Long-term cognitive outcome after elective hip or knee total joint arthroplasty: A population-based observational study.

BACKGROUND: One year after elective hip or knee total joint arthroplasty (TJA), >30% of older adults meet criteria for postoperative neurocognitive disorder. However, this is not contextualized with long-term cognitive outcomes in comparable surgical and nonsurgical controls. We analyzed population-based data to compare long-term cognitive outcomes in older adults after TJA, other surgeries, and with and without arthritis pain. METHODS: This was a retrospective observational analysis of United States older adults in the Health and Retirement Study (HRS) who underwent elective TJA, or elective surgery without expected functional benefits (e.g., cholecystectomy; inguinal herniorrhaphy), between 1998 and 2018 at aged 65 or older. TJA recipients were also age- and sex-matched to nonsurgical controls who reported moderate-severe arthritic pain or denied pain, so that comparison groups included surgical and nonsurgical (pain-suffering and pain-free) controls. We modeled biennially-assessed memory performance, a measure of direct and proxy cognitive assessments, before and after surgery, normalized to the rate of memory decline ("cognitive aging") in controls to express effect size estimates as excess, or fewer, months of memory decline. We used linear mixed effects models adjusted for preoperative health and demographic factors, including frailty, flexibly capturing time before/after surgery (knots at -4, 0, 8 years; discontinuity at surgery). RESULTS: There were 1947 TJA recipients (average age 74; 63% women; 1358 knee, 589 hip) and 1631 surgical controls (average age 76; 38% women). Memory decline 3 years after TJA was similar to surgical controls (5.2 [95% confidence interval, CI -1.2 to 11.5] months less memory decline in the TJA group, p = 0.11) and nonsurgical controls. At 5 years, TJA recipients experienced 5.0 [95% CI -0.9 to 10.9] months less memory decline than arthritic pain nonsurgical controls. CONCLUSION: There is no systematic accelerated memory decline at 3 years after TJA compared with surgical or nonsurgical controls.

Association of cancer history with structural brain aging markers of Alzheimer's disease and related dementias risk.

INTRODUCTION: Cancer survivors are less likely than comparably aged individuals without a cancer history to develop Alzheimer's disease and related dementias (ADRD). METHODS: In the UK Biobank, we investigated associations between cancer history and five structural magnetic resonance imaging (MRI) markers for ADRD risk, using linear mixed-effects models to assess differences in mean values and quantile regression to examine whether associations varied across the distribution of MRI markers. RESULTS: Cancer history was associated with smaller mean hippocampal volume (b = -19 mm3 , 95% CI = -36, -1) and lower mean cortical thickness in the Alzheimer's disease signature region (b = -0.004 mm, 95% CI = -0.007, -0.000). Quantile regressions indicated individuals most vulnerable to ADRD were more affected by cancer history. DISCUSSION: Some brain MRI markers associated with ADRD risk were elevated in adults with a history of cancer. The magnitude of the adverse associations varied across quantiles of neuroimaging markers, and the pattern suggests possible harmful associations for individuals already at high ADRD risk. HIGHLIGHTS: We found no evidence of an inverse association between cancer history and ADRD-related neurodegeneration. Cancer history was associated with smaller mean hippocampal volume and lower mean cortical thickness in the Alzheimer's disease signature region. Quantile regressions indicated individuals most vulnerable to ADRD were more affected by cancer history.

Association between cancer and dementia risk in the UK Biobank: evidence of diagnostic bias.

Epidemiological studies have identified an inverse association between cancer and dementia. Underlying methodological biases have been postulated, yet no studies have systematically investigated the potential for each source of bias within a single dataset. We used the UK Biobank to compare estimates for the cancer-dementia association using different analytical specifications designed to sequentially address multiple sources of bias, including competing risk of death, selective survival, confounding bias, and diagnostic bias. We included 140,959 UK Biobank participants aged ≥ 55 without dementia before enrollment and with linked primary care data. We used cancer registry data to identify cancer cases prevalent before UK Biobank enrollment and incident cancer diagnosed after enrollment. We used Cox models to evaluate associations of prevalent and incident cancer with all-cause dementia, Alzheimer's disease (AD), and vascular dementia. We used time-varying models to evaluate diagnostic bias. Over a median follow-up of 12.3 years, 3,310 dementia cases were diagnosed. All-site incident cancer was positively associated with all-cause dementia incidence (hazard ratio [HR] = 1.14, 95% CI: 1.02-1.29), but prevalent cancer was not (HR = 1.04, 95% CI: 0.92-1.17). Results were similar for vascular dementia. AD was not associated with prevalent or incident cancer. Dementia diagnosis was substantially elevated in the first year after cancer diagnosis (HR = 1.83, 95% CI: 1.42-2.36), after which the association attenuated to null, suggesting diagnostic bias. Following a cancer diagnosis, health care utilization or cognitive consequences of diagnosis or treatment may increase chance of receiving a dementia diagnosis, creating potential diagnostic bias in electronic health records-based studies.

Association of Behavioral and Clinical Risk Factors With Cataract: A Two-Sample Mendelian Randomization Study.

Purpose: To investigate the association of genetically determined primary open-angle glaucoma (POAG), myopic refractive error (RE), type 2 diabetes (T2D), blood pressure (BP), body mass index (BMI), cigarette smoking, and alcohol consumption with the risk of age-related cataract. Methods: To assess potential causal effects of clinical or behavioral factors on cataract risk, we conducted two-sample Mendelian randomization analyses. Genetic instruments, based on common genetic variants associated with risk factors at genome-wide significance (P < 5 × 10-8), were derived from published genome-wide association studies (GWAS). For age-related cataract, we used GWAS summary statistics from our previous GWAS conducted in the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort (28,092 cataract cases and 50,487 controls; all non-Hispanic whites) or in the UK Biobank (31,852 cataract cases and 428,084 controls; all European-descent individuals). We used the inverse-variance weighted (IVW) method as our primary source of Mendelian randomization estimates and conducted common sensitivity analyses. Results: We found that genetically determined POAG and mean spherical equivalent RE were significantly associated with cataract risk (IVW model: odds ratio [OR] = 1.04; 95% confidence interval [CI], 1.01-1.08; P = 0.018; per diopter more hyperopic: OR = 0.92; 95% CI, 0.89-0.93; P = 6.51 × 10-13, respectively). In contrast, genetically determined T2D, BP, BMI, cigarette smoking, or alcohol consumption were not associated with cataract risk (P > 0.05). Conclusions: Our results provide evidence that genetic risks for POAG and myopia may be causal risk factors for age-related cataract. These results are consistent with previous observational studies reporting associations of myopia with cataract risk. This information may support population cataract risk stratification and screening strategies.

Comparison of Mammography AI Algorithms with a Clinical Risk Model for 5-year Breast Cancer Risk Prediction: An Observational Study.

Background Although several clinical breast cancer risk models are used to guide screening and prevention, they have only moderate discrimination. Purpose To compare selected existing mammography artificial intelligence (AI) algorithms and the Breast Cancer Surveillance Consortium (BCSC) risk model for prediction of 5-year risk. Materials and Methods This retrospective case-cohort study included data in women with a negative screening mammographic examination (no visible evidence of cancer) in 2016, who were followed until 2021 at Kaiser Permanente Northern California. Women with prior breast cancer or a highly penetrant gene mutation were excluded. Of the 324 009 eligible women, a random subcohort was selected, regardless of cancer status, to which all additional patients with breast cancer were added. The index screening mammographic examination was used as input for five AI algorithms to generate continuous scores that were compared with the BCSC clinical risk score. Risk estimates for incident breast cancer 0 to 5 years after the initial mammographic examination were calculated using a time-dependent area under the receiver operating characteristic curve (AUC). Results The subcohort included 13 628 patients, of whom 193 had incident cancer. Incident cancers in eligible patients (additional 4391 of 324 009) were also included. For incident cancers at 0 to 5 years, the time-dependent AUC for BCSC was 0.61 (95% CI: 0.60, 0.62). AI algorithms had higher time-dependent AUCs than did BCSC, ranging from 0.63 to 0.67 (Bonferroni-adjusted P < .0016). Time-dependent AUCs for combined BCSC and AI models were slightly higher than AI alone (AI with BCSC time-dependent AUC range, 0.66-0.68; Bonferroni-adjusted P < .0016). Conclusion When using a negative screening examination, AI algorithms performed better than the BCSC risk model for predicting breast cancer risk at 0 to 5 years. Combined AI and BCSC models further improved prediction. © RSNA, 2023 Supplemental material is available for this article.

Education, incident cancer, and rate of memory decline in a national sample of US adults in mid-to-later-life.

INTRODUCTION: Middle-aged and older adults who develop cancer experience memory loss following diagnosis, but memory decline in the years before and after cancer diagnosis is slower compared to their cancer-free counterparts. Educational attainment strongly predicts memory function during aging, but it is unclear whether education protects against memory loss related to cancer incidence or modifies long-term memory trajectories in middle-aged and older cancer survivors. MATERIALS AND METHODS: Data were from 14,449 adults (3,248 with incident cancer, excluding non-melanoma skin cancer) aged 50+ in the population-based US Health and Retirement Study from 1998 to 2016. Memory was assessed every two years as a composite of immediate and delayed word recall tests and proxy assessments for impaired individuals. Memory scores all time points were standardized at to the baseline distribution. Using multivariate-adjusted linear mixed-effects models, we estimated rates of memory decline in the years before cancer diagnosis, shortly after diagnosis, and in the years after diagnosis. We compared rates of memory decline between incident cancer cases and age-matched cancer-free adults, overall and according to level of education (<12 years, "low"; 12 to <16 years, "intermediate"; ≥16 years, "high"). RESULTS: Incident cancer diagnoses were followed by short-term declines in memory averaging 0.06 standard deviation (SD) units (95% confidence interval [CI]: -0.084, -0.036). Those with low education experienced the strongest magnitude of short-term decline in memory after diagnosis (-0.10 SD units, 95% CI: -0.15, -0.05), but this estimate was not statistically significantly different from the short-term decline in memory experienced by those with high education (-0.04 SD units, 95% CI: -0.08, 0.01; p-value for education as an effect modifier = 0.15). In the years prior to and following an incident cancer diagnosis, higher educational attainment was associated with better memory, but it did not modify the difference in rate of long-term memory decline between cancer survivors and those who remained cancer-free. DISCUSSION: Education was associated with better memory function over time among both cancer survivors and cancer-free adults aged 50 and over. Low education may be associated with a stronger short-term decline in memory after a cancer diagnosis.

The Role of Dementia Diagnostic Delay in the Inverse Cancer-Dementia Association.

BACKGROUND: Cancer is inversely associated with dementia. Using simulations, we examined whether this inverse association may be explained by dementia diagnosis timing, including death before dementia diagnosis and differential diagnosis patterns by cancer history. METHODS: We used multistate Markov simulation models to generate cohorts 65 years of age and free of cancer and dementia at baseline; follow-up for incident cancer (all cancers, breast, prostate, and lung cancer), dementia, dementia diagnosis among those with dementia, and death occurred monthly over 30 years. Models specified no true effect of cancer on dementia, and used age-specific transition rates calibrated to U.S. population and cohort data. We varied the average lapse between dementia onset and diagnosis, including nondifferential and differential delays by cancer history, and examined observed incidence rate ratios (IRRs) for the effect of cancer on dementia diagnosis. RESULTS: Nondifferential dementia diagnosis delay introduced minimal bias (IRRs = 0.98-1.02) for all cancer, breast, and prostate models and substantial bias (IRR = 0.78) in lung cancer models. For the differential dementia diagnosis delay model of all cancer types combined, simulation scenarios with ≥20% lower dementia diagnosis rate (additional 4.5-month delay) in those with cancer history versus without yielded results consistent with literature estimates. Longer dementia diagnosis delays in those with cancer and higher mortality in those with cancer and dementia yielded more bias. CONCLUSIONS: Delays in dementia diagnosis may play a role in the inverse cancer-dementia relationship, especially for more fatal cancers, but moderate differential delays in those with cancer were needed to fully explain the literature-reported IRRs.

Advancing the Social Epidemiology Mission of the American Journal of Epidemiology.

Social epidemiology is concerned with how social forces influence population health. Rather than focusing on a single disease (as in cancer or cardiovascular epidemiology) or a single type of exposure (e.g., nutritional epidemiology), social epidemiology encompasses all the social and economic determinants of health, both historical and contemporary. These include features of social and physical environments, the network of relationships in a society, and the institutions, politics, policies, norms and cultures that shape all of these forces. This commentary presents the perspective of several editors at the Journal with expertise in social epidemiology. We articulate our thinking to encourage submissions to the Journal that: 1) expand knowledge of emerging and underresearched social determinants of population health; 2) advance new empirical evidence on the determinants of health inequities and solutions to advance health equity; 3) generate evidence to inform the translation of research on social determinants of health into public health impact; 4) contribute to innovation in methods to improve the rigor and relevance of social epidemiology; and 5) encourage critical self-reflection on the direction, challenges, successes, and failures of the field.

Explaining the Variance in Cardiovascular Disease Risk Factors: A Comparison of Demographic, Socioeconomic, and Genetic Predictors.

BACKGROUND: Efforts to explain the burden of cardiovascular disease (CVD) often focus on genetic factors or social determinants of health. There is little evidence on the comparative predictive value of each, which could guide clinical and public health investments in measuring genetic versus social information. We compared the variance in CVD-related outcomes explained by genetic versus socioeconomic predictors. METHODS: Data were drawn from the Health and Retirement Study (N = 8,720). We examined self-reported diabetes, heart disease, depression, smoking, and body mass index, and objectively measured total and high-density lipoprotein cholesterol. For each outcome, we compared the variance explained by demographic characteristics, socioeconomic position (SEP), and genetic characteristics including a polygenic score for each outcome and principal components (PCs) for genetic ancestry. We used R-squared values derived from race-stratified multivariable linear regressions to evaluate the variance explained. RESULTS: The variance explained by models including all predictors ranged from 3.7% to 14.3%. Demographic characteristics explained more than half this variance for most outcomes. SEP explained comparable or greater variance relative to the combination of the polygenic score and PCs for most conditions among both white and Black participants. The combination of SEP, polygenic score, and PCs performed substantially better, suggesting that each set of characteristics may independently contribute to the prediction of CVD-related outcomes. Philip R. Lee Institute for Health Policy Studies, Department of Family & Community Medicine, UCSF. CONCLUSIONS: Focusing on genetic inputs into personalized medicine predictive models, without considering measures of social context that have clear predictive value, needlessly ignores relevant information that is more feasible and affordable to collect on patients in clinical settings. See video abstract at, http://links.lww.com/EDE/B879.

The Revolution Will Be Hard to Evaluate: How Co-Occurring Policy Changes Affect Research on the Health Effects of Social Policies.

Extensive empirical health research leverages variation in the timing and location of policy changes as quasi-experiments. Multiple social policies may be adopted simultaneously in the same locations, creating co-occurrence that must be addressed analytically for valid inferences. The pervasiveness and consequences of co-occurring policies have received limited attention. We analyzed a systematic sample of 13 social policy databases covering diverse domains including poverty, paid family leave, and tobacco use. We quantified policy co-occurrence in each database as the fraction of variation in each policy measure across different jurisdictions and times that could be explained by covariation with other policies. We used simulations to estimate the ratio of the variance of effect estimates under the observed policy co-occurrence to variance if policies were independent. Policy co-occurrence ranged from very high for state-level cannabis policies to low for country-level sexual minority-rights policies. For 65% of policies, greater than 90% of the place-time variation was explained by other policies. Policy co-occurrence increased the variance of effect estimates by a median of 57-fold. Co-occurring policies are common and pose a major methodological challenge to rigorously evaluating health effects of individual social policies. When uncontrolled, co-occurring policies confound one another, and when controlled, resulting positivity violations may substantially inflate the variance of estimated effects. Tools to enhance validity and precision for evaluating co-occurring policies are needed.

Association of Coronary Artery Bypass Grafting vs Percutaneous Coronary Intervention With Memory Decline in Older Adults Undergoing Coronary Revascularization.

Importance: It is uncertain whether coronary artery bypass grafting (CABG) is associated with cognitive decline in older adults compared with a nonsurgical method of coronary revascularization (percutaneous coronary intervention [PCI]). Objective: To compare the change in the rate of memory decline after CABG vs PCI. Design, Setting, and Participants: Retrospective cohort study of community-dwelling participants in the Health and Retirement Study, who underwent CABG or PCI between 1998 and 2015 at age 65 years or older. Data were modeled for up to 5 years preceding and 10 years following revascularization or until death, drop out, or the 2016-2017 interview wave. The date of final follow-up was November 2017. Exposures: CABG (including on and off pump) or PCI, ascertained from Medicare fee-for-service billing records. Main Outcomes and Measures: The primary outcome was a summary measure of cognitive test scores and proxy cognition reports that were performed biennially in the Health and Retirement Study, referred to as memory score, normalized as a z score (ie, mean of 0, SD of 1 in a reference population of adults aged ≥72 years). Memory score was analyzed using multivariable linear mixed-effects models, with a prespecified subgroup analysis of on-pump and off-pump CABG. The minimum clinically important difference was a change of 1 SD of the population-level rate of memory decline (0.048 memory units/y). Results: Of 1680 participants (mean age at procedure, 75 years; 41% female), 665 underwent CABG (168 off pump) and 1015 underwent PCI. In the PCI group, the mean rate of memory decline was 0.064 memory units/y (95% CI, 0.052 to 0.078) before the procedure and 0.060 memory units/y (95% CI, 0.048 to 0.071) after the procedure (within-group change, 0.004 memory units/y [95% CI, -0.010 to 0.018]). In the CABG group, the mean rate of memory decline was 0.049 memory units/y (95% CI, 0.033 to 0.065) before the procedure and 0.059 memory units/y (95% CI, 0.047 to 0.072) after the procedure (within-group change, -0.011 memory units/y [95% CI, -0.029 to 0.008]). The between-group difference-in-differences estimate for memory decline for PCI vs CABG was 0.015 memory units/y (95% CI, -0.008 to 0.038; P = .21). There was statistically significant increase in the rate of memory decline after off-pump CABG compared with after PCI (difference-in-differences: mean increase in the rate of decline of 0.046 memory units/y [95% CI, 0.008 to 0.084] after off-pump CABG), but not after on-pump CABG compared with PCI (difference-in-differences: mean slowing of decline of 0.003 memory units/y [95% CI, -0.024 to 0.031] after on-pump CABG). Conclusions and Relevance: Among older adults undergoing coronary revascularization with CABG or PCI, the type of revascularization procedure was not significantly associated with differences in the change of rate of memory decline.

The Association Between Cancer and Spousal Rate of Memory Decline: A Negative Control Study to Evaluate (Unmeasured) Social Confounding of the Cancer-memory Relationship.

Cancer diagnoses are associated with better long-term memory in older adults, possibly reflecting a range of social confounders that increase cancer risk but improve memory. We used spouse's memory as a negative control outcome to evaluate this possible confounding, since spouses share social characteristics and environments, and individuals' cancers are unlikely to cause better memory among their spouses. We estimated the association of an individual's incident cancer diagnosis (exposure) with their own (primary outcome) and their spouse's (negative control outcome) memory decline in 3601 couples from 1998 to 2014 in the Health and Retirement Study, using linear mixed-effects models. Incident cancer predicted better long-term memory for the diagnosed individual. We observed no association between an individual's cancer diagnosis and rate of spousal memory decline. This negative control study suggests that the inverse association between incident cancer and rate of memory decline is unlikely to be attributable to social/behavioral factors shared between spouses.

Association Between Alzheimer Disease and Cancer With Evaluation of Study Biases: A Systematic Review and Meta-analysis.

Importance: Observational studies consistently report inverse associations between cancer and Alzheimer disease (AD). Shared inverse etiological mechanisms might explain this phenomenon, but a systematic evaluation of methodological biases in existing studies is needed. Objectives: To systematically review and meta-analyze evidence on the association between cancer and subsequent AD, systematically identify potential methodological biases in studies, and estimate the influence of these biases on the estimated pooled association between cancer and AD. Data Sources: All-language publications were identified from PubMed, Embase, and PsycINFO databases through September 2, 2020. Study Selection: Longitudinal cohort studies and case-control studies on the risk of AD in older adults with a history of any cancer type, prostate cancer, breast cancer, colorectal cancer, or nonmelanoma skin cancer, relative to those with no cancer history. Data Extraction and Synthesis: Two reviewers independently abstracted the data and evaluated study biases related to confounding, diagnostic bias, competing risks, or survival bias. Random-effects meta-analysis was used to provide pooled estimates of the association between cancer and AD. Metaregressions were used to evaluate whether the observed pooled estimate could be attributable to each bias. The study was designed and conducted according to the Preferring Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Main Outcomes and Measures: Incidence, hazard, or odds ratios for AD comparing older adults with vs without a previous cancer diagnosis. Results: In total, 19 cohort studies and 3 case-control studies of the associations between any cancer type (n = 13), prostate cancer (n = 5), breast cancer (n = 1), and nonmelanoma skin cancer (n = 3) with AD were identified, representing 9 630 435 individuals. In all studies combined, cancer was associated with decreased AD incidence (cohort studies: random-effects hazard ratio, 0.89; 95% CI, 0.79-1.00; case-control studies: random-effects odds ratio, 0.75; 95% CI, 0.61-0.93). Studies with insufficient or inappropriate confounder control or greater likelihood of AD diagnostic bias had mean hazard ratios closer to the null value, indicating that these biases could not explain the observed inverse association. Competing risks bias was rare. Studies with greater likelihood of survival bias had mean hazard ratios farther from the null value. Conclusions and Relevance: The weak inverse association between cancer and AD may reflect shared inverse etiological mechanisms or survival bias but is not likely attributable to diagnostic bias, competing risks bias, or insufficient or inappropriate control for potential confounding factors.

The competing risk of death and selective survival cannot fully explain the inverse cancer-dementia association.

INTRODUCTION: We evaluated whether competing risk of death or selective survival could explain the reported inverse association between cancer history and dementia incidence (incidence rate ratio [IRR] ≈ 0.62-0.85). METHODS: A multistate simulation model of a cancer- and dementia-free cohort of 65-year-olds was parameterized with real-world data (cancer and dementia incidence, mortality), assuming no effect of cancer on dementia (true IRR = 1.00). To introduce competing risk of death, cancer history increased mortality. To introduce selective survival, we included a factor (prevalence ranging from 10% to 50%) that reduced cancer mortality and dementia incidence (IRRs ranged from 0.30 to 0.90). We calculated IRRs for cancer history on dementia incidence in the simulated cohorts. RESULTS: Competing risk of death yielded unbiased cancer-dementia IRRs. With selective survival, bias was small (IRRs = 0.89 to 0.99), even under extreme scenarios. DISCUSSION: The bias induced by selective survival in simulations was too small to explain the observed inverse cancer-dementia link, suggesting other mechanisms drive this association.

Predictive Value of Breast MRI Background Parenchymal Enhancement for Neoadjuvant Treatment Response among HER2- Patients.

OBJECTIVE: Women with advanced HER2- breast cancer have limited treatment options. Breast MRI functional tumor volume (FTV) is used to predict pathologic complete response (pCR) to improve treatment efficacy. In addition to FTV, background parenchymal enhancement (BPE) may predict response and was explored for HER2- patients in the I-SPY-2 TRIAL. METHODS: Women with HER2- stage II or III breast cancer underwent prospective serial breast MRIs during four neoadjuvant chemotherapy timepoints. BPE was quantitatively calculated using whole-breast manual segmentation. Logistic regression models were systematically explored using pre-specified and optimized predictor selection based on BPE or combined with FTV. RESULTS: A total of 352 MRI examinations in 88 patients (29 with pCR, 59 non-pCR) were evaluated. Women with hormone receptor (HR)+HER2- cancers who achieved pCR demonstrated a significantly greater decrease in BPE from baseline to pre-surgery compared to non-pCR patients (odds ratio 0.64, 95% confidence interval (CI): 0.39-0.92, P = 0.04). The associated BPE area under the curve (AUC) was 0.77 (95% CI: 0.56-0.98), comparable to the range of FTV AUC estimates. Among multi-predictor models, the highest cross-validated AUC of 0.81 (95% CI: 0.73-0.90) was achieved with combined FTV+HR predictors, while adding BPE to FTV+HR models had an estimated AUC of 0.82 (95% CI: 0.74-0.92). CONCLUSION: Among women with HER2- cancer, BPE alone demonstrated association with pCR in women with HR+HER2- breast cancer, with similar diagnostic performance to FTV. BPE predictors remained significant in multivariate FTV models, but without added discrimination for pCR prediction. This may be due to small sample size limiting ability to create subtype-specific multivariate models.

Racial/Ethnic Differences in Sleep Quality among Older Adults: Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) Study.

Background: We assessed cross-sectional differences in sleep quality and risk factors among Asian, Black, Latino, and White participants in the Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) Study. Methods: KHANDLE enrolled community-dwelling adults aged ≥65 years living in northern California. Participants completed a modified Pittsburgh Sleep Quality Index to measure six sleep components and a global sleep score (scored 0-24). Covariates included age, sex, central adiposity, education, income, alcohol consumption, ever smoking, physical activity, and depression. Ordinal logistic regression was used to model sleep component scores across race/ethnic groups. Linear regression was used to assess racial/ethnic differences in global sleep score and the association between risk factors and global sleep score. Results: 1,664 participants with a mean age of 76 (SD=7) and mean global sleep score of 6 (SD=4) were analyzed. Using Latinos as reference (highest average sleep score), Blacks had an average .96 (.37, 1.54) unit higher global sleep score (worse sleep) while Asians [ß: .04 (-.56, .63)] and Whites [ß: .28 (-.29, .84)] did not significantly differ. Compared with Latinos, Blacks and Asians had greater odds of a worse score on the sleep duration component; Blacks and Whites had greater odds of a worse score on the sleep disturbances component; and, Whites had greater odds of a worse score on the medication component. Risk factors for poor sleep did not differ by race/ethnicity except alcohol consumption (interaction P=.04), which was associated with poor sleep in Blacks only. Conclusions: In this cohort, racial/ethnic differences in sleep quality were common.

Cancer and risk of Alzheimer's disease: Small association in a nationwide cohort study.

INTRODUCTION: Small observational studies with short-term follow-up suggest that cancer patients are at reduced risk of Alzheimer's disease (AD) compared to the general population. METHODS: A nationwide cohort study using Danish population-based health registries (1980-2013) with cancer patients (n = 949,309) to identify incident diagnoses of AD. We computed absolute reductions in risk attributed to cancer and standardized incidence rate ratios (SIRs) accounting for survival time, comparing the observed to expected number of AD cases. RESULTS: During up to 34 years of follow-up of cancer survivors, the attributable risk reduction was 1.3 per 10,000 person-years, SIR = 0.94 (95% confidence interval 0.92-0.96). SIRs were similar after stratification by sex, age, and cancer stage, and approached that of the general population for those surviving >10 years. DISCUSSION: Inverse associations between cancer and AD were small and diminished over time. Incidence rates in cancer survivors approached those of the general population, suggesting limited association between cancer and AD risk.

Alzheimer's and Parkinson's Diseases and the Risk of Cancer: A Cohort Study.

Observational studies have shown inverse associations between neurological diseases, particularly dementia, and subsequent cancer risk, but is unknown whether this association is valid or arises from bias. We conducted a Danish nationwide cohort study using population-based health registries (1980-2012). The study included patients with dementia (n = 173,434) and with Parkinson's disease (n = 28,835). We followed patients for 10 years to assess subsequent cancer diagnoses. We computed absolute reduction in cancer risk attributable to dementia or Parkinson's disease (expected minus the observed number of cancer cases divided by the person time) and standardized incidence rate ratios (SIRs) as the observed to expected number of cancers, based on sex-, age-, and calendar year-standardized national incidence rates. During 10 years, the reduction in cancer cases were 79.9 per 10,000 person-years for Alzheimer's disease [SIR = 0.68 (95% CI: 0.66, 0.70)], 74.4 per 10,000 person-years for vascular dementia [SIR = 0.71 (95% CI: 0.67, 0.74)], 55.8 per 10,000 person-years [SIR = 0.77 (95% CI: 0.75, 0.78)] for all-cause dementia, and 4.0 per 10,000 person-years [SIR = 0.98 (95% CI: 0.95, 1.02) for Parkinson's disease. Associations were nearly similar for solid tumors diagnosed at localized, regional, or distant stages. We found an inverse association between dementia and cancer risk, with similar associations when considering only cancers diagnosed at distant stage. The cancer risk varied by type of dementia, with a gradient toward a stronger protective effect associated with Alzheimer's disease and vascular dementia, which may favor a biological explanation. Overall results do not show an inverse association between Parkinson's disease and cancer.

Rate of Memory Change Before and After Cancer Diagnosis.

Importance: Patients with a history of cancer, even nonfatal cancers, have lower subsequent Alzheimer disease incidence. An inverse biological link between carcinogenesis and neurodegeneration has been hypothesized, although survival and detection biases are possible explanations. Objective: To compare long-term memory trajectories before and after incident cancer with memory trajectories of similarly aged individuals not diagnosed with cancer. Design, Setting, and Participants: This population-based cohort study included 14 583 US adults born before 1949 with no cancer history from the Health and Retirement Study. Biennial assessments were performed for up to 16 years from 1998 to 2014. Data analysis was performed from January 8 to October 5, 2018. Exposures: Self-reported physician diagnosis of any cancer (excluding nonmelanoma skin cancer) during follow-up. Main Outcomes and Measures: A composite memory score standardized to a mean (SD) of 0 (1) at baseline was based on immediate and delayed word-list recall and proxy assessments. The rate of memory change among people diagnosed with cancer during follow-up before and after diagnosis was compared with rate of memory change in individuals who remained cancer free during follow-up using linear mixed-effect models with random intercepts and slopes. Results: A total of 14 583 participants were included in the sample (mean [SD] age, 66.4 [10.4] years; 8453 [58.0%] female). The mean (SD) follow-up was 11.5 (5.1) years; 2250 had a cancer diagnosis during follow-up, and 12 333 had no cancer diagnosis during follow-up. The rate of memory decline in the decade before a cancer diagnosis was 10.5% (95% CI, 6.2%-14.9%), which was slower than memory decline in similarly aged cancer-free individuals. For individuals diagnosed at 75 years of age, mean memory function immediately before diagnosis was 0.096 SD units (95% CI, 0.060-0.133 SD units) higher compared with that among similarly aged cancer-free individuals. A new cancer diagnosis was associated with a short-term decline in memory of -0.058 (95% CI, -0.084 to -0.032) SD units compared with memory before diagnosis. After diagnosis, the rate of memory decline was 3.9% (95% CI, 0.9%-6.9%) slower in individuals with cancer than in those without a cancer diagnosis. Conclusions and Relevance: In this study, older individuals who developed cancer had better memory and slower memory decline than did similarly aged individuals who remained cancer free. These findings support the possibility of a common pathologic process working in opposite directions in cancer and Alzheimer disease.