GE-ASSOCIATED MEMORY impairment affects an estimated one fifth to one third of older individuals and has important individual, family, and societal costs. 1,2 In older postmenopausal women, the potential impact of declining levels of sex hormones on cognitive functioning has received particular attention because of estrogen's presumptive beneficial effects on neurotransmitters, 3 neuroconnectivity, 4,5 and neuroprotection. 6 Observational studies have suggested that long-term hormone therapy may attenuate cognitive aging in postmenopausal women, although ran-domized clinical trial results are inconsistent. 7-12 The Women's Health Initiative (WHI) includes 2 randomized trials of post-menopausal hormone therapy: the estrogen-alone trial of conjugated equine estrogen (CEE) therapy in women with a prior hysterectomy and the estrogen Author Affiliations and Financial Disclosures are listed at the end of this article.

The effect of CEE + MPA on cognitive function varies across cognitive domains in older women, reflecting both possible beneficial and detrimental actions of ovarian steroids on the aging brain. Our results extend prior findings about dementia and global cognitive function to age-related changes in specific cognitive functions and suggest directions for future research.

Objective Examine the relationship between 1- and 2-month weight loss (WL) and 8-year WL among participants enrolled in a lifestyle intervention. Design & Methods 2290 Look AHEAD participants (BMI: 35.65±5.93kg/m2) with type 2 diabetes received an intensive behavioral WL intervention. Results 1 and 2-month WL were associated with yearly WL through Year 8 (p’s<0.0001). At Month 1, participants losing 2-4% and >4% had 1.62 (95% CI:1.32,1.98) and 2.79 (95% CI:2.21,3.52) times higher odds of achieving a ≥5% WL at Year 4 and 1.28 (95% CI:1.05,1.58) and 1.77 (95% CI:1.40,2.24) times higher odds of achieving a ≥5% at Year 8, compared to those losing <2% initially. At Month 2, a 3-6% WL resulted in greater odds of achieving a ≥5% WL at Year 4 (OR=1.85; CI:1.48,2.32) and a >6% WL resulted in the greatest odds of achieving a ≥5% WL at Year 4 (OR=3.85; CI:3.05,4.88) and Year 8 (OR=2.28; CI:1.81,2.89), compared to those losing <3%. Differences in adherence between WL categories were observed as early as Month 2. Conclusions 1 and 2-month WL was associated with 8-year WL. Future studies should examine whether alternative treatment strategies can be employed to improve treatment outcomes among those with low initial WL.

These results confirm the usefulness of post-menopausal hormone therapy for hot flashes, show convincingly that estrogen plus progestin causes breast discomfort, and demonstrate little influence of postmenopausal hormones on anxiety, cognition, or affect.

Weight losses in lifestyle interventions are variable, yet prediction of long-term success is difficult. Objective We examined the utility of using various weight loss thresholds in the first 2 months of treatment for predicting 1-year outcomes. Design and Methods Participants included 2327 adults with type 2 diabetes (BMI:35.8±6.0) randomized to the intensive lifestyle intervention (ILI) of the Look AHEAD trial. ILI included weekly behavioral sessions designed to increase physical activity and reduce caloric intake. 1-month, 2-month, and 1-year weight changes were calculated. Results Participants failing to achieve a ≥2% weight loss at Month 1 were 5.6 (95% CI:4.5,7.0) times more likely to also not achieve a ≥10% weight loss at Year 1, compared to those losing ≥2% initially. These odds were increased to 11.6 (95% CI:8.6,15.6) when using a 3% weight loss threshold at Month 2. Only 15.2% and 8.2% of individuals failing to achieve the ≥2% and ≥3% thresholds at Months 1 and 2 respectively, go on to achieve a ≥10% weight loss at Year 1. Conclusions Given the association between initial and 1-year weight loss, the first few months of treatment may be an opportune time to identify those who are unsuccessful and utilize rescue efforts.

The subgingival microbiologic composition of diseased periodontal sites was evaluated by darkfield microscopy before and after scaling or local delivery of tetracycline. A standardized sampling and counting method using a crevicular washing technique was developed to determine both numbers and proportions of morphotypes using darkfield microscopy. Tetracycline-loaded hollow fibers established an initial intrasulcular concentration of 200,000 micrograms/ml, which decreased exponentially to 15 micrograms/ml in 24 hours. Repetitive intrasulcular placement of these fibers at periodontitis sites produced an incremental reduction in bacterial counts over a 10-day period. Monolithic fibers made of ethylene vinyl acetate loaded with 25% tetracycline hydrochloride provided sustained release for 10 days under in vitro test conditions. Ten patients were treated in a study comparing the effects of these fibers with scaling. Fibers were placed subgingivally to fill pockets to their probable depth and covered with a periodontal dressing which was maintained for 10 days. The average intrasulcular tetracycline concentration measured at the end of the 10-day period was 643 micrograms/ml. At these sites, total counts, spirochetes, motile rods and nonmotile rods were significantly reduced immediately following treatment. Total counts were depressed to levels near the detection limit of darkfield microscopy. In comparison, scaling produced much smaller alterations of darkfield counts which were not statistically significant.

IMPORTANCE Generalized anxiety disorder (GAD) is common in older adults; however, access to treatment may be limited, particularly in rural areas.OBJECTIVE To examine the effects of telephone-delivered cognitive behavioral therapy (CBT) compared with telephone-delivered nondirective supportive therapy (NST) in rural older adults with GAD. DESIGN, SETTING, AND PARTICIPANTS Randomized clinical trial in the participants' homes of 141 adults aged 60 years and older with a principal or coprincipal diagnosis of GAD who were recruited between January 27, 2011, and October 22, 2013.INTERVENTIONS Telephone-delivered CBT consisted of as many as 11 sessions (9 were required) focused on recognition of anxiety symptoms, relaxation, cognitive restructuring, the use of coping statements, problem solving, worry control, behavioral activation, exposure therapy, and relapse prevention, with optional chapters on sleep and pain. Telephonedelivered NST consisted of 10 sessions focused on providing a supportive atmosphere in which participants could share and discuss their feelings and did not provide any direct suggestions for coping. MAIN OUTCOMES AND MEASURESPrimary outcomes included interviewer-rated anxiety severity (Hamilton Anxiety Rating Scale) and self-reported worry severity (Penn State Worry Questionnaire-Abbreviated) measured at baseline, 2 months' follow-up, and 4 months' follow-up. Mood-specific secondary outcomes included self-reported GAD symptoms (GAD Scale 7 Item) measured at baseline and 4 months' follow-up and depressive symptoms (Beck Depression Inventory) measured at baseline, 2 months' follow-up, and 4 months' follow-up. Among the 141 participants, 70 were randomized to receive CBT and 71 to receive NST.RESULTS At 4 months' follow-up, there was a significantly greater decline in worry severity among participants in the telephone-delivered CBT group (difference in improvement, −4.07; 95% CI, −6.26 to −1.87; P = .004) but no significant differences in general anxiety symptoms (difference in improvement, −1.52; 95% CI, −4.07 to 1.03; P = .24). At 4 months' follow-up, there was a significantly greater decline in GAD symptoms (difference in improvement, −2.36; 95% CI, −4.00 to −0.72; P = .005) and depressive symptoms (difference in improvement, −3.23; 95% CI, −5.97 to −0.50; P = .02) among participants in the telephone-delivered CBT group. CONCLUSIONS AND RELEVANCEIn this trial, telephone-delivered CBT was superior to telephone-delivered NST in reducing worry, GAD symptoms, and depressive symptoms in older adults with GAD.TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01259596.

This review discusses major findings from the Women's Health Initiative Memory Study (WHIMS). WHIMS reported hormone therapy (HT) - conjugated equine estrogen (CEE) with or without medroxyprogesterone acetate (MPA) - increased the risk for dementia (HR 1.76 [95% CI, 1.19-2.60]; P=0.005) and global cognitive decline, with a mean decrement relative to placebo of 0.21 points on the Modified Mini Mental State Examination (3MS) (P=0.006) in women age 65 and older. A subset of WHIMS participants joined the ancillary WHI Study of Cognitive Aging (WHISCA) trials, in which domain-specific cognitive tests and mood were measured annually. Compared with placebo, CEE+MPA had a negative impact on verbal memory over time (p=0.01); and CEE-Alone was associated with lower spatial rotational ability (p=<.01) at the initial assessment, but the difference diminished over time. The ancillary WHIMS-MRI study measured subclinical cerebrovascular disease to possibly explain the negative cognitive findings reported by WHIMS and the increased clinical stroke in older women reported by the WHI. WHIMS-MRI reported that while CEE+MPA and CEE-Alone were not associated with increased ischemic brain lesion volume relative to placebo; both CEE+MPA and CEE-Alone were associated with lower mean brain volumes in the hippocampus (p=0.05); frontal lobe (p=0.004);and total brain (p=0.07). HT-associated reductions in hippocampal volumes were greatest in women with baseline 3MS scores ≤ 90.