Adult Changes In Thought Study Research Articles

Association of remote traumatic brain injury and military employment with late-life trajectories of depressive symptom severity

BackgroundTraumatic brain injury (TBI) and military service are common lifetime exposures among current older adults that may affect late-life mental health. The objective of the present study was to evaluate the association between TBI with loss of consciousness (LOC) and military employment and late-life depressive symptom severity trajectory. Methods1445 males and 2096 females adults at least 65 years old without dementia or recent TBI were enrolled and followed biennially for up to 10 years in the Adult Changes in Thought study from Kaiser Permanente Washington in Seattle, Washington. ResultsUsing group-based trajectory modeling, we documented four distinct depressive symptom severity trajectories that followed a similar course in males and females (Minimal, Decreasing, Increasing, and Persistent). In multinomial regression analyses, TBI with LOC in males was associated with greater likelihood of Persistent versus Minimal depressive symptom severity compared to individuals without TBI (OR = 1.51, 95% CI: 1.01, 2.27; p=0.046). Males reporting past military employment had greater likelihood of Decreasing versus Minimal depressive symptom severity compared to individuals without past military employment (OR = 1.54, 95% CI: 1.03, 2.31; p=0.035). There was no association between TBI or military employment and depression trajectories in females, and no evidence of effect modification by age or between exposures. LimitationsLifetime history of TBI was ascertained retrospectively and may be subject to recall bias. Also, past military employment does not presuppose combat exposure. ConclusionsRemote TBI and past military employment are relevant to late-life trajectories of depressive symptom severity in dementia-free older males.

Fine Particulate Matter and Dementia in the Adult Changes in Thought Study

Background: Air pollution may be associated with elevated dementia risk, but prior research has limitations that may affect reliability, and no prior studies have evaluated this question in a community-based cohort of men and women in the United States. Methods: We evaluated the association of long-term fine particulate matter (PM2.5) exposure with all-cause dementia during the period 1978-2018 in the Adult Changes in Thought (ACT) study based in Seattle, Washington, USA. PM2.5 exposures linked to participant addresses were obtained from a spatiotemporal model spanning 40 years. Research quality dementia diagnoses were made using standardized diagnosis protocols at biennial follow-ups. We conducted multivariate Cox proportional hazards regression to evaluate the association between time-varying, 10-year average PM2.5 exposure and time to event in a model based on age, stratified by apolipoprotein E (APOE) genotype, and adjusted for sex, education, race, neighborhood median household income, and calendar time. Findings: Mean (standard deviation) 10-year average PM2.5 was 10.0 (2.9) µg/m3, which is below the current national air quality standard. Each 1 µg/m3 increase in the moving average of 10-year PM2.5 was associated with a 16% greater hazard of all-cause dementia (1.16 (1.03, 1.31). Interpretation: In this community-based prospective cohort study with uniquely extensive exposure data and research quality outcome ascertainment, elevated long-term exposure to PM2.5 was associated with an increased hazard of all-cause dementia. These results add to growing evidence on the neurodegenerative effects of air pollution and suggest that reducing exposures across the population could contribute to reducing the burden of dementia. Funding: NIEHS F31ES030972-02, NIEHS T32ES015459, NIA T32AG052354, NIEHS and NIA R01ES026187, U01 AG006781, NIEHS ES026187, NIA AG05136, R01 AG056711 and U01 NS091272, the University of Washington Retirement Association Aging Fellowship, and the Seattle Chapter of the Achievement Rewards for College Scientists (ARCS) Foundation. Declaration of Interests: The authors have no conflicts of interest to disclose. Ethics Approval Statement: ACT participants signed forms indicating their informed consent to enroll in the study. Study procedures were approved by the University of Washington and Kaiser Permanente Institutional Review Boards.

Association of Demographic and Early-Life Socioeconomic Factors by Birth Cohort With Dementia Incidence Among US Adults Born Between 1893 and 1949

Early-life factors may be important for later dementia risk. The association between a more advantaged early-life environment, as reflected through an individual's height and socioeconomic status indicators, and decreases in dementia incidence by birth cohort is unknown. To examine the association of birth cohort and early-life environment with dementia incidence among participants in the Adult Changes in Thought study from 1994 to 2015. This prospective cohort study included 4277 participants from the Adult Changes in Thought study, an ongoing longitudinal population-based study of incident dementia in a random sample of adults 65 years and older who were born between 1893 and 1949 and are members of Kaiser Permanente Washington in the Seattle region. Participants in the present analysis were followed up from 1994 to 2015. At enrollment, all participants were dementia-free and completed a baseline evaluation. Subsequent study visits were held every 2 years until a diagnosis of dementia, death, or withdrawal from the study. Participants were categorized by birth period (defined by historically meaningful events) into 5 cohorts: pre-World War I (1893-1913), World War I and Spanish influenza (1914-1920), pre-Great Depression (1921-1928), Great Depression (1929-1939), and World War II and postwar (1940-1949). Participants' height, educational level, childhood financial stability, and childhood household density were examined as indicators of early-life environment, and later-life vascular risk factors for dementia were assessed. Cox proportional hazards regression models, adjusted for competing survival risk, were used to analyze data. Data were analyzed from June 1, 2018, to April 29, 2020. Participants completed the Cognitive Abilities Screening Instrument every 2 years to assess global cognition. Those with scores indicative of cognitive impairment completed an evaluation for dementia, with dementia diagnoses determined during consensus conferences using criteria from the Diagnostic and Statistical Manual of Mental Disorders, 4th edition. Among 4277 participants, the mean (SD) age was 74.5 (6.4) years, and 2519 participants (58.9%) were women. The median follow-up was 8 years (interquartile range, 4-12 years), with 730 participants developing dementia over 24 378 person-years. The age-specific dementia incidence was lower for those born in 1929 and later compared with those born earlier. Compared with participants born in the pre-Great Depression years (1921-1928), the age- and sex-adjusted hazard ratio was 0.67 (95% CI, 0.53-0.85) for those born in the Great Depression period (1929-1939) and 0.62 (95% CI, 0.29-1.31) for those born in the World War II and postwar period (1940-1949). Although indicators of a more advantaged early-life environment and higher educational level (college or higher) were associated with a lower incidence of dementia, these variables did not explain the association between birth cohort and dementia incidence, which remained when vascular risk factors were included and were similar by sex. Age-specific dementia incidence was lower in participants born after the mid-1920s compared with those born earlier. In this population, the decrease in dementia incidence may reflect societal-level changes or individual differences over the life course rather than early-life environment, as reflected through recalled childhood socioeconomic status and measured height, educational level, and later-life vascular risk.

Glucose control and cognitive and physical function in adults 80+ years of age with diabetes.

IntroductionWe modeled associations between glycated hemoglobin (HbA1c) levels (<7%, 7% to 8%, and >8%) and cognitive and physical function among adults 80+ years of age with diabetes and determined whether associations differ by frailty, multimorbidity, and disability.MethodsA total of 316, adults with diabetes, 80+ years of age, were from the Adult Changes in Thought Study. The Cognitive Abilities Screening Instrument Item Response Theory (CASI‐IRT) measured cognition. Short performance‐based physical function (sPPF) and gait speed measured physical function. Glycosylated hemoglobin (HbA1c) levels were from clinical measurements. Analyses estimated associations between average HbA1c levels (<7%, 7% to 8%, and >8%) and functional outcomes using linear regressions estimated with generalized estimating equations.ResultssPPF scores did not differ significantly by HbA1c levels. Gait speed did, but only for non‐frail individuals; those with HbA1c >8% were slower (‐0.10 m/s [95% CI, −0.16 to −0.04]) compared to those with HbA1c 7% to 8%. The association between HbA1c and CASI‐IRT varied with age (interaction P = 0.04). At age 80, for example, relative to people with HbA1c levels of 7% to 8%, CASI‐IRT scores were, on average, 0.18 points lower (95% CI, −0.35 to −0.02) for people with HbA1c <7% and 0.22 points lower (95% CI, −0.40 to −0.05) for people with HbA1c >8%. At older ages, these estimated differences were attenuated. Estimated associations were not modified by multimorbidity or disability.DiscussionModerate HbA1c levels of 7% to 8% were associated with better cognition in early but not late octogenarians with diabetes. Furthermore, HbA1c >8% was associated with slower gait speed among those without frailty. These results add to an evidence base for determining glucose targets for very old adults with diabetes.

Association Between Medications Acting on the Central Nervous System and Fall-Related Injuries in Community-Dwelling Older Adults: A New User Cohort Study.

It is well established that individual medications that affect the central nervous system (CNS) increase falls risk in older adults. However, less is known about risks associated with taking multiple CNS-active medications. Employing a new user design, we used data from the Adult Changes in Thought study, a prospective cohort of community-dwelling people aged 65 and older without dementia. We created a time-varying composite measure of CNS-active medication exposure from electronic pharmacy fill data and categorized into mutually exclusive categories: current (within prior 30 days), recent (31-90 days), past (91-365 days), or nonuse (no exposure in prior year). We calculated standardized daily dose and identified new initiation. Cox proportional hazards models examined the associations between exposures and the outcome of fall-related injury identified from health plan electronic databases. Two thousand five hundred ninety-five people had 624 fall-related injuries over 15,531 person-years of follow-up. Relative to nonuse, fall-related injury risk was significantly greater for current use of CNS-active medication (hazard ratio [HR] = 1.95; 95% CI = 1.57-2.42), but not for recent or past use. Among current users, increased risk was noted with all doses. Risk was increased for new initiation compared with no current use (HR = 2.81; 95% CI = 2.09-3.78). Post hoc analyses revealed that risk was especially elevated with new initiation of opioids. We found that current use, especially new initiation, of CNS-active medications was associated with fall-related injury in community-dwelling older adults. Increased risk was noted with all dose categories. Risk was particularly increased with new initiation of opioids.

ASSOCIATION OF 10-YEAR WALKING TRAJECTORIES WITH COGNITIVE FUNCTION IN OLDER ADULTS: ADULT CHANGES IN THOUGHT STUDY

We identified trajectories of older adults’ walking and their associations with cognitive function. Data on walking (days/week) were collected at baseline of the Adult Changes in Thought study and every two years for 10 years. Cognitive function was assessed by the Cognitive Abilities Screening Instrument (CASI) at year 12. Group-based trajectory analyses identified trajectories among 763 participants (baseline age 70±5 years, 60% female). Regression models, adjusted for baseline sociodemographic and health factors, examined associations with cognitive function. Five walking trajectories were identified: consistently inactive (18.1%), medium active (21.9%), early decline (15.8%), late decline (18.4%), and consistently active (25.8%). Mean CASI score was 92.0 (SD 6.9). CASI scores were lower in early b = -1.66 (95%CI: -2.97, -0.35) and late decline b = -1.89 (-3.26, -0.51) groups, with no difference in consistently active and inactive groups, compared to the medium active trajectory group. Ten-year walking trajectories may determine late-life cognitive function.

Resistance and resilience to Alzheimer\u2019s disease pathology are associated with reduced cortical pTau and absence of limbic-predominant age-related TDP-43 encephalopathy in a community-based cohort

Alzheimer’s disease neuropathologic change (ADNC) is defined by progressive accumulation of β-amyloid plaques and hyperphosphorylated tau (pTau) neurofibrillary tangles across diverse regions of brain. Non-demented individuals who reach advanced age without significant ADNC are considered to be resistant to AD, while those burdened with ADNC are considered to be resilient. Understanding mechanisms underlying ADNC resistance and resilience may provide important clues to treating and/or preventing AD associated dementia. ADNC criteria for resistance and resilience are not well-defined, so we developed stringent pathologic cutoffs for non-demented subjects to eliminate cases of borderline pathology. We identified 14 resistant (85+ years old, non-demented, Braak stage ≤ III, CERAD absent) and 7 resilient (non-demented, Braak stage VI, CERAD frequent) individuals out of 684 autopsies from the Adult Changes in Thought study, a long-standing community-based cohort. We matched each resistant or resilient subject to a subject with dementia and severe ADNC (Braak stage VI, CERAD frequent) by age, sex, year of death, and post-mortem interval. We expanded the neuropathologic evaluation to include quantitative approaches to assess neuropathology and found that resilient participants had lower neocortical pTau burden despite fulfilling criteria for Braak stage VI. Moreover, limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) was robustly associated with clinical dementia and was more prevalent in cases with high pTau burden, supporting the notion that resilience to ADNC may depend, in part, on resistance to pTDP-43 pathology. To probe for interactions between tau and TDP-43, we developed a C. elegans model of combined human (h) Tau and TDP-43 proteotoxicity, which exhibited a severe degenerative phenotype most compatible with a synergistic, rather than simply additive, interaction between hTau and hTDP-43 neurodegeneration. Pathways that underlie this synergy may present novel therapeutic targets for the prevention and treatment of AD.

The Association Between Central Nervous System-Active Medication Use and Fall-Related Injury in Community-Dwelling Older Adults with Dementia.

To examine the association between central nervous system (CNS)-active medication use and the risk of fall-related injury in community-dwelling older adults following dementia onset. Further, to evaluate increased risk at higher doses or with a greater number of CNS-active medication classes. Participants included community-dwelling older adults aged 65years and older with a dementia diagnosis participating in the Adult Changes in Thought Study. From automated pharmacy data, a time-varying composite measure of CNS-active medication use was created. Central nervous system-active medication use was classified as current (use within prior 30days), recent (prior 31-90days), past (prior 91-365days), and nonuse (no exposure in prior year). For current users, standardized daily doses (SDDs) were calculated for each CNS-active medication and summed across medications, and the number of CNS-active medication classes used was also measured. The outcome was fall-related injury based on emergency department, inpatient, and outpatient International Classification of Diseases, Ninth Revision (ICD-9) and external cause of injury (E) codes. Among 793 subjects, 303 fall-related injuries occurred over a mean follow-up of 3.7years (2907 total person-years). Relative to nonuse, fall risk was significantly higher for current use (adjusted hazard ratio [HR] 1.59, 95% confidence internal [CI] 1.19-2.12) but not for past or recent use. Among current users, increased risk was seen across SDD levels: HRs (95% CI): 1.77 (1.19-2.62), 1.79 (1.25-2.56), and 1.35 (0.96-1.92) for less than 1 SDD, 1 to less than 2 SDDs, and 2 or more SDDs, respectively (trend test, p=0.14). A trend was seen for increasing risk with a greater number of CNS-active medication classes; however, this was not statistically significant (trend test, p=0.084). Current use of CNS-active medications was associated with fall-related injury in community-dwelling older adults followed from time of dementia onset, with increased risk even with use of low doses.

Cognitive Resilience to Alzheimer's Disease Pathology in the Human Brain.

Past research has focused on risk factors for developing dementia, with increasing recognition of "resilient" people who live to old age with intact cognitive function despite pathological features of Alzheimer's disease (AD). To evaluate demographic factors, mid-life characteristics, and non-AD neuropathology findings that may be associated with cognitive resilience to AD pathology. We analyzed data from 276 autopsy cases with intermediate or high levels of AD pathology from the Adult Changes in Thought study. We defined cognitive resilience as having Cognitive Abilities Screening Instrument scores ≥86 within two years of death and no clinical dementia diagnosis; non-resilient people had dementia diagnoses from AD or other causes before death. We compared mid-life characteristics, demographics, and additional neuropathology findings between resilient and non-resilient people. We used multivariable logistic regression to estimate odds ratios (ORs) with 95% confidence intervals (CIs) for being resilient compared to not being resilient adjusting for demographic and neuropathology factors. We classified 68 (25%) people as resilient and 208 (75%) as not resilient. A greater proportion of resilient people had a college degree (50%) compared with non-resilient (32%, p = 0.01). The odds of being resilient were significantly increased among people with a college education (OR = 2.01, 95% CI = 1.01-3.99) and significantly reduced among people with additional non-AD neuropathology findings such as hippocampal sclerosis (OR = 0.28, 95% CI = 0.09-0.89) and microinfarcts (OR = 0.34, 95% CI = 0.15-0.78). Increased education and absence of non-AD pathology may be independently associated with cognitive resilience, highlighting the importance of evaluating co-morbid factors in future research on mechanisms of cognitive resilience.

Serum Cholesterol and Incident Alzheimer's Disease: Findings from the Adult Changes in Thought Study.

To evaluate associations between high-density lipoprotein cholesterol (HDL) and non-HDL-C levels at specific ages and subsequent Alzheimer's disease (AD) risk. Prospective population-based cohort study. Adult Changes in Thought (ACT) Study. Individuals aged 65 and older with no dementia at ACT Study entry. We identified separate, partially overlapping subcohorts of ACT participants who were eligible for each age band-specific analysis (50-59, n = 1,088; 60-69, n = 2,852; 70-79, n = 2,344; 80-89, n = 537). Exposure consisted of clinical measures of total cholesterol (TC) and HDL-C from laboratory data during a given age band. Outcomes of incident AD were assessed post-age band using standard research diagnostic criteria. Statistical analyses used adjusted Cox proportional hazards regression models for each exposure and outcome pair within an age band. Cholesterol exposures were modeled using cubic splines. For non-HDL-C, we found a statistically significant association with AD risk in the 60 to 69 (omnibus p = .005) and 70 to 79 (omnibus p = .04) age bands, suggesting a potential U-shaped relationship (greater risk at low and high levels). For example, in people aged 60 to 69, those with an average non-HDL-C level of 120 mg/DL had a 29% greater AD hazard (hazard ratio (HR)=1.29, 95% confidence interval (CI)=1.04-1.61) than those with an average non-HDL-C level of 160 mg/dL, whereas those with an average non-HDL-C level of 210 mg/dL had a 16% greater hazard (HR=1.16, 95% CI=1.01-1.33). We did not find a statistically significant association between HDL-C and AD risk. People with low (120 mg/dL) and high (210 mg/dL) non-HDL-C levels during their 60s and 70s had modestly higher risk of AD than those with intermediate (160 mg/dL) levels. The extreme age bands (50s and 80s) had small sample sizes. J Am Geriatr Soc 66:2344-2352, 2018.

Associations between recent and established ophthalmic conditions and risk of Alzheimer's disease

IntroductionIdentifying ophthalmic diseases associated with increased risk of Alzheimer's disease (AD) may enable better screening and understanding of those at risk of AD. MethodsDiagnoses of glaucoma, age-related macular degeneration (AMD), and diabetic retinopathy (DR) were based on International Classification of Diseases, 9th revision, codes for 3877 participants from the Adult Changes in Thought study. The adjusted hazard ratio for developing probable or possible AD for recent (within 5 years) and established (>5 years) diagnoses were assessed. ResultsOver 31,142 person-years of follow-up, 792 AD cases occurred. The recent and established hazard ratio were 1.46 (P = .01) and 0.87 (P = .19) for glaucoma, 1.20 (P = .12) and 1.50 (P < .001) for AMD, and 1.50 (P = .045) and 1.50 (P = .03) for DR. DiscussionIncreased AD risk was found for recent glaucoma diagnoses, established AMD diagnoses, and both recent and established DR. People with certain ophthalmic conditions may have increased AD risk.

Assessing robustness of hazard ratio estimates to outcome misclassification in longitudinal panel studies with application to Alzheimer's disease.

Analyses of imperfectly assessed time to event outcomes give rise to biased hazard ratio estimates. This bias is a common challenge for studies of Alzheimer’s Disease (AD) because AD neuropathology can only be identified through brain autopsy and is therefore not available for most study participants. Clinical AD diagnosis, although more widely available, has imperfect sensitivity and specificity relative to AD neuropathology. In this study we present a sensitivity analysis approach using a bias-adjusted discrete proportional hazards model to quantify robustness of results to misclassification of a time to event outcome and apply this method to data from a longitudinal panel study of AD. Using data on 1,955 participants from the Adult Changes in Thought study we analyzed the association between average glucose level and AD neuropathology and conducted sensitivity analyses to explore how estimated hazard ratios varied according to AD classification accuracy. Unadjusted hazard ratios were closer to the null than estimates obtained under most scenarios for misclassification investigated. Confidence interval estimates from the unadjusted model were substantially underestimated compared to adjusted estimates. This study demonstrates the importance of exploring outcome misclassification in time to event analyses and provides an approach that can be undertaken without requiring validation data.

Accelerated failure time models for semi-competing risks data in the presence of complex censoring.

Statistical analyses that investigate risk factors for Alzheimer's disease (AD) are often subject to a number of challenges. Some of these challenges arise due to practical considerations regarding data collection such that the observation of AD events is subject to complex censoring including left-truncation and either interval or right-censoring. Additional challenges arise due to the fact that study participants under investigation are often subject to competing forces, most notably death, that may not be independent of AD. Towards resolving the latter, researchers may choose to embed the study of AD within the "semi-competing risks" framework for which the recent statistical literature has seen a number of advances including for the so-called illness-death model. To the best of our knowledge, however, the semi-competing risks literature has not fully considered analyses in contexts with complex censoring, as in studies of AD. This is particularly the case when interest lies with the accelerated failure time (AFT) model, an alternative to the traditional multiplicative Cox model that places emphasis away from the hazard function. In this article, we outline a new Bayesian framework for estimation/inference of an AFT illness-death model for semi-competing risks data subject to complex censoring. An efficient computational algorithm that gives researchers the flexibility to adopt either a fully parametric or a semi-parametric model specification is developed and implemented. The proposed methods are motivated by and illustrated with an analysis of data from the Adult Changes in Thought study, an on-going community-based prospective study of incident AD in western Washington State.

Impact of home visit capacity on genetic association studies of late-onset Alzheimer's disease

IntroductionFindings for genetic correlates of late-onset Alzheimer's disease (LOAD) in studies that rely solely on clinic visits may differ from those with capacity to follow participants unable to attend clinic visits. MethodsWe evaluated previously identified LOAD-risk single nucleotide variants in the prospective Adult Changes in Thought study, comparing hazard ratios (HRs) estimated using the full data set of both in-home and clinic visits (n = 1697) to HRs estimated using only data that were obtained from clinic visits (n = 1308). Models were adjusted for age, sex, principal components to account for ancestry, and additional health indicators. ResultsLOAD associations nominally differed for 4 of 21 variants; CR1 and APOE variants were significant after Bonferroni correction. DiscussionEstimates of genetic associations may differ for studies limited to clinic-only designs. Home visit capacity should be explored as a possible source of heterogeneity and potential bias in genetic studies.

Human Striatal Dopaminergic and Regional Serotonergic Synaptic Degeneration with Lewy Body Disease and Inheritance of APOE ε4

Cognitive impairment in older individuals is a complex trait that in population-based studies most commonly derives from an individually varying mixture of Alzheimer disease, Lewy body disease, and vascular brain injury. We investigated the molecular composition of synaptic particles from three sources: consecutive rapid autopsy brains from the Adult Changes in Thought Study, a population-based cohort; four aged nonhuman primate brains optimally processed for molecular investigation; and targeted replacement transgenic mice homozygous for APOE ε4. Our major goal was to characterize the molecular composition of human synaptic particles in regions of striatum and prefrontal cortex. We performed flow cytometry to measure six markers of synaptic subtypes, as well as amyloid β 42 and paired helical filament tau. Our results showed selective degeneration of dopaminergic terminals throughout the striatum in individuals with Lewy body disease, and serotonergic degeneration in human ventromedial caudate nucleus from individuals with an APOE ε4 allele. Similar results were seen in mouse caudate nucleus homozygous for APOE ε4 via targeted replacement. Together, extension of these clinical, pathologic, and genetic associations from tissue to the synaptic compartment of cerebral cortex and striatum strongly supports our approach for accurately observing the molecular composition of human synapses by flow cytometry.

Alzheimer's disease neuropathologic change, Lewy body disease, and vascular brain injury in clinic- and community-based samples

We examined the relationships between Alzheimer's disease neuropathologic change (ADNC), Lewy body disease (LBD), and vascular brain injury (VBI) in 2 large autopsy samples. Because findings may differ between study populations, data came from U.S. Alzheimer's Disease Centers contributing to the National Alzheimer's Coordinating Center (n = 2742) and from the population-based Adult Changes in Thought study (n = 499). Regardless of study population, over 50% of participants with ADNC had co-occurring LBD or VBI; the majority of whom had a clinical AD dementia diagnosis prior to death. Overlap of pathologies was similar between studies, especially after standardizing to the distribution of age and dementia status in the Adult Changes in Thought population. LBD, but not VBI, was positively associated with ADNC in both studies. Interestingly, cortical LBD was more common in those with intermediate ADNC compared to low or high ADNC, especially in the National Alzheimer's Coordinating Center (p < 0.001). High prevalence of co-occurring neuropathologies among older adults with dementia has implications for accurate diagnosis of dementia etiologies and development of disease-modifying strategies.

Association of Traumatic Brain Injury With Late-Life Neurodegenerative Conditions and Neuropathologic Findings.

The late effects of traumatic brain injury (TBI) are of great interest, but studies characterizing these effects are limited. To determine whether TBI with loss of consciousness (LOC) is associated with an increased risk for clinical and neuropathologic findings of Alzheimer disease (AD), Parkinson disease (PD), and other dementias. This study analyzed data from the Religious Orders Study (ROS), Memory and Aging Project (MAP), and Adult Changes in Thought study (ACT). All ROS and MAP participants and a subset of ACT participants consent to autopsy. Studies performed annual (ROS and MAP) or biennial (ACT) cognitive and clinical testing to identify incident cases of dementia and AD. The 7130 participants included members of a Seattle-area health care delivery system (ACT), priests and nuns living in orders across the United States (ROS), and Chicago-area adults in retirement communities (MAP). Of these, 1589 underwent autopsy. Primary hypothesis was that TBI with LOC would be associated with increased risk for AD and neurofibrillary tangles. Data were accrued from 1994 to April 1, 2014. Self-reported TBI when the participant was free of dementia, categorized as no more than 1 vs more than 1 hour of LOC. Clinical outcomes included incident all-cause dementia, AD, and PD in all studies and incident mild cognitive impairment and progression of parkinsonian signs in ROS and MAP. Neuropathologic outcomes included neurofibrillary tangles, neuritic plaques, microinfarcts, cystic infarcts, Lewy bodies, and hippocampal sclerosis in all studies. Of 7130 participants (2879 [40.4%] men; overall mean [SD] age, 79.9 [6.9] years), 865 reported a history of TBI with LOC. In 45 190 person-years of follow-up, 1537 incident cases of dementia and 117 of PD were identified. No association was found between TBI with LOC and incident dementia (ACT: HR for TBI with LOC ≤1 hour, 1.03; 95% CI, 0.83-1.27; HR for TBI with LOC >1 hour, 1.18; 95% CI, 0.77-1.78; ROS and MAP: HR for TBI with LOC ≤1 hour, 0.87; 95% CI, 0.58-1.29; HR for TBI with LOC >1 hour, 0.84; 95% CI, 0.44-1.57) or AD (findings similar to those for dementia). Associations were found for TBI with LOC and incident PD in ACT (HR for TBI with LOC >1 hour, 3.56; 95% CI, 1.52-8.28) and progression of parkinsonian signs in ROS and MAP (odds ratio [OR] for TBI with LOC ≤1 hour, 1.65; 95% CI, 1.23-2.21; OR for TBI with LOC >1 hour, 2.23; 95% CI, 1.16-4.29). Traumatic brain injury with LOC was associated with Lewy bodies (any Lewy body in ACT: RR for TBI with LOC >1 hour, 2.64; 95% CI, 1.40-4.99; Lewy bodies in substantia nigra and/or locus ceruleus in ACT: RR for TBI with LOC >1 hour, 3.30; 95% CI, 1.71-6.38; Lewy bodies in frontal or temporal cortex in ACT: RR for TBI with LOC >1 hour, 5.73; 95% CI, 2.18-15.0; ROS and MAP: RR for TBI with LOC ≤1 hour, 1.64; 95% CI, 1.00-2.70; pooled RR for TBI with LOC ≤1 hour, 1.59; 95% CI, 1.06-2.39) and microinfarcts (any cortical microinfarct in ROS and MAP: RR for TBI with LOC >1 hour, 2.12; 95% CI, 1.12-4.01; pooled RR for TBI with LOC >1 hour, 1.58; 95% CI, 1.06-2.35). Pooled clinical and neuropathologic data from 3 prospective cohort studies indicate that TBI with LOC is associated with risk for Lewy body accumulation, progression of parkinsonism, and PD, but not dementia, AD, neuritic plaques, or neurofibrillary tangles.

New News From the Adult Changes in Thought Study: A Long-Standing Living Laboratory of Aging Funded for Five More Years

Background/Aims: Delivery system-based research in enumerated populations provides a unique opportunity to study complex chronic diseases as they develop. Studies of disorders that affect people late in life can be particularly valuable. The Adult Changes in Thought (ACT) study was recently awarded five more years of funding. This makes ACT one of the longest continually funded studies and establishes it as a preeminent living laboratory for aging research.

Predicting 2-Year Risk of Developing Pneumonia in Older Adults without Dementia.

To develop three prognostic indices of varying degree of required detail for 2-year pneumonia risk in older adults. Retrospective cohort study. Group Health (GH), an integrated healthcare delivery system. Community-dwelling dementia-free individuals aged 65 and older who had been GH members for at least 2years before start of follow-up and were enrolled in the Adult Changes in Thought study (N=3,375; development cohort, n=2,250; validation cohort, n=1,125. Potential pneumonia risk factors were identified from questionnaire data and interviewer assessments of functional status, medical history, smoking and alcohol use, cognitive function, personal care, and problem solving. Risk factors were also identified based on physical measures such as grip strength and gait speed and administrative database information on comorbid illnesses, laboratory tests, and prescriptions dispensed. Incident community-acquired pneumonia was defined presumptively from administrative data and validated using medical record review. Participants (59% female) contributed 12,998 visits at which risk factors were assessed; 642 pneumonia events were observed during follow-up. Age, sex, chronic obstructive pulmonary disease, congestive heart failure, body mass index, and use of inhaled or oral corticosteroids were critical predictors in all prognostic indices. A risk score based on these seven variables, information on which is commonly available in electronic medical records (EMRs), had equal or better performance (c-index=0.69 in the validation cohort) than scores including more-detailed data such as functional status. Data commonly available in EMRs can stratify older adults into groups with varying subsequent 2-year pneumonia risk.

INCIDENCE OF DEMENTIA SUBTYPES IN A COMMUNITY-BASED PROSPECTIVE COHORT STUDY: THE ADULT CHANGES IN THOUGHT (ACT) STUDY

INCIDENCE OF DEMENTIA SUBTYPES IN A COMMUNITY-BASED PROSPECTIVE COHORT STUDY: THE ADULT CHANGES IN THOUGHT (ACT) STUDY