Interrelationship of Sleep Disturbances and Cognitive Status on Mortality.

Sleep disturbances may promote the development and advancement of Alzheimer's disease. Our purpose was to determine if sleep disturbances were associated with earlier mortality while accounting for cognition. The National Alzheimer's Coordinating Center database was used to evaluate mortality risk conferred by sleep, and the Montreal Cognitive Assessment score determined cognitive status. Demographics, sleep disturbances, cognitive status, and comorbid/other neuropsychiatric conditions were examined as predictors of survival time via Cox regression. The sample (N = 31,110) had a median age [interquartile range] of 72 [66, 79] years, MoCA score of 23 [16, 26], and survival time of 106.0 months [104.0,108.0]; 10,278 (33%) died during follow-up; 21% (n = 6461) experienced sleep disturbances. Sleep disturbances impacted survival time depending on cognition, with the greatest effect in transition from normal to cognitive impairment (P < .001). Findings support that sleep disturbances negatively impact survival time, and the impact of sleep disturbances on survival time is interrelated with cognition.

Fish and Shellfish Consumption, Cognitive Health and Mortality from Alzheimer's Disease among US Adults Aged 60 and Older.

BACKGROUND: Relationships of fish-shellfish consumption, cognitive health and mortality from Alzheimer's disease (AD) among US adults aged 60 years and older have not been adequately studied. OBJECTIVES: To determine the relationship of fish-shellfish consumption, cognitive health and mortality from AD in US adults aged 60 years and older. DESIGN, SETTING AND PARTICIPANTS: The data of this cross-sectional study of US adults aged 60 years and older were from the National Nutrition and Health Examination Survey (NHANES) datasets. Frequency of fish-shellfish consumption, its association with subjective cognitive decline (SCD) and AD mortality of these participants between 1999 and 2018 and cognitive assessment scores between 2011 and 2014 were analyzed. MEASUREMENTS AND RESULTS: US adults aged 60 years and older consumed fish-shellfish 1.2 times/week and had a blood Hg of 1.63 ug/L on average between 1999 and 2018. Participants aged 60 years and older in the highest quartile of fish-shellfish consumption (~3 times/week) had significantly higher cognitive assessment scores than those in the lowest quartile (rare or no fish-shellfish consumption). Adults in the highest quartile of fish-shellfish consumption had a 30% lower risk (odds ratio 0.7, 95%CI 0.57-0.87) of SCD, and 44% lower risk (hazard ratio 0.56, 95%CI 0.35-0.9) of AD mortality than those in the lowest quartile. CONCLUSION: Increased fish-shellfish consumption was associated with improved scores of cognitive assessment and reduced risks of SCD and AD mortality.

Cognitive Function, Healthy Lifestyle, and All-Cause Mortality among Chinese Older Adults: A Longitudinal Prospective Study.

BACKGROUND: Both cognitive decline and unhealthy lifestyles have been linked to an elevated risk of mortality in older people. We aimed to investigate whether a healthy lifestyle might modify the association between cognitive function and all-cause mortality in Chinese older populations. METHODS: The final analysis included 5124 individuals free of dementia, selected from the Chinese Longitudinal Healthy Longevity Survey from 2011 to 2018. Cognitive function was assessed in 2011 using the Mini-Mental State Examination (MMSE). A lifestyle score was calculated based on five lifestyle factors, including smoking, alcohol consumption, physical activity, diet, and body mass index. Cox proportional hazards models were performed to evaluate the association between baseline cognitive function and the risk of all-cause mortality, with an interaction term of cognitive function and lifestyle score being added to the models. RESULTS: The average age of participants was 81.87 years old at baseline. During a median follow-up of 6.4 years, 1461 deaths were documented. Both higher cognitive function (HR: 0.96; 95% CI: 0.96-0.97) and a healthier lifestyle (HR: 0.92; 95% CI: 0.87-0.97) were significantly associated with a reduced risk of mortality. We found that lifestyle significantly modified the association of cognitive function with mortality (p for interaction = 0.004). The inverse relation between cognitive function and mortality was found to be more pronounced among participants with a healthier lifestyle. Of note, among the lifestyle scores component, diet showed a significant interaction with mortality (p for interaction = 0.003), and the protective HR of the all-cause mortality associated with higher MMSE scores was more prominent among participants with healthy diets compared with unhealthy diets. CONCLUSIONS: Our study indicates that cognitive decline is associated with a higher risk of mortality, and such associations are attenuated by maintaining a healthy lifestyle, with a particular emphasis on healthy diet.

Trajectories of sleep duration and quality and their association with mild cognitive impairment, frailty, and all-cause mortality.

OBJECTIVES: To identify longitudinal trajectories of sleep duration and quality and estimate their association with mild cognitive impairment, frailty, and all-cause mortality. METHODS: We used data from three waves (2009, 2014, 2017) of the WHO Study on Global Aging and Adult Health in Mexico. The sample consisted of 2722 adults aged 50 and over. Sleep duration and quality were assessed by self-report. Sleep trajectories were determined by applying growth mixture models. Mixed-effects logistic (mild cognitive impairment) and ordinal logistic (frailty), and Cox proportional hazards (all-cause mortality) models were fitted. RESULTS: Three classes for sleep duration ("optimal-stable," "long-increasing," and "short-decreasing") and quality ("very good-increasing," "very good-decreasing," and "moderate/poor stable") were identified. Compared to the optimal-stable group, the long-increasing trajectory had greater odds for mild cognitive impairment (odds ratio=1.68, 95% CI: 1.01-2.78) and frailty (odds ratio=1.66, 95% CI: 1.13-2.46), and higher risk for all-cause mortality (hazard ratio=1.91, 95% CI: 1.14-3.19); and the short-decreasing class had a higher probability of frailty (odds ratio=1.83, 95% CI: 1.26-2.64). Regarding the sleep quality, the moderate/poor stable trajectory had higher odds of frailty (odds ratio=1.71, 95% CI: 1.18-2.47) than very good-increasing group. CONCLUSIONS: These results have important implications for clinical practice and public health policies, given that the evaluation and treatment of sleep disorders need more attention in primary care settings. Interventions to detect and treat sleep disorders should be integrated into clinical practice to prevent or delay the appearance of alterations in older adults' physical and cognitive function. Further research on sleep quality and duration is warranted to understand their contribution to healthy aging.

Mortality Risks and Causes of Death by Dementia Types in a Japanese Cohort with Dementia: NCGG-STORIES.

BACKGROUND: Prognosis-related information regarding dementia needs to be updated, as changes in medical and long-term care environments for patients with dementia in recent decades may be improving the prognosis of the disease. OBJECTIVE: We aimed to investigate the mortality, cause of death, and prognostic factors by types of dementia in a Japanese clinic-based cohort. METHODS: The National Center for Geriatrics and Gerontology-Life Stories of People with Dementia consists of clinical records and prognostic data of patients who visited the Memory Clinic in Japan. Patients who attended the clinic between July 2010 and September 2018, or their close relatives, were asked about death information via a postal survey. A cohort of 3,229 patients (mean age, 76.9; female, 1,953) was classified into six groups: normal cognition (NC), mild cognitive impairment (MCI), Alzheimer's disease (AD), vascular dementia, dementia with Lewy bodies (DLB), and frontotemporal lobar degeneration. A Cox proportional hazards model was employed to compare the mortality of each type of dementia, MCI, and NC. RESULTS: Patients with all types of dementia and MCI had higher mortality rates than those with NC (hazard risks: 2.61-5.20). The most common cause of death was pneumonia, followed by cancer. In the MCI, AD, and DLB groups, older age, male sex, and low cognitive function were common prognostic factors but not presence of apolipoprotein E ɛ4 allele. CONCLUSION: Our findings suggest important differences in the mortality risk and cause of death among patients with dementia, which will be useful in advanced care planning and policymaking.

The impact of postoperative cognitive impairment on mid-term survival after heart transplantation.

BACKGROUND: Heart transplantation is the definitive therapy for patients with end-stage heart failure. Antecedent studies reported that a substantial proportion of heart transplant recipients developed postoperative cognitive impairment in the long term. However, no studies have explored the association between postoperative cognitive impairment and survival after heart transplantation. METHODS: The data of 43 adult patients who underwent heart transplantation were consecutively enrolled and assessed using the MMSE and MoCA neuropsychological tests. Kaplan-Meier curves and Cox proportional hazards models were used for survival analyses. Primary component analysis was performed to integrate MoCA subtests into the "Attention factor," "Naming factor," and "Orientation factor." RESULTS: About 30% of the patients were diagnosed with short-term postoperative cognitive impairment. The impairment group was older and had lower baseline cognitive performances, larger LV diameter, worse MMSE decline and higher ratio of significant MoCA decline. Postoperative cognitive impairment was significantly associated with worse survival (P = .028). Multivariate Cox analyses showed that higher postoperative MoCA score was significantly associated with lower mid-term post-transplant mortality (HR = .744 [.584, .949], P = .017), in which "Attention factor" contributed to this association most (HR = .345 [.123, .970], P = .044) rather than "Naming factor" or "Orientation factor." Notably, preoperative cognitive impairment was closely related with postoperative cognitive impairment and also indicated the worse post-transplant survival (P = .015). CONCLUSION: Postoperative as well as preoperative cognitive impairments were associated with a worse mid-term survival after heart transplantation, indicating that neuropsychological assessments before and after heart transplantation should be routinely performed for heart transplant recipients for better risk stratification.

Joint effect of cognitive function and C-reactive protein on all-cause mortality risk: 1999-2002 NHANES.

PURPOSE: Examine the joint effect of cognitive function and C-reactive protein (CRP) on all-cause mortality risk in older U.S. adults. METHODS: Sample included 1335 older adult (≥60 years of age) participants in the 1999-2002 National Health and Nutrition Examination Survey. A four-level variable was created using cognitive function and CRP concentration. Mortality was assessed using National Center for Health Statistics linked death records from the National Death Index. RESULTS: Increased risk of all-cause mortality was revealed in adults with high CRP and low cognitive function and in those with low to average CRP and low cognitive function (P < .0001 for both). Sex-stratified analyses revealed increased all-cause mortality risk in males with low cognitive function, independent of CRP concentration. However, in females, a significant increase in all-cause mortality risk was only observed in those with low to average CRP and low cognitive function. CONCLUSIONS: Low cognitive function was associated with increased all-cause mortality risk independent of CRP concentration. However, the joint effect of cognitive function and CRP on all-cause mortality risk differed according to sex.

Association of cognitive function with increased risk of cancer death and all-cause mortality: Longitudinal analysis, systematic review, and meta-analysis of prospective observational studies.

BACKGROUND: Disturbed cognitive function is associated with several causes of mortality; however, the association between cognitive function and the risk of cancer death has not been extensively investigated yet. We aimed to evaluate the association of cognitive function with the risk of cancer death and all-cause mortality in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) and Leiden 85-plus Study. Additionally, a systematic review and meta-analysis of longitudinal studies were conducted to evaluate the association of cognitive function and risk of cancer death. METHODS: Risk of cancer death and all-cause mortality were reported using hazard ratios (HRs) with 95% confidence interval (CI) in tertiles of cognitive function of PROSPER and Leiden85-Plus Study. Additionally, PubMed, Embase, Web of Science, Cochrane, PsycINFO, Academic Search Premier, CINHAL, and Emcare were searched up to November 1st, 2020 to perform a systematic review and meta-analysis. The relative risks (RRs) with 95%CI of cancer death per each standard deviation lower performance in cognitive measurements were calculated. RESULTS: Participants of PROSPER had 1.65-fold (95%CI 1.11-2.47) greater risk of cancer death (P for trend = 0.016) and 1.85-fold (95%CI 1.46-2.34) higher risk of all-cause mortality (P for trend<0.001), in multivariable models. Results of the Leiden-85 Plus Study showed that subjects with MMSE score below 24 had a lower chance of cancer death (HR 0.79, 95%CI 0.36-1.70, P for trend = 0.820) but had 2.18-fold (95%CI 1.57-3.02) higher risk of all-cause mortality compared to the reference group (P for trend<0.001). Besides, the results of systematic review and meta-analysis showed that per each standard deviation lower performance in cognitive function, individuals were at a 10% higher chance of cancer death (RR 1.10, 95%CI 1.00-1.20, P-value = 0.044). CONCLUSIONS: Lower cognitive function performance is associated with a marginally increased risk of cancer death, in line with a significantly greater risk of all-cause mortality.

Similar mortality risk in incident cognitive impairment and dementia: Evidence from the ASPirin in Reducing Events in the Elderly (ASPREE) trial.

BACKGROUND: This study examined the risk of mortality in older adults with newly detected cognitive impairment or dementia. METHODS: Data from the Australian cohort of the ASPirin in Reducing Events in the Elderly (ASPREE) trial were examined. The ASPREE clinical trial compared daily low-dose aspirin to a placebo and involved 16,703 individuals aged 70 years and over, who were without major cognitive impairment, physical disability, or cardiovascular disease at recruitment. During the trial, evidence of cognitive impairment, based on cognitive testing and medical record information, triggered dementia adjudication of participants using DSM-IV criteria. Cox proportional hazard models were used to compare mortality rates across the dementia, trigger-only, and no-trigger groups. RESULTS: Over a median 4.7-year follow-up period, 806 participants triggered dementia adjudication, with 485 (60.2%) judged to have dementia. Following recruitment, mortality risks were 32.9, 33.6, and 10.8 events per 1000 person-years in the dementia, trigger-no-dementia, and no-trigger groups, respectively. In the fully adjusted model, mortality risks remained higher in the dementia and trigger-no-dementia groups, with hazard ratios of 1.7 (95% CI: 1.3-2.1) and 1.9 (95% CI: 1.5-2.6), respectively. There was no discernible difference between the dementia and trigger-no-dementia groups in mortality rates following recruitment, or following a dementia trigger. These two groups were more likely to die from sepsis, respiratory disease, and dementia, but less likely to die from cancer than the no-trigger group, χ2  = 161.5, p < 0.001. CONCLUSION: ASPREE participants who triggered for a dementia evaluation experienced a substantially higher mortality rate than those who remained cognitively intact. The increase was indistinguishable among persons who met DSM-IV criteria for dementia vs. those who triggered for a dementia evaluation but failed to meet DSM-IV criteria. Future work should investigate whether earlier detection of cognitive decline can be used to identify and prevent early mortality.

Synergistic Impact of Body Mass Index and Cognitive Function on All-Cause Mortality in Older Adults: A Nationwide Longitudinal Study.

Background: Body mass index (BMI) and cognitive function are independent predictors of mortality risk. However, little is known about the combined impact of BMI and cognitive function on the risk of all-cause mortality in older adults. In this study, we aimed to examine the associations between BMI, cognitive function, and all-cause mortality, including between-factor interactions, in the general population of older adults in China. Methods: We used the data between 2011 and 2018 from the Chinese Longitudinal Healthy Longevity Survey that included adults aged ≥65 years residing in the 23 provinces of China. The association between BMI and cognitive function on all-cause mortality was examined with the Cox proportional hazards regression model. Results: The study included 8,293 Chinese older adults. Low BMI (underweight) and cognitive impairment were associated with the highest risk of death after adjustments [hazard ratio (HR) = 2.18; 95% confidence interval (CI), 1.96-2.41]; this combined effect was more prominent among adults aged <100 years and women. In addition, there was an interaction effect of BMI and cognitive impairment on all-cause mortality (P <0.001). Concurrently, among older adults with normal cognition, the risk of mortality related to underweight was higher than among their cognitively impaired counterparts [55% (normal cognition) vs. 38% (cognitive impairment)]. Conclusions: Low BMI (underweight) and cognitive impairment were independently and jointly associated with increased risk of all-cause mortality among Chinese older adults, and females showed a stronger effect in this association. The association between BMI and mortality was more pronounced in the participants with normal cognition than in their cognitively impaired counterparts.

Cognitive Impairment after Lacunar Stroke and the Risk of Recurrent Stroke and Death.

INTRODUCTION: Patients with poststroke cognitive impairment appear to be at higher risk of recurrent stroke and death. However, whether cognitive impairment after lacunar stroke is associated with recurrent stroke and death remains unclear. We assessed whether global or domain-specific cognitive impairment after lacunar stroke is associated with recurrent stroke and death. METHODS: We considered patients from the Secondary Prevention of Small Subcortical Strokes (SPS3) trial with a baseline cognitive exam administered in English by certified SPS3 personnel, 14-180 days after qualifying lacunar stroke. We considered a baseline score of ≤86 on the Cognitive Assessment Screening Instrument to indicate global cognitive impairment, <10 on the Clock Drawing on Command test to indicate executive function impairment, and domain-specific summary scores in the lowest quartile to indicate memory and nonmemory impairment. We used Cox proportional hazards models to estimate the association between poststroke cognitive impairment and subsequent risk of recurrent stroke and death. RESULTS: The study included 1,528 participants with a median enrollment time of 62 days after qualifying stroke. During a mean follow-up of 3.9 years, 11.4% of participants had recurrent stroke and 8.2% died. In the fully adjusted models, memory impairment was independently associated with an increased risk of recurrent stroke (hazard ratio, 1.48; 95% confidence interval [95% CI]: 1.04-2.09) and death (hazard ratio, 1.87; 95% CI: 1.25-2.79). Global impairment (hazard ratio, 1.66; 95% CI: 1.06-2.59) and nonmemory impairment (hazard ratio, 1.74; 95% CI: 1.14-2.67) were associated with an increased risk of death. DISCUSSION/CONCLUSION: After lacunar stroke, memory impairment was an independent predictor of recurrent stroke and death, while global and nonmemory impairment were associated with death. Cognitive screening in lacunar stroke may help identify populations at higher risk of recurrent stroke and death.

Long-term Effects of Cholinesterase Inhibitors on Cognitive Decline and Mortality.

OBJECTIVE: To investigate whether cholinesterase inhibitors (ChEIs) are associated with slower cognitive decline in Alzheimer dementia and decreased risk of severe dementia or death. METHODS: Patients with Alzheimer dementia from the Swedish Dementia Registry starting on ChEIs within 3 months of the dementia diagnosis were included and compared to nontreated patients with Alzheimer dementia. In a propensity score-matched cohort, the association between ChEI use and cognitive trajectories assessed by Mini-Mental State Examination (MMSE) scores was examined with a mixed model, and severe dementia (MMSE score <10) or death as an outcome was assessed with Cox proportional hazards models. RESULTS: The matched cohort included 11,652 ChEI users and 5,826 nonusers. During an average of 5 years of follow-up, 255 cases developed severe dementia, and 6,055 (35%) died. ChEI use was associated with higher MMSE score at each visit (0.13 MMSE points per year; 95% confidence interval [CI] 0.06-0.20). ChEI users had a 27% lower risk of death (0.73, 95% CI 0.69-0.77) compared with nonusers. Galantamine was associated with lower risk of death (0.71, 95% CI 0.65-0.76) and lower risk of severe dementia (0.69, 95% CI 0.47-1.00) and had the strongest effect on cognitive decline of all the ChEIs (0.18 MMSE points per year, 95% CI 0.07-0.28). CONCLUSIONS: ChEIs are associated with cognitive benefits that are modest but persist over time and with reduced mortality risk, which could be explained partly by their cognitive effects. Galantamine was the only ChEI demonstrating a significant reduction in the risk of developing severe dementia. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for patients with Alzheimer dementia ChEIs decrease long-term cognitive decline and risk of death and that galantamine decreases the risk of severe dementia.

Early weight instability is associated with cognitive decline and poor survival in amyotrophic lateral sclerosis.

OBJECTIVE: Our aim was to measure the monthly rate of weight loss during 6 months prior to a diagnosis of amyotrophic lateral sclerosis (ALS) and to explore the effect on prognosis. METHODS: We enrolled 522 patients free from eating difficulties and with short diagnostic delay between June 2014 to June 2019. The calculating formula for the monthly rate of weight loss=[(weight at baseline-weight at diagnosis)/(weight at baseline*100 %)]/time interval. We employed logistic regression analysis to reveal any association between weight loss and cognitive dysfunction. Survival analysis was performed using the Kaplan-Meier curves and Cox proportional hazard models. RESULTS: Weight loss was observed in 272 patients (52.1 %). Patients with severe weight loss had an older age of onset, a lower ALS Functional Rating Scale-Revised score, a faster disease progression rate, and higher frequencies of executive dysfunction and cognitive decline. The monthly rate of weight loss was associated with executive dysfunction and cognitive decline after adjusting for the emotional state. The stratified monthly rate of weight loss was strongly and independently related to ALS survival after adjusting for confounding factors (HR = 1.473, P trend<0.001). Each upper ladder of the rate of weight loss was correlated with worse survival and a 47.3 % (95 % CI: 25.0-73.6 %) increased risk of mortality. CONCLUSIONS: Weight loss is very common in patients with ALS and is associated with poor survival. It is also associated with executive dysfunction and cognitive decline. An important mechanism of weight loss in the early stage of this disease may be hypermetabolism.

Outcomes of transcatheter aortic valve replacement in patients with cognitive dysfunction.

IMPORTANCE: The impact of pre-existing cognitive dysfunction on outcomes after transcatheter aortic valve replacement (TAVR) remains unclear. OBJECTIVE: To study the association between dementia and post-TAVR outcomes. DESIGN: Cohort study with propensity-score matching was conducted using the Nationwide Inpatient Sample. EXPOSURES: History of dementia at the time of undergoing TAVR. MAIN OUTCOMES: All-cause in-hospital mortality, stroke, bleeding requiring transfusion, acute kidney injury, post-procedural vascular complications, post-procedural pacemaker implantation, length of stay, in-hospital delirium, and discharge disposition in patients with and without dementia undergoing TAVR. RESULTS: Of 57,805 patients undergoing TAVR, 2910 (5.0%) had a diagnosis of dementia. Propensity-score matching yielded 2895 matched pairs of patients. TAVR was associated with an increased risk of bleeding requiring transfusion (14.7% vs 8.6%, odd ratio (OR) 1.82 [95% confidence interval (CI) 1.26-2.63]; p < 0.01), discharge to a rehabilitation facility (45.8% vs 31.6%, OR 2.27 [95% CI 1.67-3.08]; p < 0.001), in-hospital delirium (7.4% vs 3.6%, OR 2.13 [95% CI 1.26-3.61]; p < 0.01), increased length of stay (6.75 ± 0.07 days vs 6.11 ± 0.06 days, slope = 1.11 [95% CI 1.03-1.19]; p < 0.01), but comparable in-hospital mortality (2.1% vs 2.6%, OR 1.26 [95% CI 0.57-2.79]; p = 0.57] in patients with dementia compared with patients without dementia. CONCLUSIONS AND RELEVANCE: This study found that patients with dementia undergoing TAVR had a longer hospital stay as well as higher rates of discharge to a rehabilitation facility and in-hospital delirium, which may indicate debility and functional decline during hospitalization; however, in-hospital mortality and other outcomes were comparable between the two groups. TAVR candidates should be subjected to a comprehensive geriatric and cognitive assessment to help risk-stratify them for potential post-procedural functional decline. Prospective studies aimed at standardizing cognitive scoring and evaluating the post-procedural quality of life are needed.

Molecular Subtyping of Mild Cognitive Impairment Based on Genetic Polymorphism and Gene Expression.

BACKGROUND: Alzheimer's Disease (AD) is a neurodegenerative brain disease in the elderly. Recent studies have revealed the heterogeneous nature of AD. Mild Cognitive Impairment (MCI) is the prodromal stage of AD. OBJECTIVES: In this study, we identified subtypes of MCI based on genetic polymorphism and gene expression. METHODS: We utilized the two types of omics data, namely genetic polymorphism and gene expression profiling, derived from 125 MCI patients' peripheral blood samples from the ADNI-1 dataset. Similarity network fusion (SNF) algorithm was implemented to cluster MCI patient subtypes. And 185 MCI patients in ADNI-2 were utilized to evaluate the effectiveness of this method. Two MCI subtypes were identified by implementing the SNF algorithm. RESULTS: We used Kaplan-Meier analysis and log-rank testing for the conversion from MCI to AD between two subtypes, and p-value is 4.58×10-3. In addition, we compared patients among two MCI subtypes by the following factors: the changes in Alzheimer's Disease cognitive scales and MRI image; significantly enriched pathways based on differentially expressed genes. This study proved that MCI is a heterogeneous disease by concluding that AD development in two MCI subtypes is significantly different. CONCLUSIONS: MCI patients with different molecular characteristics have different risks converting to AD. In addition to evaluating statistics, genetic polymorphism and gene expression profiling from MCI patients' peripheral blood are non-invasiveness and cost-effectiveness markers to identify MCI subtypes for clinical application.

Different Cognitive Profiles Are Associated with Progression Rate and Age at Death in Probable Alzheimer's Disease.

BACKGROUND: Cognitive profiles characterized by primarily language or visuospatial deficits have been documented in individuals meeting diagnostic criteria for probable Alzheimer's disease (AD), but their association with progression rate or overall survival is not well described. OBJECTIVE: To compare time from diagnosis to severe disease stage and death in probable AD patients classified into three groups based on neuropsychological test performance: marked verbal impairment (Verb-PI) with relatively preserved visuospatial function, marked visuospatial impairment with preserved verbal function (Vis-PI), and balanced verbal and visuospatial impairments (Bal-PI). METHODS: This prospective cohort study included 540 probable AD patients attending an academic memory clinic who were enrolled from 1995-2013 and followed annually. Eligible individuals had a Mini-Mental State Exam (MMSE) score ≥10 at baseline, and at least one annual follow up visit. We used Cox proportional hazards modeling to analyze the association of cognitive profiles with time to decline in MMSE and CDR Global Score. RESULTS: Sixty-one (11.3%) individuals had a Verb-PI profile, 86 (16%) had a Vis-PI profile, and 393 (72.8%) a Bal-PI profile. MMSE decline to <10 was faster in Verb-PI than Vis-PI (HR 2.004, 95%CI, 1.062-3.780; p = 0.032). Progression to CDR-GS = 3 was faster in Verb-PI individuals compared to Bal-PI (HR 1.604, 95%CI, 1.022-2.515; p = 0.040) or Vis-PI (HR 2.388, 95%CI, 1.330-4.288; p = 0.004) individuals. Baseline cognitive profile did not affect mortality. CONCLUSION: A recognition of different AD profiles may help to personalize care by providing a better understanding of pathogenesis and expected progression.

Neurocognitive status and risk of mortality among people living with human immunodeficiency virus: an 18-year retrospective cohort study.

HIV-related neurocognitive impairment (NCI) may increase the risk of death. However, a survival disadvantage for patients with NCI has not been well studied in the post-combination antiretroviral therapy (cART) era. Specifically, limited research has been conducted considering the reversible nature and variable progression of the impairment and this area demands further evaluation. We performed multivariable Cox proportional hazards modeling to assess the association between baseline NCI (global T scores) and mortality. A joint modeling approach was then used to model the trajectory of global neurocognitive functioning over time and the association between neurocognitive trajectory and mortality. Among the National NeuroAIDS Tissue Consortium's (NNTC) HIV-infected participants, we found a strong negative association between NCI and mortality in the older age groups (e.g., at age = 55, HR = 0.79; 95% CI 0.64-0.99). Three neurocognitive sub-domains (abstraction and executive functioning, speed of information processing, and motor) had the strongest negative association with mortality. Joint modelling indicated a 33% lower hazard for every 10-unit increase in global T scores (HR = 0.67; 95% CI 0.56-0.80). The study identified older HIV-infected individuals with NCI as a group needing special attention for the longevity of life. The study has considerable prognostic utility by not only predicting mortality hazard, but also future cognitive status.

Place of Death for Persons With and Without Cognitive Impairment in the United States.

BACKGROUND/OBJECTIVES: There is increasing recognition that place of death is an important component of quality of end-of-life care (EOLC) and quality of death. This study examined where older persons with and without cognitive impairment die in the United States, what factors contribute to place of death, and whether place of death influences satisfaction with EOLC. DESIGN: Cross-sectional secondary data analysis. SETTING: In-person interviews with community-dwelling proxy respondents. PARTICIPANTS: Data were collected from 1,500 proxies for deceased participants in the National Health and Aging Trends Study (NHATS), a nationally-representative sample of community-dwelling Medicare beneficiaries aged 65 and older. MEASUREMENTS: Study variables were obtained from the NHATS "last month of life" interview data. Survey weights were applied to all analyses. RESULTS: Persons with cognitive impairment (CI) most often died at home, while cognitively healthy persons (CHP) were equally likely to die at home or in a hospital. Persons with CI who utilized the Medicare Hospice Benefit were 14.5 times more likely to die at home than in a hospital, and 3.4 times more likely to die at home than a nursing home. CHP who use this benefit were over six times more likely to die at home than in a hospital, and more than twice as likely to die at home than a nursing home. Place of death for CHP was also associated with age and race. Proxies of persons with CI who died at home rated EOLC as more favorable, while proxies of CHP rated in-home and hospital care equally. CONCLUSION: Findings add to the scant literature identifying factors associated with place of death for older adults with and without CI and results suggest that place of death is a quality of care indicator for these populations. These findings may inform EOLC planning and policy-making and facilitate greater well-being at end-of-life.

Multimorbidity patterns and their relationship to mortality in the US older adult population.

BACKGROUND: Understanding patterns of multimorbidity in the US older adult population and their relationship with mortality is important for reducing healthcare utilization and improving health. Previous investigations measured multimorbidity as counts of conditions rather than specific combination of conditions. METHODS: This cross-sectional study with longitudinal mortality follow-up employed latent class analysis (LCA) to develop clinically meaningful subgroups of participants aged 50 and older with different combinations of 13 chronic conditions from the National Health Interview Survey 2002-2014. Mortality linkage with National Death Index was performed through December 2015 for 166,126 participants. Survival analyses were conducted to assess the relationships between LCA classes and all-cause mortality and cause specific mortalities. RESULTS: LCA identified five multimorbidity groups with primary characteristics: "healthy" (51.5%), "age-associated chronic conditions" (33.6%), "respiratory conditions" (7.3%), "cognitively impaired" (4.3%) and "complex cardiometabolic" (3.2%). Covariate-adjusted survival analysis indicated "complex cardiometabolic" class had the highest mortality with a Hazard Ratio (HR) of 5.30, 99.5% CI [4.52, 6.22]; followed by "cognitively impaired" class (3.34 [2.93, 3.81]); "respiratory condition" class (2.14 [1.87, 2.46]); and "age-associated chronic conditions" class (1.81 [1.66, 1.98]). Patterns of multimorbidity classes were strongly associated with the primary underlying cause of death. The "cognitively impaired" class reported similar number of conditions compared to the "respiratory condition" class but had significantly higher mortality (3.8 vs 3.7 conditions, HR = 1.56 [1.32, 1.85]). CONCLUSION: We demonstrated that LCA method is effective in classifying clinically meaningful multimorbidity subgroup. Specific combinations of conditions including cognitive impairment and depressive symptoms have a substantial detrimental impact on the mortality of older adults. The numbers of chronic conditions experienced by older adults is not always proportional to mortality risk. Our findings provide valuable information for identifying high risk older adults with multimorbidity to facilitate early intervention to treat chronic conditions and reduce mortality.

Correlates of cognitive impairment in adult cancer survivors who have received chemotherapy and report cognitive problems.

OBJECTIVE: Cognitive impairment negatively affects some cancer survivors who have completed chemotherapy; however, factors underlying this cognitive impairment remain poorly understood. We aimed to investigate (1) the relative importance of demographics, medical, and psychological characteristics associated with cognitive impairment and (2) the specific variables associated with cognitive impairment in adult cancer survivors who completed adjuvant chemotherapy. METHODS: We performed post hoc analyses of baseline data from early-stage cancer survivors with cognitive complaints who received adjuvant chemotherapy 0.5-5 years earlier and volunteered for a trial designed to improve cognition. The primary outcome of self-reported cognitive impairment was measured using a questionnaire; secondary outcome of objective cognitive impairment was measured using a computerized neuropsychological test battery. Hierarchical linear regression determined the relative importance of demographics, medical, and psychological characteristics in associations with both self-reported and objective cognitive impairment. RESULTS: The sample was 95% female and 89% breast cancer patients. The final model accounted for 33% of variation in self-reported cognitive impairment (n = 212, demographics 5%, medical 3%, and psychological 25%), with fatigue and stress as significant individual correlates (p values ≤ 0.0001). For the secondary analysis, the final model accounted for 19% of variation in objective cognitive impairment (n = 206, demographics 10%, medical 5%, and psychological 4%), with age, smoking history, and number of chemotherapy cycles as significant individual correlates. CONCLUSION: We found that psychological characteristics are more important than demographic and medical characteristics in self-reported cognitive impairment, whereas other characteristics are more important in objective cognitive impairment. This suggests clinicians should investigate possible psychological problems in cancer survivors who self-report cognitive impairment.