increases while others averaged 0.71 cm decreases (p<0.0001). Mean waist circumference increased among women on placebo (0.47 cm for the CEE-Alone trial and 0.41cm for the CEE+MPA trial) and decreased for women on active therapy (-0.51 cm for CEE-Alone and -0.34 for CEE+MPA) (p = 0.008). Changes in waist circumference were not related to any of the tests of cognitive function, with or without full covariate adjustment (data not shown). The associations between weight changes and cognition were not materially altered by including waist circumference changes as an additional covariate and no interactions between weight and waist circumference changes in joint models of associations with cognition were significant.
Percent weight changes were inversely associated with baseline BMI: mean (SE) changes were 0.11 (0.84) for BMI < 20 kg/m2(N=53), 1.10 (0.25) for BMI 20-24 kg/m2 (N=621), 0.05 (0.21) for BMI 25-29 kg/m2 (N=814), -0.30 (0.27) for BMI 30-34 kg/m2 (N=491), and -1.32 (0.36) for BMI ≥35 kg/m2 (N=295). At WHI enrollment, 10.6% of women reported that they were currently following a low calorie diet. Reporting a low calorie diet was associated with lower cognitive test scores for attention and working memory (p < 0.001) and higher scores on fine motor speed (p = 0.03). When included in the regression models underlying , low calorie diet had no influence on estimates or inference tests and did not have significant interactions with associations involving weight changes.
The reported (FFQ) mean caloric intake of women at WHI enrollment was 1599 kilocalories (interquartile range 1146 to 1929 kilocalories). When quartile of intake (coded 1-4) was included as a covariate in regression models, it was significantly associated with global cognitive function (p=0.002), figural memory (p=0.002), verbal memory (p<0.001), and fine motor speed (p=0.04). In each case, the direction of association was positive: higher reported caloric intake was associated with better cognitive performance. Including this covariate did not materially influence the estimated regression coefficients relating changes in weight to mean cognitive performance. No interactions between weight changes and kilocalorie intake reached statistical significance.