Psychiatric Disorders Are Common Among Older US Veterans Prior to Traumatic Brain Injury.

OBJECTIVE: To estimate the impact of traumatic brain injury (TBI) on prevalence of posttraumatic stress disorder (PTSD), depression, and alcohol and substance use disorders. SETTING: A random sample of Veteran's Health Administration data. PARTICIPANTS: A total of 14 116 veterans aged ≥55 with incident late-life TBI between October 1, 1999, and September 31, 2021, were matched 1:3 on age and TBI date to 42 678 veterans without TBI. DESIGN: Retrospective cohort study. MAIN MEASURES: PTSD, depression, and alcohol and substance use disorders were identified using diagnostic codes. Participants were censored after the first diagnosis during the year before and the year after the TBI or matched date. Prevalence rates of PTSD, depression, alcohol, and substance use disorders were compared before and after incident TBI or matched date using Poisson regression. RESULTS: Pre-TBI prevalence rates of disorders were higher among those with TBI relative to those without TBI. Pre-TBI PTSD prevalence rates (per 1000 person-years) were 126.3 (95% CI, 120.2-132.4) compared to 21.5 (95% CI, 20.1-22.9) in the non-TBI cohort. In adjusted models, TBI was not associated with an increase in the prevalence of any of the studied disorders. CONCLUSIONS: Prevalence rates of depression, PTSD, and alcohol and substance use disorders were 5 to 10 times higher among older veterans before incident TBI. We did not observe an increase in the prevalence of these disorders after incident TBI. Older veterans with these disorders may be at increased risk for TBI.

Association of Plasma Amyloid-ß and Dementia Among Black and White Older Adults.

Background: Plasma amyloid-ß (Aß) has emerged as an important tool to detect risks of Alzheimer's disease and related dementias, although research in diverse populations is lacking. Objective: We compared plasma Aß42/40 by race with dementia risk over 15 years among Black and White older adults. Methods: In a prospective cohort of 997 dementia-free participants (mean age 74±2.9 years, 55% women, 54% Black), incident dementia was identified based on hospital records, medication, and neurocognitive test over 15 years. Plasma Aß42/40 was measured at Year 2 and categorized into low, medium, and high tertile. We used linear regression to estimate mean Aß42/40 by race and race-stratified Cox proportional hazards models to assess the association between Aß42/40 tertile and dementia risk. Results: Black participants had a lower age-adjusted mean Aß 42/40 compared to White participants, primarily among APOE ɛ4 non-carriers (Black: 0.176, White: 0.185, p = 0.035). Among Black participants, lower Aß 42/40 was associated with increased dementia risk: 33% in low (hazard ratios [HR] = 1.77, 95% confidence interval 1.09-2.88) and 27% in medium tertile (HR = 1.67, 1.01-2.78) compared with 18% in high Aß 42/40 tertile; Increased risks were attenuated among White participants: 21% in low (HR = 1.43, 0.81-2.53) and 23% in medium tertile (HR = 1.27, 0.68-2.36) compared with 15% in high Aß 42/40 tertile. The interaction by race was not statistically significant. Conclusions: Among community-dwelling, non-demented older adults, especially APOE ɛ4 non-carriers, Black individuals had lower plasma Aß 42/40 and demonstrated a higher dementia risk with low Aß42/40 compared with White individuals.

Risk of dementia in older veterans with multiple sclerosis.

BACKGROUND: While it is widely accepted that multiple sclerosis (MS) often causes cognitive dysfunction, it is thought that these cognitive symptoms rarely progress to dementia. However, this has not been thoroughly investigated. The objectives of this cohort study are to determine whether people with MS have an increased risk of dementia compared to the general population and to identify factors, such as geographic latitude, which may modify this association. METHODS: We studied data from a random sample of US veterans aged ≥ 55 years followed at Veterans Affairs Health Care Systems nationwide from 1999 to 2019. We identified all patients diagnosed with MS using ICD codes over a two-year baseline period. We then identified a comparison cohort of patients without MS matched 1:1 on sex, age, race, and first encounter date. We constructed Cox proportional hazards regression models to determine the association between MS and dementia while controlling for demographic factors and comorbidities, with additional models to examine subgroup effects. We used Fine-Gray subdistribution hazard models accounting for competing risk of death to evaluate the sensitivity of the findings. RESULTS: The study included 4084 MS patients and a matched group of 4084 non-MS patients. Overall, patients had mean age 66, were 93.6% male, and 88.1% non-Hispanic White, with mean follow-up time 9.5 years (MS) and 10.8 years (non-MS). In unadjusted models, veterans with MS had greater risk of dementia compared to matched controls (cumulative incidence 16.7% vs 12.4%; Cox HR 1.58, 95% CI 1.41-1.78). The increased risk remained after adjustment for potential confounders (adjusted HR 1.56, 95% CI 1.39-1.76) and when considering death as a competing risk (Fine-Gray HR 1.36, 95% CI 1.21-1.53). The magnitude of the MS-dementia association increased with rising geographic latitude (North HR 1.86, 1.51-2.30; Central HR 1.61, 1.42-1.82; South HR 1.39, 1.18-1.64; interaction p = 0.04) and younger baseline age (interaction p<0.001). CONCLUSIONS: Among older veterans with MS, risk of dementia diagnosis was higher compared to matched controls even after controlling for comorbidities. The risk difference was highest in northern regions and in younger patients. Clinicians caring for older MS patients should be aware of this risk and offer screening and treatment accordingly.

Intimate Partner Violence, Mental Health, and Aging-Related Health Among Men and Women Veterans Across the Lifespan.

BACKGROUND: A growing body of evidence suggests adverse health outcomes related to intimate partner violence (IPV), including traumatic brain injury (TBI). However, most research in this area has focused on reproductive-aged women. OBJECTIVE: To examine relationships between IPV (with and without TBI), mental health, and aging-related health outcomes among men and women Veterans across the lifespan. DESIGN: Cross-sectional analysis of Department of Veterans Affairs (VA) administrative data from fiscal years 2000-2019. Descriptive statistics and chi-square analyses were used to compare key comorbidities in matched samples of Veterans with and without IPV (gender-stratified and matched 1:3 based on demographics and index date). Comparisons between those with IPV and TBI relative to IPV alone were also examined. SUBJECTS: Veterans aged 18 + with and without documented IPV in Department of Veterans Affairs (VA) electronic health records (n = 4108 men, 2824 women). MAIN MEASURES: ICD codes were used to identify IPV, TBI, and aging-related medical (sleep disorder, hypertension, diabetes, dementia) and common psychiatric (depression, posttraumatic stress disorder, alcohol use disorder, and substance use disorder) diagnoses. KEY RESULTS: Demographic characteristics were reflective of VA-enrolled Veterans (men: mean age 66, SD 16; 72% non-Hispanic White; women: mean age 47, SD 13; 64% non-Hispanic White). Relative to Veterans without IPV, both men and women with IPV had higher rates of all examined medical (e.g., sleep disorders, men: 33% vs. 52%; women: 45% vs. 63%) and psychiatric diagnoses (e.g., depression, men 32% vs. 74%; women 59% vs. 91%; all ps < .001), with evidence of an additive effect of TBI on some psychiatric outcomes. CONCLUSIONS: IPV is broadly associated with aging-related and mental health, and TBI is a common correlate that may further contribute to psychiatric outcomes. Findings highlight the importance of trauma-informed care and recognizing the potential role of these exposures on men and women Veterans' health across the lifespan.

Dementia Risk and Disadvantaged Neighborhoods.

Importance: Residence in a disadvantaged neighborhood may be associated with an increased risk for cognitive impairment and dementia but is understudied in nationally representative populations. Objective: To investigate the association between the Area Deprivation Index (ADI) and dementia. Design, Setting, and Participants: Retrospective cohort study within the US Veterans Health Administration from October 1, 1999, to September 30, 2021, with a national cohort of older veterans receiving care in the largest integrated health care system in the United States. For each fiscal year, a 5% random sample was selected from all patients (n = 2 398 659). Patients with missing ADI information (n = 492 721) or missing sex information (n = 6) and prevalent dementia cases (n = 25 379) were excluded. Participants had to have at least 1 follow-up visit (n = 1 662 863). The final analytic sample was 1 637 484. Exposure: Neighborhoods were characterized with the ADI, which combines several sociodemographic indicators (eg, income, education, employment, and housing) into a census block group-level index of disadvantage. Participants were categorized into ADI rank quintiles by their census block group of residence (higher ADI rank quintile corresponds with more deprivation). Main Outcome and Measures: Time to dementia diagnosis (using International Classification of Diseases, Ninth Revision and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes) was estimated with Cox proportional hazards models with age as the time scale, and the sensitivity of the findings was evaluated with Fine-Gray proportional hazards models, accounting for competing risk of death. Results: Among the 1 637 484 Veterans Health Administration patients, the mean (SD) age was 68.6 (7.7) years, and 1 604 677 (98.0%) were men. A total of 7318 patients were Asian (0.4%), 151 818 (9.3%) were Black, 10 591 were Hispanic (0.6%), 1 422 713 (86.9%) were White, and 45 044 (2.8%) were of other or unknown race and ethnicity. During a mean (SD) follow-up of 11.0 (4.8) years, 12.8% of veterans developed dementia. Compared with veterans in the least disadvantaged neighborhood quintile, those in greater disadvantage groups had an increased risk of dementia in models adjusted for sex, race and ethnicity, and psychiatric and medical comorbid conditions (first quintile = reference; second quintile adjusted hazard ratio [HR], 1.09 [95% CI, 1.07-1.10]; third quintile adjusted HR, 1.14 [95% CI, 1.12-1.15]; fourth quintile adjusted HR, 1.16 [95% CI, 1.14-1.18]; and fifth quintile adjusted HR, 1.22 [95% CI, 1.21-1.24]). Repeating the main analysis using competing risk for mortality led to similar results. Conclusions and Relevance: Results of this study suggest that residence within more disadvantaged neighborhoods was associated with higher risk of dementia among older veterans integrated in a national health care system.

Traumatic Brain Injury and Long-Term Risk of Stroke Among US Military Veterans.

BACKGROUND: Traumatic brain injury (TBI) is associated with significant morbidity, but the association of TBI with long-term stroke risk in diverse populations remains less clear. Our objective was to examine the long-term associations of TBI with stroke and to investigate potential differences by age, sex, race and ethnicity, and time since TBI diagnosis. METHODS: Retrospective cohort study of US military veterans aged 18+ years receiving healthcare in the Veterans Health Administration system between October 1, 2002 and September 30, 2019. Veterans with TBI were matched 1:1 to veterans without TBI on age, sex, race and ethnicity, and index date, yielding 306 796 veterans with TBI and 306 796 veterans without TBI included in the study. In primary analyses, Fine-Gray proportional hazards models adjusted for sociodemographics and medical/psychiatric comorbidities were used to estimate the association between TBI and stroke risk, accounting for the competing risk of mortality. RESULTS: Participants were a mean age of 50 years, 9% were female, and 25% were of non-White race and ethnicity. Overall, 4.7% of veterans developed a stroke over a median follow-up of 5.2 years. Veterans with TBI had 1.69 times (95% CI, 1.64-1.73) increased risk of any stroke (ischemic or hemorrhagic) compared to veterans without TBI. This increased risk was highest in the first-year post-TBI diagnosis (hazard ratio [HR], 2.16 [95% CI, 2.03-2.29]) but remained elevated for 10+ years. Similar patterns were observed for secondary outcomes, with associations of TBI with hemorrhagic stroke (HR, 3.92 [95% CI, 3.59-4.29]) being stronger than with ischemic stroke (HR, 1.56 [95% CI, 1.52-1.61]). Veterans with both mild (HR, 1.47 [95% CI, 1.43-1.52]) and moderate/severe/penetrating injury (HR, 2.02 [95% CI, 1.96-2.09]) had increased risk of stroke compared to veterans without TBI. Associations of TBI with stroke were stronger among older compared to younger individuals (P interaction-by-age<0.001) and were weaker among Black veterans compared to other race and ethnicities (P interaction-by-race<0.001). CONCLUSIONS: Veterans with prior TBI are at increased long-term risk for stroke, suggesting they may be an important population to target for primary stroke prevention measures.

Cognitive and Functional Trajectories in Older Adults With Prediagnostic Parkinson Disease.

BACKGROUND AND OBJECTIVES: There is increasing interest in characterizing the earliest phases of Parkinson disease (PD). However, few studies have investigated prediagnostic trajectories of cognition and function. Our objective was to describe prediagnostic cognitive and functional trajectories in PD in older women and men. METHODS: We studied 9,595 women and 5,795 men from 2 prospective cohort studies of community-dwelling elders followed up to 20 years. In individuals without prevalent PD, we estimated the associations of incident PD diagnosis with rates of change in cognition and function before and after diagnosis compared with healthy older adults using multivariate mixed-effects models. RESULTS: Over follow-up, 297 individuals developed incident PD. Interactions between the terms in our model and sex were statistically significant for the 3 outcomes (p < 0.001 for all), so we stratified results by sex. Compared with older men without PD, men who developed PD exhibited faster decline in global cognition (0.04 SD more annual change, p < 0.001), executive function (0.05 SD more annual change, p < 0.001), and functional status (0.06 SD more annual change, p < 0.001) in the prediagnostic period. Women who developed PD compared with women without PD displayed faster decline in executive function (0.02 SD more annual change, p = 0.006) and functional status in the prediagnostic period (0.07 SD more annual change, p < 0.001). DISCUSSION: Individuals with incident PD exhibit cognitive and functional decline during the prediagnostic phase that exceeds rates associated with normal aging. Better understanding heterogeneity in prodromal PD is essential to enable earlier diagnosis and identify impactful nonmotor symptoms in all subgroups.

Systematic Review, Meta-Analysis, and Population Attributable Risk of Dementia Associated with Traumatic Brain Injury in Civilians and Veterans.

Traumatic brain injury (TBI) is an established risk factor for dementia. However, the magnitude of risk is highly variable across studies. Identification of sub-populations at highest risk, with careful consideration of potential sources of bias, is urgently needed to guide public health policy and research into mechanisms and treatments. We conducted a systematic review and meta-analysis of risk of all-cause dementia after all-severity TBI. We assessed for effect of participant age and sex, veteran status, research methods, and region. The search window covered January 1990 to January 2019. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines. Thirty-two studies met inclusion criteria. Data were pooled using random effects models. Population attributable risk (PAR) of dementia due to TBI in the U.S. was calculated by sex and veteran status. Pooled risk ratio (RR) for dementia after TBI was 1.66 (95% confidence interval 1.42-1.93). Younger age, male sex, and studies from Asia were associated with significantly higher risk; veteran status was not. Risk of dementia associated with "head injury/trauma" was not significantly different from that associated with "TBI" diagnosis specifically. PAR of dementia due to TBI among U.S. veterans was twice that of the general U.S. population, largely due to the high prevalence of TBI exposure in the majority male veteran population. This meta-analysis found that TBI is associated with nearly 70% increased risk of dementia. Risk may be highest among younger adults, men, and cohorts in Asia. Efforts to prevent TBI and also to prevent post-TBI dementia are of high importance. Additionally, improved methods for diagnosing and tracking TBI on a public health level, such as national registries, may improve the quality and generalizability of future epidemiological studies investigating the association between TBI and dementia.

Comparison Groups Matter in Traumatic Brain Injury Research: An Example with Dementia.

The association between traumatic brain injury (TBI) and risk for Alzheimer disease and related dementias (ADRD) has been investigated in multiple studies, yet reported effect sizes have varied widely. Large differences in comorbid and demographic characteristics between individuals with and without TBI could result in spurious associations between TBI and poor outcomes, even when control for confounding is attempted. Yet, inadvertent control for post-TBI exposures (e.g., psychological and physical trauma) could result in an underestimate of the effect of TBI. Choice of the unexposed or comparison group is critical to estimating total associated risk. The objective of this study was to highlight how selection of the comparison group impacts estimates of the effect of TBI on risk for ADRD. Using data on Veterans aged ≥55 years obtained from the Veterans Health Administration (VA) for years 1999-2019, we compared risk of ADRD between Veterans with incident TBI (n = 9440) and (1) the general population of Veterans who receive care at the VA (All VA) (n = 119,003); (2) Veterans who received care at a VA emergency department (VA ED) (n = 111,342); and (3) Veterans who received care at a VA ED for non-TBI trauma (VA ED NTT) (n = 65,710). In inverse probability of treatment weighted models, TBI was associated with increased risk of ADRD compared with All VA (hazard ratio [HR] 1.94; 95% confidence interval [CI] 1.84, 2.04), VA ED (HR 1.42; 95% CI 1.35, 1.50), and VA ED NTT (HR 1.12; 95% CI 1.06, 1.18). The estimated effect of TBI on incident ADRD was strongly impacted by choice of the comparison group.

Association of Race and Ethnicity With Incidence of Dementia Among Older Adults.

Importance: The racial and ethnic diversity of the US, including among patients receiving their care at the Veterans Health Administration (VHA), is increasing. Dementia is a significant public health challenge and may have greater incidence among older adults from underrepresented racial and ethnic minority groups. Objective: To determine dementia incidence across 5 racial and ethnic groups and by US geographical region within a large, diverse, national cohort of older veterans who received care in the largest integrated health care system in the US. Design, Setting, and Participants: Retrospective cohort study within the VHA of a random sample (5% sample selected for each fiscal year) of 1 869 090 participants aged 55 years or older evaluated from October 1, 1999, to September 30, 2019 (the date of final follow-up). Exposures: Self-reported racial and ethnic data were obtained from the National Patient Care Database. US region was determined using Centers for Disease Control and Prevention (CDC) regions from residential zip codes. Main Outcomes and Measures: Incident diagnosis of dementia (9th and 10th editions of the International Classification of Diseases). Fine-Gray proportional hazards models were used to examine time to diagnosis, with age as the time scale and accounting for competing risk of death. Results: Among the 1 869 090 study participants (mean age, 69.4 [SD, 7.9] years; 42 870 women [2%]; 6865 American Indian or Alaska Native [0.4%], 9391 Asian [0.5%], 176 795 Black [9.5%], 20 663 Hispanic [1.0%], and 1 655 376 White [88.6%]), 13% received a diagnosis of dementia over a mean follow-up of 10.1 years. Age-adjusted incidence of dementia per 1000 person-years was 14.2 (95% CI, 13.3-15.1) for American Indian or Alaska Native participants, 12.4 (95% CI, 11.7-13.1) for Asian participants, 19.4 (95% CI, 19.2-19.6) for Black participants, 20.7 (95% CI, 20.1-21.3) for Hispanic participants, and 11.5 (95% CI, 11.4-11.6) for White participants. Compared with White participants, the fully adjusted hazard ratios were 1.05 (95% CI, 0.98-1.13) for American Indian or Alaska Native participants, 1.20 (95% CI, 1.13-1.28) for Asian participants, 1.54 (95% CI, 1.51-1.57) for Black participants, and 1.92 (95% CI, 1.82-2.02) for Hispanic participants. Across most US regions, age-adjusted dementia incidence rates were highest for Black and Hispanic participants, with rates similar among American Indian or Alaska Native, Asian, and White participants. Conclusions and Relevance: Among older adults who received care at VHA medical centers, there were significant differences in dementia incidence based on race and ethnicity. Further research is needed to understand the mechanisms responsible for these differences.

Sex Differences in the Risk of Dementia in Older Veterans.

BACKGROUND: Studies have demonstrated women to have a higher prevalence of dementia compared to men. However, sex differences in dementia incidence are controversial with conflicting reports showing women with higher, lower, or similar incidence. Source of difference may be due to clinical setting and lack of consideration of competing risk of death. We examined dementia incidence in a sample of the national Veteran population to determine differences by sex. METHODS: We examined data from the Veterans Health Administration (VHA), the largest integrated health care system in the United States. We studied 947 797 Veterans aged ≥55 years (mean age: 69.9 ± 8.4, 3% female) evaluated in the VHA from October 1, 1999 to September 30, 2019. We estimated age-adjusted incidence rates of dementia (International Classification of Diseases, 9th and 10th Edition codes) by sex, and used Fine-Gray proportional hazards models with age as time scale to examine time to diagnosis, accounting for competing risk of death. RESULTS: During the follow-up (mean 8.4 years), 11.3% (n = 106 977, 11.4% men and 8.0% women) of Veterans developed dementia. Age-adjusted incidence was 12.6/1 000 person-years for men and 12.7/1 000 person-years for women. Compared to male Veterans, risk dementia was slightly higher among females (hazard ratio = 1.15; 95% confidence interval: 1.10-1.20), and on average, female Veterans developed dementia 0.2 years earlier than male Veterans. After additional adjustment for race, education, medical, and psychiatric conditions, results were similar. CONCLUSIONS: Among older Veterans in a national cohort, women had a slightly increased risk for developing dementia compared to men after accounting for competing risk of death.

Remote Assessment of Cardiovascular Risk Factors and Cognition in Middle-Aged and Older Adults: Proof-of-Concept Study.

BACKGROUND: Adults with cardiovascular disease risk factors (CVRFs) are also at increased risk of developing cognitive decline and dementia. However, it is often difficult to study the relationships between CVRFs and cognitive function because cognitive assessment typically requires time-consuming in-person neuropsychological evaluations that may not be feasible for real-world situations. OBJECTIVE: We conducted a proof-of-concept study to determine if the association between CVRFs and cognitive function could be detected using web-based, self-administered cognitive tasks and CVRF assessment. METHODS: We recruited 239 participants aged ≥50 years (mean age 62.7 years, SD 8.8; 42.7% [n=102] female, 88.7% [n=212] White) who were enrolled in the Health eHeart Study, a web-based platform focused on cardiac disease. The participants self-reported CVRFs (hypertension, high cholesterol, diabetes, and atrial fibrillation) using web-based health surveys between August 2016 and July 2018. After an average of 3 years of follow-up, we remotely evaluated episodic memory, working memory, and executive function via the web-based Posit Science platform, BrainHQ. Raw data were normalized and averaged into 3 domain scores. We used linear regression models to examine the association between CVRFs and cognitive function. RESULTS: CVRF prevalence was 62.8% (n=150) for high cholesterol, 45.2% (n=108) for hypertension, 10.9% (n=26) for atrial fibrillation, and 7.5% (n=18) for diabetes. In multivariable models, atrial fibrillation was associated with worse working memory (ß=-.51, 95% CI -0.91 to -0.11) and worse episodic memory (ß=-.31, 95% CI -0.59 to -0.04); hypertension was associated with worse episodic memory (ß=-.27, 95% CI -0.44 to -0.11). Diabetes and high cholesterol were not associated with cognitive performance. CONCLUSIONS: Self-administered web-based tools can be used to detect both CVRFs and cognitive health. We observed that atrial fibrillation and hypertension were associated with worse cognitive function even in those in their 60s and 70s. The potential of mobile assessments to detect risk factors for cognitive aging merits further investigation.

Traumatic brain injury, cardiovascular disease, and risk of dementia among older US Veterans.

OBJECTIVE: Traumatic brain injury (TBI) is associated with elevated rates of cardiovascular disease (CVD), and both CVD and TBI are risk factors for dementia. We investigated whether CVD and its risk factors underlie the association between TBI and dementia. MATERIALS AND METHODS: Cox proportional hazards models among 195,416 Veterans Health Administration patients age 55+ with TBI and a non-TBI, age/sex/race-matched comparison sample. RESULTS: Veterans +TBI were more likely to have any CVD diagnosis (24% vs 36% p = <0.001) or risk factor (83 vs. 90% p < .001) compared to -TBI. During follow-up (mean ~7 years), 12.0% of Veterans with TBI only (HR: 2.17 95% CI 2.09-2.25), and 10.3% with CVD only developed dementia (HR 1.21 95% CI 1.15-1.28), compared to 6.5% with neither. There was an additive association between TBI and CVD on dementia risk (HR 2.51, 95% CI 2.41-2.61). Among those +TBI (±CVD), risk was minimally attenuated by adjustment for CVD/CVD risk factors (unadjusted HR: 2.38, 95% CI: 2.31-2.45; adjusted HR: 2.17, 95% CI 2.10-2.23). CONCLUSIONS: Older veterans TBI have increased prevalence of CVD/CVD risk factors. TBI and CVD had an additive statistical association, with dementia risk increased by ~2.5-fold. However, CVD accounted for little of the association between TBI and dementia. More research is needed to understand mechanisms of TBI-dementia and inform clinical guidelines post-TBI.

Early to Midlife Smoking Trajectories and Cognitive Function in Middle-Aged US Adults: the CARDIA Study.

BACKGROUND: Smoking starts in early adulthood and persists throughout the life course, but the association between these trajectories and midlife cognition remains unclear. OBJECTIVE: Determine the association between early to midlife smoking trajectories and midlife cognition. DESIGN: Prospective cohort study. PARTICIPANTS: Participants were 3364 adults (mean age = 50.1 ± 3.6, 56% female, 46% Black) from the Coronary Artery Risk Development in Young Adults (CARDIA) study: 1638 ever smokers and 1726 never smokers. MAIN MEASURES: Smoking trajectories were identified in latent class analysis among 1638 ever smokers using smoking measures every 2-5 years from baseline (age 18-30 in 1985-1986) through year 25 (2010-2011). Poor cognition was based on cognitive domain scores ≥ 1 SD below the mean on tests of processing speed (Digit Symbol Substitution Test), executive function (Stroop), and memory (Rey Auditory Verbal Learning Test) at year 25. RESULTS: Five smoking trajectories emerged over 25 years: quitters (19%), and minimal stable (40%), moderate stable (20%), heavy stable (15%), and heavy declining smokers (5%). Heavy stable smokers showed poor cognition on all 3 domains compared to never smoking (processing speed AOR = 2.22 95% CI 1.53-3.22; executive function AOR = 1.58 95% CI 1.05-2.36; memory AOR = 1.48 95% CI 1.05-2.10). Compared to never smoking, both heavy declining (AOR = 1.95 95% CI 1.06-3.68) and moderate stable smokers (AOR = 1.56 95% CI 1.11-2.19) exhibited slower processing speed, and heavy declining smokers additionally had poor executive function. For minimal stable smokers (processing speed AOR = 1.12 95% CI 0.85-1.51; executive function AOR = 0.97 95% CI 0.71-1.31; memory AOR = 1.21 95% CI 0.94-1.55) and quitters (processing speed AOR = 0.96 95% CI 0.63-1.48; executive function AOR = 0.98 95% CI 0.63-1.52; memory AOR = 0.97 95% CI 0.67-1.39), no association was observed. CONCLUSIONS: The association between early to midlife smoking trajectories and midlife cognition was dose-dependent. Results underscore the cognitive health risk of moderate and heavy smoking and the potential benefits of quitting on cognition, even in midlife.

Atrial Fibrillation is Associated With Greater Risk of Dementia in Older Veterans.

OBJECTIVES: To examine the association of atrial fibrillation (AF) with incident dementia in older veterans and the effect of anticoagulation on that association. METHODS: Around 407,871 veterans aged ≥55 years receiving care from US Veterans Health Administration between August 2003 and September 2015 were included in our retrospective study. AF and incident dementia were determined according to ICD-9-CM codes. Logistic regressions with veterans grouped into high-dimensional propensity scores deciles were used, and a mediation analysis was employed to examine the extent of cardio/cerebrovascular diseases that may also account for that association. RESULTS: AF was associated with greater dementia risk (odds ratio = 1.14; 95% confidence interval 1.07-1.22), partially mediated by cardio/cerebrovascular disease. Among veterans with AF taking anticoagulants, the risk of dementia was 44% higher (odds ratio =1.44; 95% CI 1.27-1.63) compared to those without anticoagulants, likely related to AF severity. CONCLUSION: Our findings underscore the importance of considering cognitive function in the management of AF patients.

Increased risk of dementia in older female US veterans with alcohol use disorder.

AIM: To determine whether alcohol use disorder (AUD) is associated with increased dementia risk among older women veterans. DESIGN: Cohort study. SETTING: United States. PARTICIPANTS: Women veterans with AUD aged ≥ 55 years (n = 2207), receiving care from Veterans Health Administration medical centers from October 2004 to September 2015 with one or more follow-up visit and an age-matched sample of women veterans without AUD (n = 2207). Women at baseline with prevalent dementia or AUD in remission were excluded. MEASUREMENTS: AUD, substance use disorder (SUD), smoking, psychiatric (depression, anxiety, post-traumatic stress disorder, anxiety) and medical comorbidities (diabetes, hypertension, stroke, chronic obstructive pulmonary disorder, traumatic brain disorder) and dementia determined by the International Classification of Diseases, 9th revision, Clinical Modification codes. Cox proportional hazards models were used to determine the association between AUD and dementia risk during follow-up. Sensitivity analyses were performed by excluding women (n = 349) with comorbid SUD and by excluding women (n = 1568) currently smoking. FINDINGS: Veteran women had a mean [standard deviation (SD)] age of 65.0 (5.6) years at baseline. During follow-up (median 4 years, interquartile range: 2-6) 3.7% of women (n = 82) with AUD developed dementia compared with 1.1% (n = 24) without AUD (P < 0.001). After adjustment for demographics, medical and psychiatric conditions and accounting for different Veteran's Integrated Service Networks, the adjusted hazard ratio (aHR) for dementia was 3.12 (95% CI = 1.90-5.12) for women with AUD compared with women without AUD. After removing women with SUD (aHR = 3.53, 95% CI = 2.13-5.85) and women currently smoking (aHR = 3.80, 95% CI = 2.11-6.84), results were similar. CONCLUSIONS: Alcohol use disorder among female US veterans aged more than 55 years appears to be associated with a more than threefold increase of dementia.

Relationships of inflammation trajectories with white matter volume and integrity in midlife.

OBJECTIVE: Elevated inflammation is associated with worse late-life cognitive functioning and brain health. Our goal was to examine the relationship between inflammation trajectories and white matter integrity in midlife. METHODS: Participants were 508 adults from the Coronary Artery Risk Development in Young Adults Study (CARDIA; 51% female). Latent class analysis was used to identify inflammation trajectories based on repeated measures of the inflammatory marker C-reactive protein (CRP) over the 18 years before brain magnetic resonance imaging (MRI). Outcomes were brain MRI measures of total and region-specific white matter volume and integrity at a mean age of 50.6 ± 3.4 years. Linear regression was used to examine if inflammation trajectories were associated with brain MRI outcomes, adjusting for potential confounds in all models and for disease and health behaviors in follow-up models. RESULTS: Lower-stable (38%), moderate-increasing (7%), and consistently-higher (54%), trajectories emerged. Compared to the lower-stable group, the moderate-increasing group showed lower white matter volume (ß = -0.18, 95% CI -0.29, -0.06) and worse white matter integrity as indexed by lower fractional anisotropy (FA; ß = -0.37, 95% CI -0.70, -0.04) and higher mean diffusivity (ß = 0.44, 95% CI 0.11, 0.78) in the whole brain. The consistently-higher group showed lower whole-brain FA (ß = -0.20, -0.38, -0.03). In exploratory analyses, the moderate-increasing group showed lower white matter volume, lower FA and higher MD in the frontal, temporal, and parietal lobes compared to the lower-stable group. The consistently-higher group showed lower white matter volume in the parietal lobe and lower FA in the frontal, temporal, and parietal lobes, but similar MD, compared to the lower-stable group. Findings for the moderate-increasing, but not the consistently-higher, group were robust to adjustment for disease and lifestyle factors. CONCLUSION: Increasing or high inflammation trajectories from early to mid adulthood are associated with worse brain health, as indexed by lower white matter volume and/or worse white matter integrity.

Apathy and risk of probable incident dementia among community-dwelling older adults.

OBJECTIVE: To evaluate the association between baseline apathy and probable incident dementia in a population-based sample of community-dwelling older adults. METHODS: We studied 2,018 white and black community-dwelling older adults from the Health, Aging, and Body Composition (Health ABC) study. We measured apathy at year 6 (our study baseline) with the modified Apathy Evaluation Scale and divided participants into tertiles based on low, moderate, or severe apathy symptoms. Incident dementia was ascertained over 9 years by dementia medication use, hospital records, or clinically relevant cognitive decline on global cognition. We examined the association between apathy and probable incident dementia using a Cox proportional hazards model adjusting for demographics, cardiovascular risk factors, APOE4 status, and depressed mood. We also evaluated the association between the apathy group and cognitive change (as measured by the modified Mini-Mental State Examination and Digit Symbol Substitution Test over 5 years) using linear mixed effects models. RESULTS: Over 9 years of follow-up, 381 participants developed probable dementia. Severe apathy was associated with an increased risk of dementia compared to low apathy (25% vs 14%) in unadjusted (hazard ratio [HR] 1.9, 95% confidence interval [CI] 1.5-2.5) and adjusted models (HR 1.7, 95% CI 1.3-2.2). Greater apathy was associated with worse cognitive score at baseline, but not rate of change over time. CONCLUSION: In a diverse cohort of community-dwelling adults, apathy was associated with increased risk of developing probable dementia. This study provides novel evidence for apathy as a prodrome of dementia.

Cardiovascular risk factors and accelerated cognitive decline in midlife: The CARDIA Study.

OBJECTIVE: Increasing evidence supports an association between midlife cardiovascular risk factors (CVRFs) and risk of dementia, but less is known about whether CVRFs influence cognition in midlife. We examined the relationship between CVRFs and midlife cognitive decline. METHODS: In 2,675 black and white middle-aged adults (mean age 50.2 ± 3.6 years, 57% female, 45% black), we measured CVRFs at baseline: hypertension (31%), diabetes mellitus (11%), obesity (43%), high cholesterol (9%), and current cigarette smoking (15%). We administered cognitive tests of memory, executive function, and processing speed at baseline and 5 years later. Using logistic regression, we estimated the association of CVRFs with accelerated cognitive decline (race-specific decline ≥1.5 SD from the mean change) on a composite cognitive score. RESULTS: Five percent (n = 143) of participants had accelerated cognitive decline over 5 years. Smoking, hypertension, and diabetes mellitus were associated with an increased likelihood of accelerated decline after multivariable adjustment (adjusted odds ratio [AOR] 1.65, 95% confidence interval [CI] 1.00-2.71; AOR 1.87, 95% CI 1.26-2.75; AOR 2.45, 95% CI 1.54-3.88, respectively), while obesity and high cholesterol were not associated with risk of decline. These results were similar when stratified by race. The likelihood of accelerated decline also increased with greater number of CVRFs (1-2 CVRFs: AOR 1.77, 95% CI 1.02-3.05; ≥3 CVRFs: AOR 2.94, 95% CI 1.64-5.28) and with Framingham Coronary Heart Disease Risk Score ≥10 (AOR 2.29, 95% CI 1.21-4.34). CONCLUSIONS: Midlife CVRFs, especially hypertension, diabetes mellitus, and smoking, are common and associated with accelerated cognitive decline at midlife. These results identify potential modifiable targets to prevent midlife cognitive decline and highlight the need for a life course approach to cognitive function and aging.

Condomless Sex and Psychiatric Comorbidity in the Context of Constrained Survival Choices: A Longitudinal Study Among Homeless and Unstably Housed Women.

We sought to identify the prevalence and independent correlates of condomless sex within a cohort of community-recruited homeless and unstably housed cisgender adult women who were followed biannually for 3 years (N = 143 HIV+ , N = 139 HIV-). Nearly half (44%) of participants reported condomless sex in the 6 months before baseline, which increased to 65% throughout the study period. After adjusting for having a primary partner, longitudinal odds of condomless sex among women with HIV were significantly higher among those reporting < daily use of alcohol or cannabis (AOR = 2.09, p =.002, and 1.88, p =.005, respectively) and PTSD (AOR = 1.66, p =.034). Among women without HIV, adjusted longitudinal odds of condomless sex were significantly higher for those reporting < daily methamphetamine use (AOR = 2.02, p =.012), panic attack (AOR = 1.74, p =.029), and homelessness (AOR = 1.67, p = .006). Associations were slightly attenuated when adjusting for sex exchange. Targeted HIV/STI programs for unstably housed women should address anxiety and trauma disorders, infrequent substance use, and housing challenges.