Sleep Disorders and Cognitive Aging Among Cognitively Impaired Versus Unimpaired Older Adults.

BACKGROUND AND OBJECTIVES: Sleep disorders often predict or co-occur with cognitive decline. Yet, little is known about how the relationship unfolds among older adults at risk for cognitive decline. To examine the associations of sleep disorders with cognitive decline in older adults with unimpaired cognition or impaired cognition (mild cognitive impairment and dementia). RESEARCH DESIGN AND METHODS: A total of 5,822 participants (Mage = 70) of the National Alzheimer's Coordinating Center database with unimpaired or impaired cognition were followed for 3 subsequent waves. Four types of clinician-diagnosed sleep disorders were reported: sleep apnea, hyposomnia/insomnia, REM sleep behavior disorder, or "other." Cognition over time was measured by the Montreal Cognitive Assessment (MoCA) or an estimate of general cognitive ability (GCA) derived from scores based on 12 neuropsychological tests. Growth curve models were estimated adjusting for covariates. RESULTS: In participants with impaired cognition, baseline sleep apnea was related to better baseline MoCA performance (b = 0.65, 95% confidence interval [95% CI] = [0.07, 1.23]) and less decline in GCA over time (b = 0.06, 95% CI = [0.001, 0.12]). Baseline insomnia was related to better baseline MoCA (b = 1.54, 95% CI = [0.88, 2.21]) and less decline in MoCA over time (b = 0.56, 95% CI = [0.20, 0.92]). Furthermore, having more sleep disorders (across the 4 types) at baseline predicted better baseline MoCA and GCA, and less decline in MoCA and GCA over time. These results were only found in those with impaired cognition and generally consistent when using self-reported symptoms of sleep apnea or insomnia. DISCUSSION AND IMPLICATIONS: Participants with sleep disorder diagnoses may have better access to healthcare, which may help maintain cognition through improved sleep.

The role of caregiving in cognitive function and change: The REGARDS study.

Chronic stress is associated with negative health outcomes, including poorer cognition. Some studies found stress from caregiving associated with worse cognitive functioning; however, findings are mixed. The present study examined the relationship between caregiving, caregiving strain, and cognitive functioning. We identified participants in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study who were family caregivers at baseline assessment and used propensity matching on 14 sociodemographic and health variables to identify matched noncaregivers for comparison. Data included up to 14 years of repeated assessments of global cognitive functioning, learning and memory, and executive functioning. Our results showed that when compared to noncaregivers, caregivers had better baseline scores on global cognitive functioning and word list learning (WLL). Among caregivers, a lot of strain was associated with better WLL and delayed word recall in the unadjusted model only. Caregivers with a lot of strain had higher depressive symptoms but not significantly higher high-sensitivity c-reactive protein (hsCRP) at baseline compared to caregivers with no or some strain after covariate adjustment. Although caregiving can be highly stressful, we found caregiving status and caregiving strain were not associated with cognitive decline. More methodologically rigorous studies are needed, and conclusions that caregiving has negative effects on cognition should be viewed with caution. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

How Social Connection and Engagement Relate to Functional Limitations and Depressive Symptoms Outcomes After Stroke.

BACKGROUND: Stroke commonly leads to disability and depression. Social connection and engagement can be protective against functional decline and depression in the general population. We investigated the effects of social connection and engagement on trajectories of function and depressive symptoms in stroke. METHODS: This is a longitudinal study, which included 898 participants with incident stroke from the HRS study (Health and Retirement Study) between 1998 and 2012. Multilevel modeling was used to examine associations of social connection and engagement with changes in functional limitations in instrumental activities of daily living (IADLs) and depressive symptoms over time. Models controlled for age, gender, education, and race/ethnicity. Moderation analyses examined whether high social connection and engagement reduced depressive symptoms for survivors with high IADL impairment. RESULTS: Social connection and engagement were generally associated with fewer IADL limitations and depressive symptoms at the time of stroke and after stroke. For example, participants who felt lonely and did not provide help to others before stroke had more IADL limitations. Prestroke volunteering was associated with less increase in IADL limitations with stroke and increase in having friends and providing help to others compared with one's prestroke status were associated with fewer IADL limitations after stroke. For depressive symptoms, participants who felt lonely and did not have a friend or partner before stroke had more depressive symptoms, and participants who had children residing nearby before stroke showed less increase in depressive symptoms. Moderation effects were not found for social connection and engagement on high IADL impairment and depressive symptoms. CONCLUSIONS: Findings suggest that social connection and engagement may reduce the negative physical and psychological outcomes of stroke, both at baseline and after stroke. Efforts to enhance social engagement and diminish loneliness may both enhance population well-being and enhance resilience and recovery from stroke and other illnesses.

"How Social Connection and Engagement Relate to Functional Limitations and Depressive Symptoms Outcomes After Stroke".

Background: Stroke commonly leads to disability and depression. Social connection and engagement can be protective against functional decline and depression in the general population. We investigated the effects of social connection and engagement on trajectories of function and depressive symptoms in stroke. Methods: Participants were 898 individuals with incident stroke from the Health and Retirement Study between 1998-2012. Multilevel modeling was used to examine associations of social connection and engagement with changes in functional limitations in instrumental activities of daily living (IADLs) and depressive symptoms over time. Models controlled for age, gender, education, and race/ethnicity. Moderation analyses examined whether high social connection and engagement reduced depressive symptoms for survivors with high IADL impairment. Results: Social connection and engagement were generally associated with fewer IADL limitations and depressive symptoms at the time of stroke and after stroke. For example, participants who felt lonely and did not provide help to others before stroke had more IADL limitations. Pre-stroke volunteering was associated with less increase in IADL limitations with stroke and increase in having friends and providing help to others compared to one's pre-stroke status were associated with fewer IADL limitations after stroke. For depressive symptoms, participants who felt lonely and did not have a friend or partner before stroke had more depressive symptoms, and participants who had children residing nearby before stroke showed less increase in depressive symptoms. Moderation effects were not found for social connection and engagement on high IADL impairment and depressive symptoms. Conclusions: Findings suggest that social connection and engagement may reduce the negative physical and psychological outcomes of stroke, both at baseline and after stroke. Efforts to enhance social engagement and diminish loneliness may both enhance population well-being and enhance resilience and recovery from stroke and other illnesses.

A risk-based approach for cell line development, manufacturing and characterization of genetically engineered, induced pluripotent stem cell-derived allogeneic cell therapies.

Advances in cellular reprogramming and gene-editing approaches have opened up the potential for a new class of ex vivo cell therapies based on genetically engineered, induced pluripotent stem cell (iPSC)-derived allogeneic cells. While these new therapies share some similarities with their primary cell-derived autologous and allogeneic cell therapy predecessors, key differences exist in the processes used for generating genetically engineered, iPSC-derived allogeneic therapies. Specifically, in iPSC-derived allogeneic therapies, donor selection and gene-editing are performed once over the lifetime of the product as opposed to as part of the manufacturing of each product batch. The introduction of a well-characterized, fully modified, clonally derived master cell bank reduces risks that have been inherent to primary-cell derived autologous and allogeneic therapies. Current regulatory guidance, which was largely developed based on the learnings gained from earlier generation therapies, leaves open questions around considerations for donor eligibility, starting materials and critical components, cell banking and genetic stability. Here, a risk-based approach is proposed to address these considerations, while regulatory guidance continues to evolve.

Goldilocks at work: Just the right amount of job demands may be needed for your sleep health.

OBJECTIVES: It has been reported that job demands affect sleep, but how different levels of job demands affect sleep remains unclear. We examined whether curvilinear relationships exist between job demands and multiple sleep health outcomes. DESIGN: Cross-sectional analyses with linear and quadratic effects, using self-administered survey data. SETTING: A national sample of US adults. PARTICIPANTS: Workers from Midlife in the United States Study (MIDUS2; n = 2927). MEASUREMENTS: The Job Content Questionnaire assessed overall and 5 specific aspects of job demands (intensity, role conflict, work overload, time pressure, and interruptions). Habitual sleep health patterns across 5 dimensions (regularity, satisfaction/quality, daytime alertness, efficiency, and duration) were assessed. Age, sex, race/ethnicity, marital/partnered status, education, job tenure, work hours, body mass index, smoking status, and study sample were covariates. RESULTS: There were significant linear and quadratic relationships between job demands and sleep outcomes. Specifically, the linear effects indicated that participants with higher job demands had worse sleep health, such as shorter duration, greater irregularity, greater inefficiency, and more sleep dissatisfaction. The quadratic effects, however, indicated that sleep regularity and efficiency outcomes were the best when participants' job demands were moderate rather than too low or too high. These effects were found for overall job demands as well as for specific aspects of job demands. Stratified analyses further revealed that these curvilinear associations were mainly driven by participants with low job control. CONCLUSIONS: Moderate levels of job demands, especially if combined with adequate job control, are related to optimal sleep health.

Moderating effect of cognitive reserve on brain integrity and cognitive performance.

Background: Dementia syndrome is one of the most devastating conditions in older adults. As treatments to stop neurodegeneration become available, accurate and timely diagnosis will increase in importance. One issue is that cognitive performance sometimes does not match the corresponding level of neuropathology, affecting diagnostic accuracy. Cognitive reserve (CR), which can preserve cognitive function despite underlying neuropathology, explains at least some variability in cognitive performance. We examined the influence of CR proxies (education and occupational position) on the relationship between hippocampal or total gray matter volume and cognition. Methods: We used data from the Czech Brain Aging Study. Participants were clinically confirmed to be without dementia (n = 457, including subjective cognitive decline and amnestic mild cognitive impairment) or with dementia syndrome (n = 113). Results: For participants without dementia, higher education magnified the associations between (a) hippocampal volume and executive control (b = 0.09, p = 0.033), (b) total gray matter volume and language (b = 0.12, p < 0.001), and (c) total gray matter volume and memory (b = 0.08, p = 0.018). Similarly, higher occupational position magnified the association between total gray matter volume and (a) attention/working memory (b = 0.09, p = 0.009), (b) language (b = 0.13, p = 0.002), and (c) memory (b = 0.10, p = 0.013). For participants with dementia, the associations between hippocampal (b = -0.26, p = 0.024) and total gray matter (b = -0.28, p = 0.024) volume and visuospatial skills decreased in magnitude with higher education. Conclusion: We found that the association between brain volume and cognitive performance varies based on CR, with greater CR related to a stronger link between brain volume and cognition before, and a weaker link after, dementia diagnosis.

The Role of Social Connection/Engagement in Episodic Memory Change in Stroke.

BACKGROUND AND OBJECTIVES: Positive associations between social connection/engagement and cognitive function are well documented. However, little is known about whether social connection/engagement can buffer the impact of serious brain injury such as stroke on cognitive functioning. RESEARCH DESIGN AND METHODS: Participants were 898 individuals with incident stroke from the Health and Retirement Study between 1998 and 2012. Multilevel modeling was used to examine how social connection/engagement was associated with episodic memory pre- and poststroke. Models controlled for age, gender, education, race/ethnicity, number of health conditions, and functional health. RESULTS: Participants who were lonely prestroke recalled significantly fewer words at the time of stroke, and participants who had children residing within 10 miles prestroke showed significantly less decline in word recall over time. Participants who provided help to others prestroke showed less stroke-related decline in word recall. Within-person increase in partnered status, having friends, and helping others were related to better word recall in the poststroke period. DISCUSSION AND IMPLICATIONS: Higher prestroke levels of social connection/engagement predicted better episodic memory at stroke, a smaller decline in episodic memory with stroke, and less decline in episodic memory over time. Increases in social connection/engagement from pre- to poststroke also predicted better poststroke episodic memory. Beyond the widely documented benefits of social connection/engagement to well-being, they may also increase cognitive stimulation and cognitive reserve and thus contribute to stroke recovery in the cognitive domain. Social connection/engagement is an important and modifiable risk factor in older adults.

Change in Episodic Memory With Spousal Loss: The Role of Social Relationships.

OBJECTIVES: The spousal relationship is one of the most important social contexts in old age, and the loss of a spouse/partner is associated with stress and cognitive decline. In the present study, we examined whether social relationships can buffer potential negative effects of spousal loss on cognition. We examined the role of social network, social activities, and perceived deficiencies in social relationships (loneliness). METHOD: We used longitudinal data between 1998 and 2012 from 2,074 participants of the Health and Retirement Study, who had experienced spousal loss during the study period. Multilevel modeling was used to examine how time-varying indicators of social network, social activities, and loneliness were related to age-related trajectories of episodic memory prior to and after spousal loss. Analyses controlled for gender, race/ethnicity, education, time-varying functional health, and being repartnered/remarried. RESULTS: Having children living within 10 miles and providing help to others buffered negative effects of widowhood on episodic memory. In addition, within-person increase in providing help to others buffered against decline in episodic memory after spousal loss. Having friends in the neighborhood, more frequent social visits, providing help to others, volunteering, and lack of loneliness were related to higher episodic memory, while having relatives in the neighborhood was related to lower episodic memory. DISCUSSION: Our findings suggest that social networks, social activities, and loneliness are related to levels of cognitive function at the time of spousal loss and that social relationships can buffer negative effects of spousal loss on cognitive function. Implications for future research are discussed.

The Association Between Homocysteine and Memory in Older Adults.

BACKGROUND: Identifying modifiable risk factors for cognitive decline can reduce burden of dementia. OBJECTIVE: We examined whether homocysteine was associated with memory performance, mediated by entorhinal volume, hippocampal volume, total gray matter volume, or white matter lesions, and moderated by APOE ɛ4 allele, B vitamins, creatinine, total cholesterol, or triglycerides. METHODS: All 204 members of the Czech Brain Aging Study with subjective cognitive decline (SCD; n = 60) or amnestic mild cognitive impairment (aMCI; n = 144) who had valid data were included. Linear regression was used, followed by conditional process modeling to examine mediation and moderation. RESULTS: Controlling for age, sex, and education, higher homocysteine was related to poorer memory performance overall (b = -0.03, SE = 0.01, p = 0.017) and in participants with SCD (b = -0.06, SE = 0.03, p = 0.029), but less so in aMCI (b = -0.03, SE = 0.02, p = 0.074); though sensitivity analyses revealed a significant association when sample was reduced to aMCI patients with more complete cognitive data (who were also better functioning; b = -0.04, SE = 0.02, p = 0.022). Results were unchanged in fully adjusted models. Neither mediation by markers of brain integrity nor moderation by APOE ɛ4, B vitamins, creatinine, and cardiovascular factors were significant. Memory sub-analyses revealed that results for SCD were likely driven by non-verbal memory. The homocysteine-memory relationship was significant when hippocampal volume was below the median (b = -0.04, SE = 0.02, p = 0.046), but not at/above the median (p = 0.247). CONCLUSION: Higher homocysteine levels may adversely influence memory performance, which appears particularly apparent in those without cognitive impairment. Results appear to be independent of brain health, suggesting that homocysteine may represent a good target for intervention.

Job Strain and Trajectories of Cognitive Change Before and After Retirement.

OBJECTIVES: We examined associations between job strain and trajectories of change in cognitive functioning (general cognitive ability plus verbal, spatial, memory, and speed domains) before and after retirement. METHODS: Data on indicators of job strain, retirement age, and cognitive factors were available from 307 members of the Swedish Adoption/Twin Study of Aging. Participants were followed up for up to 27 years (mean = 15.4, SD = 8.5). RESULTS: In growth curve analyses controlling for age, sex, education, depressive symptoms, cardiovascular health, and twinness, greater job strain was associated with general cognitive ability (estimate = -1.33, p = .002), worse memory (estimate = -1.22, p = .007), speed (estimate = -1.11, p = .012), and spatial ability (estimate = -0.96, p = .043) at retirement. Greater job strain was also associated with less improvement in general cognitive ability before retirement and a somewhat slower decline after retirement. The sex-stratified analyses showed that the smaller gains of general cognitive ability before retirement (estimate = -1.09, p = .005) were only observed in women. Domain-specific analyses revealed that greater job strain was associated with less improvement in spatial (estimate = -1.35, p = .010) and verbal (estimate = -0.64, p = .047) ability before retirement in women and a slower decline in memory after retirement in women (estimate = 0.85, p = .008) and men (estimate = 1.12, p = .013). Neither preretirement nor postretirement speed was affected significantly by job strain. DISCUSSION: Greater job strain may have a negative influence on overall cognitive functioning prior to and at retirement, while interrupting exposure to job strain (postretirement) may slow the rate of cognitive aging. Reducing the level of stress at work should be seen as a potential target for intervention to improve cognitive aging outcomes.

Cognitive Reserve, Alzheimer's Neuropathology, and Risk of Dementia: A Systematic Review and Meta-Analysis.

Cognitive reserve (CR) may reduce the risk of dementia. We summarized the effect of CR on progression to mild cognitive impairment (MCI) or dementia in studies accounting for Alzheimer's disease (AD)-related structural pathology and biomarkers. Literature search was conducted in Web of Science, PubMed, Embase, and PsycINFO. Relevant articles were longitudinal, in English, and investigating MCI or dementia incidence. Meta-analysis was conducted on nine articles, four measuring CR as cognitive residual of neuropathology and five as composite psychosocial proxies (e.g., education). High CR was related to a 47% reduced relative risk of MCI or dementia (pooled-hazard ratio: 0.53 [0.35, 0.81]), with residual-based CR reducing risk by 62% and proxy-based CR by 48%. CR protects against MCI and dementia progression above and beyond the effect of AD-related structural pathology and biomarkers. The finding that proxy-based measures of CR rivaled residual-based measures in terms of effect on dementia incidence underscores the importance of early- and mid-life factors in preventing dementia later.

Job Strain and Late-Life Cognition: Findings From the Puerto Rican Elderly Health Conditions Study.

Objectives: We examined associations between job strain and cognitive aging in a sample of older Puerto Ricans. Methods: Members of the Puerto Rican Elderly: Health Conditions study, aged 60-100 years at baseline, participated. Job strain indicators were quantified from O*NET (n = 1632) and a matrix of Job Content Questionnaire scores (JCQ; n = 1467). Global cognition was assessed twice across 4 years. Results: Controlling for age, sex, depressive symptoms, financial problems, hypertension, diabetes, childhood economic hardship, low job control and high job strain were consistently associated with greater cognitive decline. Adding education attenuated these associations. High education strengthened the JCQ job control-cognitive change link. Discussion: Low job control and high job strain may accelerate cognitive aging in this population. However, it may be more difficult to disentangle the intersecting roles of education and job strain in cognitive aging among older Puerto Ricans relative to older adults from contiguous United States or Europe.

Real-time demonstration of a mHealth app designed to reduce college students hazardous drinking.

Heavy alcohol use is a serious health issue in the United States with consequences such as illness, injury, and death. College students are among the most vulnerable to problems associated with risky drinking. This demographic is known as the Net Generation because members have grown up with digital technologies such as smartphones and apps. Thus, mobile health (mHealth) applications, successful in the delivery of health information and interventions to tech-savvy individuals, are a promising means of reaching them. To that end, we developed a smartphone application (SmarTrek) that targets college students and aims to reduce risky alcohol use. SmarTrek features are easy to use and have interactive components including text messages that incorporate motivational interviewing and ecological momentary interventions. We conducted iterative theater testing, field testing, and focus groups to evaluate the acceptability of SmarTrek with college students. We identified salient issues that might arise from SmarTrek use and modified the app based on feedback from participants. Participants were assigned to 2 groups (Group 1 [n = 4] and Group 2 [n = 6]). At baseline, participants completed 2 standardized surveys. Following their field testing, each group of participants was then invited to a focus group session of the app in which they provided feedback. The majority of participants (90%) agreed that SmarTrek was easy to use and that the information provided was useful and had a positive effect on decreasing their drinking. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

NICU Culture of Care for Infants with Neonatal Abstinence Syndrome: A Focused Ethnography.

PURPOSE: The purpose of this focused ethnography was to describe the culture of care and nonpharmacologic nursing interventions performed by NICU nurses for infants with neonatal abstinence syndrome (NAS). METHOD: Roper and Shapira's framework for the analysis included participant observation, individual interviews, and examination of existing documents. SAMPLE: Twelve full-time nurses were observed and interviewed. RESULTS: Results described the culture of care provided to infants with NAS by NICU nurses as evidenced by six themes: learn the baby (routine care, comfort care, environment, adequate rest and sleep, feeding), core team relationships (support, interpersonal relationships), role satisfaction (nurturer/comforter, becoming an expert), grief, making a difference (wonderful insanity, critical to them), and education and care of the mother.

The effects of autonomous difficulty selection on engagement, motivation, and learning in a motion-controlled video game task.

This experiment investigated the relationship between motivation, engagement, and learning in a video game task. Previous studies have shown increased autonomy during practice leads to superior retention of motor skills, but it is not clear why this benefit occurs. Some studies suggest this benefit arises from increased motivation during practice; others suggest the benefit arises from better information processing. Sixty novice participants were randomly assigned to a self-controlled group, who chose the progression of difficulty during practice, or to a yoked group, who experienced the same difficulty progression but did not have choice. At the end of practice, participants completed surveys measuring intrinsic motivation and engagement. One week later, participants returned for a series of retention tests at three different difficulty levels. RM-ANCOVA (controlling for pre-test) showed that the self-controlled group had improved retention compared to the yoked group, on average, ß=46.78, 95% CI=[2.68, 90.87], p=0.04, but this difference was only statistically significant on the moderate difficulty post-test (p=0.004). The self-controlled group also showed greater intrinsic motivation during practice, t(58)=2.61, p=0.01. However, there was no evidence that individual differences in engagement (p=0.20) or motivation (p=0.87) were associated with learning, which was the relationship this experiment was powered to detect. These data are inconsistent with strictly motivational accounts of how autonomy benefits learning, instead suggesting the benefits of autonomy may be mediated through other mechanisms. For instance, within the information processing framework, the learning benefits may emerge from learners appropriately adjusting difficulty to maintain an appropriate level of challenge (i.e., maintaining the relationship between task demands and cognitive resources).

The Relationship Between Engagement and Neurophysiological Measures of Attention in Motion-Controlled Video Games: A Randomized Controlled Trial.

BACKGROUND: Video games and virtual environments continue to be the subject of research in health sciences for their capacity to augment practice through user engagement. Creating game mechanics that increase user engagement may have indirect benefits on learning (ie, engaged learners are likely to practice more) and may also have direct benefits on learning (ie, for a fixed amount of practice, engaged learners show superior retention of information or skills). OBJECTIVE: To manipulate engagement through the aesthetic features of a motion-controlled video game and measure engagement's influence on learning. METHODS: A group of 40 right-handed participants played the game under two different conditions (game condition or sterile condition). The mechanics of the game and the amount of practice were constant. During practice, event-related potentials (ERPs) to task-irrelevant probe tones were recorded during practice as an index of participants' attentional reserve. Participants returned for retention and transfer testing one week later. RESULTS: Although both groups improved in the task, there was no difference in the amount of learning between the game and sterile groups, countering previous research. A new finding was a statistically significant relationship between self-reported engagement and the amplitude of the early-P3a (eP3a) component of the ERP waveform, such that participants who reported higher levels of engagement showed a smaller eP3a (beta=-.08, P=.02). CONCLUSIONS: This finding provides physiological data showing that engagement elicits increased information processing (reducing attentional reserve), which yields new insight into engagement and its underlying neurophysiological properties. Future studies may objectively index engagement by quantifying ERPs (specifically the eP3a) to task-irrelevant probes.

Implementing Electronic Tablet-Based Education of Acute Care Patients.

Poor education-related discharge preparedness for patients with heart failure is believed to be a major cause of avoidable rehospitalizations. Technology-based applications offer innovative educational approaches that may improve educational readiness for patients in both inpatient and outpatient settings; however, a number of challenges exist when implementing electronic devices in the clinical setting. Implementation challenges include processes for "on-boarding" staff, mediating risks of cross-contamination with patients' device use, and selling the value to staff and health system leaders to secure the investment in software, hardware, and system support infrastructure. Strategies to address these challenges are poorly described in the literature. The purpose of this article is to present a staff development program designed to overcome challenges in implementing an electronic, tablet-based education program for patients with heart failure.

Supplements of 20 microg/d cholecalciferol optimized serum 25-hydroxyvitamin D concentrations in 80% of premenopausal women in winter.

The serum 25-hydroxyvitamin D [25(OH)D] response to daily supplementation with 20 microg cholecalciferol (D3) during winter in predominantly white premenopausal women living in Maine was measured and the effects of body composition and hormonal contraceptive use on baseline serum 25(OH)D concentrations and the response to supplementation were examined. A total of 112 women (22.2 +/- 3.7 y old) received placebo from March 2005 until September 2005 when they were randomized to receive either placebo or 20 microg/d D3 through February 2006. Eighty-six women completed the study. Actual mean D3 content of the supplements was 22 microg per capsule. In February 2005 the serum 25(OH)D concentration was 62.0 +/- 23.4 nmol/L (mean +/- SD). Serum 25(OH)D concentrations increased by 35.3 +/- 23.2 nmol/L from February 2005 to February 2006 in the treatment group, significantly more than the 10.9 +/- 16.9 nmol/L increase in the placebo group. Treatment group, magnitude of summer increase in 25(OH)D, estrogen dose, and baseline serum 25(OH)D concentrations, but not body fat, were significant predictors of the 1-y change in 25(OH)D concentrations used to assess the magnitude of the response to supplementation. Daily supplementation with 20 microg D3 during winter achieved optimal 25(OH)D concentrations (> or = 75 nmol/L) in 80% of participants, indicating that this dose is adequate to optimize vitamin D status in most young women in Maine.