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.

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.

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.

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.

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.

Cognitive impairment three months after surgery is an independent predictor of survival time in glioblastoma patients.

PURPOSE: Cognitive functioning is increasingly investigated for its prognostic value in glioblastoma (GBM) patients, but the association of cognitive status during early adjuvant treatment with survival time is unclear. The aim of this study was to determine whether cognitive performance three months after surgical resection predicted survival time, while using a clinically intuitive time ratio (TR) statistic. METHODS: Newly diagnosed patients with GBM undergoing resection between November 2010 and February 2018 completed computerized cognitive assessment 3 months after surgery with the CNS Vital Signs battery (8 measures). The association of cognitive performance (continuous Z scores and dichotomous impairment status; impaired vs. unimpaired) with survival time was assessed with multivariate Accelerated Failure Time (AFT) models that also included clinical prognostic factors and covariates related to cognitive performances. RESULTS: 114 patients were included in the analyses (median survival time 16.4 months). Of the clinical factors, postoperative Karnofsky Performance Status (TR 1.51), surgical (TR 2.20) and non-surgical (TR 1.94) salvage treatment, and pre-surgical tumor volume (cm3, TR 1.003) were significant independent predictors of survival time. Independently of the base model factors and covariates, impairment on Stroop test I and Stroop test III estimated 23% and 26% reduction of survival time (TR 0.77, TR 0.74) respectively, as compared to unimpaired performance. CONCLUSION: These findings suggest that impaired performances on tests of executive control and processing speed in the early phase of adjuvant treatment can reflect a worse prognostic outlook rather than an early treatment effect, and their assessment might allow for early refinement of current prognostic stratification.

Association of Cognitive Impairment With Treatment and Outcomes in Older Myocardial Infarction Patients: A Report From the NCDR Chest Pain-MI Registry.

Background Little is known regarding use of cardiac therapies and clinical outcomes among older myocardial infarction (MI) patients with cognitive impairment. Methods and Results Patients ≥65 years old with MI in the NCDR (National Cardiovascular Data Registry) Chest Pain-MI Registry between January 2015 and December 2016 were categorized by presence and degree of chart-documented cognitive impairment. We evaluated whether cognitive impairment was associated with all-cause in-hospital mortality after adjusting for known prognosticators. Among 43 812 ST-segment-elevation myocardial infarction (STEMI) patients, 3.9% had mild and 2.0% had moderate/severe cognitive impairment; among 90 904 non-ST-segment-elevation myocardial infarction (NSTEMI patients, 5.7% had mild and 2.6% had moderate/severe cognitive impairment. A statistically significant but numerically small difference in the use of primary percutaneous coronary intervention was observed between patients with STEMI with and without cognitive impairment (none, 92.1% versus mild, 92.8% versus moderate/severe, 90.4%; P=0.03); use of fibrinolysis was lower among patients with cognitive impairment (none, 40.9% versus mild, 27.4% versus moderate/severe, 24.2%; P<0.001). Compared with NSTEMI patients without cognitive impairment, rates of angiography, percutaneous coronary intervention, and coronary artery bypass grafting were significantly lower among patients with NSTEMI with mild (41%, 45%, and 70% lower, respectively) and moderate/severe cognitive impairment (71%, 74%, and 93% lower, respectively). After adjustment, compared with no cognitive impairment, presence of moderate/severe (STEMI: odds ratio, 2.2, 95% CI, 1.8-2.7; NSTEMI: odds ratio, 1.7, 95% CI, 1.4-2.0) and mild cognitive impairment (STEMI: OR, 1.3, 95% CI, 1.1-1.5; NSTEMI: odds ratio, 1.3, 95% CI, 1.2-1.5) was associated with higher in-hospital mortality. Conclusions Patients with NSTEMI with cognitive impairment are substantially less likely to receive invasive cardiac care, while patients with STEMI with cognitive impairment receive similar primary percutaneous coronary intervention but less fibrinolysis. Presence and degree of cognitive impairment was independently associated with increased in-hospital mortality. Approaching clinical decision making for older patients with MI with cognitive impairment requires further study.

How do potentially inappropriate medications and polypharmacy affect mortality in frail and non-frail cognitively impaired older adults? A cohort study.

OBJECTIVES: To test whether the use of potentially inappropriate central nervous system acting medications, proton pump inhibitors (PPIs) or polypharmacy are associated with mortality in cognitively impaired older adults and whether frailer people are at greater risk of harm. SETTING: A cohort study nested within the Cognitive Function and Ageing Study II, a population representative cohort study of the older population in Cambridgeshire, Nottingham and Newcastle, UK. PARTICIPANTS: A total of 1154 cognitively impaired participants, aged 65 years or older. EXPOSURES: Any use of antipsychotics, antidepressants, other anticholinergic medication, benzodiazepines or PPIs, polypharmacy (5-9) and hyperpolypharmacy (≥10 reported medications) were ascertained at baseline. Frailty was assessed using the Fried criteria. PRIMARY OUTCOME: Mortality up to 8 years follow-up. HRs associated with potentially inappropriate medication (PIM), frailty and their interaction were estimated adjusting for covariates. RESULTS: Within the sample, 44% were taking one or more PIM. Apart from antipsychotics (adjusted HR=3.24, 95% CI 1.83 to 5.73), use of specific PIM was not associated with greater subsequent mortality. Polypharmacy (HR=1.17, 95% CI 0.95 to 1.45) and hyperpolypharmacy were associated with mortality (HR=1.60, 95% CI 1.16 to 2.22). Being frail (HR=1.90, 95% CI 1.32 to 2.72) or prefrail (HR=1.56, 95% CI 1.10 to 2.20) was associated with increased mortality. There was some evidence that the HR for polypharmacy on mortality was lower among frailer individuals, but the overall polypharmacy by frailty interaction was not statistically significant (p=0.102). CONCLUSIONS: For those with cognitive impairment, greater concern should be afforded to the number of medications than the prescription of specific classes. Frailer individuals may have a lower relative risk of mortality associated with polypharmacy than less frail individuals.

Cognitive impairment, brain ischemia and shorter telomeres are predictors of mortality in the Japanese elderly: A 13-year prospective community-based study.

OBJECTIVE: To examine whether cognitive impairment, deep white matter hyperintensity (DWMH) on brain MRI, and shorter telomere length would be predictors of mortality in community-dwelling Japanese elderly. METHODS: We followed 259 individuals (74% of all the residents at age 70) from age 70 to 83 years. The mean observation period was 133 ±â€¯34 months. The key clinical characteristics examined included DWMH on brain MRI and cognitive function. Telomere length was also measured in 81 subjects. Both univariate and multivariate analyses were performed. RESULTS: Of the 259 subjects, 69 subjects (30 men, 39 women; 26.6%) died during the follow-up period. Cognitive impairment, smoking habits, diabetes mellitus, and moderate to severe DWMH were significant predictors of total mortality in univariate analysis. However, only cognitive impairment and moderate to severe DWMH remained as significant independent predictors of death in multivariate analysis. The rate of mortality increased with additional number of risk factors (cognitive impairment and DWMH). The total mortality of subjects with both cognitive impairment and DWMH was 71.4%. The median telomere length was 7.8 kb in the deceased and 8.2 kb in the living subjects. The deceased subjects had significantly shorter telomere length (P = .0025) than the living subjects. Telomere length with moderate to severe DWMH was higher than without moderate to severe DWMH on brain MRI (P = .017). CONCLUSIONS: The present study revealed that cognitive impairment, DWMH, and shorter telomere length were significant predictors of total mortality in the community-dwelling Japanese elderly. Furthermore, the combination of cognitive impairment and DWMH increased the mortality rate, as compared with a single risk factor. It is also clarified that a significant difference was present in telomere length by severity of DWMH.

Assessing Risk for Adverse Outcomes in Older Adults: The Need to Include Both Physical Frailty and Cognition.

BACKGROUND: Physical frailty is a powerful tool for identifying nondisabled individuals at high risk of adverse outcomes. The extent to which cognitive impairment in those without dementia adds value to physical frailty in detecting high-risk individuals remains unclear. OBJECTIVES: To estimate the effects of combining physical frailty and cognitive impairment without dementia (CIND) on the risk of basic activities of daily living (ADL) dependence and death over 8 years. DESIGN: Prospective cohort study. SETTING: The Health and Retirement Study (HRS). PARTICIPANTS: A total of 7338 community-dwelling people, 65 years or older, without dementia and ADL dependence at baseline (2006-2008). Follow-up assessments occurred every 2 years until 2014. MEASUREMENTS: The five components of the Cardiovascular Health Study defined physical frailty. A well-validated HRS method, including verbal recall, series of subtractions, and backward count task, assessed cognition. Primary outcomes were time to ADL dependence and death. Hazard models, considering death as a competing risk, associated physical frailty and CIND with outcomes after adjusting for sociodemographics, comorbidities, depression, and smoking status. RESULTS: The prevalence of physical frailty was 15%; CIND, 19%; and both deficits, 5%. In unadjusted and adjusted analyses, combining these factors identified older adults at an escalating risk for ADL dependence (no deficit = 14% [reference group]; only CIND = 26%, sub-hazard ratio [sHR] = 1.5, 95% confidence interval [CI] = 1.3-1.8; only frail = 33%, sHR = 1.7, 95% CI = 1.4-2.0; both deficits = 46%, sHR = 2.0, 95%CI = 1.6-2.6) and death (no deficit = 21%; only CIND = 41%, HR = 1.6, 95% CI = 1.4-1.9; only frail = 56%, HR = 2.2, 95% CI = 1.7-2.7; both deficits = 66%, HR = 2.6, 95% CI = 2.0-3.3) over 8-year follow-up. Adding the cognitive measure to models that already included physical frailty alone increased accuracy in identifying those at higher risk of ADL dependence (Harrell's concordance [C], 0.74 vs 0.71; P < .001) and death (Harrell's C, 0.70 vs 0.67; P < .001). CONCLUSION: Physical frailty and CIND are independent predictors of incident disability and death. Because together physical frailty and CIND identify vulnerable older adults better, optimal risk assessment should supplement measures of physical frailty with measures of cognitive function. J Am Geriatr Soc 67:477-483, 2019.

Poor nutritional status but not cognitive or functional impairment per se independently predict 1 year mortality in elderly patients with hip-fracture.

BACKGROUND & AIMS: Hip fractures are strongly associated with mortality in the elderly. Studies investigating predisposing factors have suggested a negative impact of poor nutritional, cognitive and functional status on patient survival, however their independent prognostic impact as well as their interactions remain undefined. This study aimed to determine whether poor nutritional status independently predicts 1 year post-fracture mortality after adjusting for cognitive and functional status and for other clinically relevant covariates. METHODS: 1211 surgically treated hip fracture elderly (age ≥ 65) patients consecutively admitted to the Orthopaedic Surgery Unit of the "Azienda Sanitaria Universitaria Integrata Trieste" (ASUITs), Cattinara Hospital, Trieste, Italy and managed by a dedicated orthogeriatric team. Pre-admission nutritional status was evaluated by Mini Nutritional Assessment (MNA) questionnaire, cognitive status by Short Portable Mental Status Questionnaire (SPMSQ) and functional status by Activity of Daily Living (ADL) questionnaire. All other clinical data, including comorbidities, type of surgery, post-operative complications (delirium, deep vein thrombosis, cardiovascular complications, infections, need for blood transfusions) were obtained by hospital clinical records and by mortality registry. RESULTS: Poor nutritional status (defined as MNA ≤23.5), increased cognitive and functional impairment were all associated with 3-, 6- and 12 month mortality (p < 0.001). Both cognitive and functional impairment were associated with poor nutritional status (p < 0.001). Logistic regression analysis demonstrated that the association between nutritional status and 3-, 6- and 12- month mortality was independent of age, gender, comorbidities, type of surgery and post-operative complications as well as of cognitive and functional impairment (p < 0.001). In contrast, the associations between mortality and cognitive and functional impairment were independent (p < 0.001) of demographic (age, gender) and clinical covariates but not of malnutrition. Kaplan-Meier analysis showed a lower mean survival time (p < 0.001) in patients with poor nutritional status compared with those well-nourished. CONCLUSIONS: In hip fracture elderly patients, poor nutritional status strongly predicts 1 year mortality, independently of demographic, functional, cognitive and clinical risk factors. The negative prognostic impact of functional and cognitive impairment on mortality is mediated by their association with poor nutritional status.

Postoperative Outcomes in SAVR/TAVR Patients With Cognitive Impairment: A Systematic Review.

To assess the predictive value of preoperative cognitive impairment on postoperative in-hospital, short-term, and mid-term outcomes among patients undergoing surgical or transcatheter aortic valve replacement. The review was conducted according to PRISMA guidelines. Articles were identified in EMBASE, Medline, and PubMed. Eligible articles compared the outcomes of patients with and without preoperative cognitive impairment who underwent aortic valve replacement and were published in English between January 1, 1997 and November 1, 2017. The quality of included observational studies was evaluated using the Newcastle-Ottawa scale. The strength of the body of evidence was also assessed. A total of 6163 abstracts were screened by 2 independent reviewers and 31 full-text articles were reviewed. Eight studies met inclusion criteria. The studies included 1 case-control, 5 prospective cohort, and 2 retrospective cohort studies. Given the paucity and heterogeneity of studies, meta-analysis was not possible. Five studies were of good quality. Preoperative cognitive impairment is a risk factor for postoperative delirium in 2 studies, increased mid-term mortality in 2 studies, and increased length of stay, risk of discharge to a health-care facility or progressive disability in 1 study. However, given the paucity and methodological flaws of the included studies, the body of evidence on the predictive value of preoperative cognitive impairment on postoperative outcomes remains weak. This systematic review highlights the need for more good quality studies to provide evidence regarding the incidence of cognitive impairment and associations with poor outcomes after aortic valve replacement.

Impact of Mild Cognitive Impairment on Mortality and Cause of Death in the Elderly.

BACKGROUND: Mild cognitive impairment (MCI) is a cognitive state that lies on the continuum between normal aging and dementia, and the prevalence of MCI is higher than dementia. However, the risk for mortality of people with MCI has been far less studied than that of people with dementia, and the population attributable risk percent (PAR%) of death attributable to MCI has not been estimated yet. OBJECTIVE: To investigate the impact of MCI on mortality and the cause of death in the elderly, and to estimate the PAR% of deaths attributable to MCI. METHODS: Data came from 7,315 elderly subjects aged ≥60 years without dementia from two cohort studies with diagnostic assessments of MCI at baseline. Deaths among participants were confirmed through the nationwide mortality database of Statistics Korea. RESULTS: MCI increased the risk of mortality in a multivariate Cox proportional model adjusting for age, sex, education, smoking, alcohol drinking, chronic illness, depression, vascular components, and cohort (hazard ratio = 1.59, 95% confidence interval 1.30, 1.94). PAR% of death attributable to MCI was 10.7% for age 65-74 years, 16.0% for age 75-84 years, and 24.2% for age ≥85 years. In the elderly with MCI, mortality risks from cerebrovascular disease, respiratory disease, and external causes were higher than in the cognitively normal elderly. CONCLUSIONS: Our results suggest that the mortality risk of MCI in Asian countries may be comparable to that in Western countries, and MCI can contribute to the death of the elderly as much as dementia.

Estimation of lifetime risks of Alzheimer's disease dementia using biomarkers for preclinical disease.

INTRODUCTION: Lifetime risks are the probabilities of progressing to Alzheimer's disease (AD) dementia during one's lifespan. Here, we report the first estimates of the lifetime and ten-year risks of AD dementia based on age, gender, and biomarker tests for preclinical disease. METHODS: We used a multistate model for the disease process together with US death rates. RESULTS: Lifetime risks of AD dementia vary considerably by age, gender, and the preclinical or clinical disease state of the individual. For example, the lifetime risks for a female with only amyloidosis are 8.4% for a 90-year old and 29.3% for a 65-year old. Persons younger than 85 years with mild cognitive impairment, amyloidosis, and neurodegeneration have lifetime risks of AD dementia greater than 50%. DISCUSSION: Most persons with preclinical AD will not develop AD dementia during their lifetimes. Lifetime risks help interpret the clinical significance of biomarker screening tests for AD.

Addition of the Aß42/40 ratio to the cerebrospinal fluid biomarker profile increases the predictive value for underlying Alzheimer's disease dementia in mild cognitive impairment.

BACKGROUND: Cerebrospinal fluid (CSF) biomarkers have been used to increase the evidence of underlying Alzheimer's disease (AD) pathology in mild cognitive impairment (MCI). However, CSF biomarker-based classification often results in conflicting profiles with controversial prognostic value. Normalization of the CSF Aß42 concentration to the level of total amyloid beta (Aß), using the Aß42/40 ratio, has been shown to improve the distinction between AD and non-AD dementia. Therefore, we evaluated whether the Aß42/40 ratio would improve MCI categorization and more accurately predict progression to AD. METHODS: Our baseline population consisted of 197 MCI patients, of which 144 had a follow-up ≥ 2 years, and comprised the longitudinal study group. To establish our own CSF Aß42/40 ratio reference value, a group of 168 AD-dementia patients and 66 neurological controls was also included. CSF biomarker-based classification was operationalized according to the framework of the National Institute of Aging-Alzheimer Association criteria for MCI. RESULTS: When using the core CSF biomarkers (Aß42, total Tau and phosphorylated Tau), 30% of the patients fell into the high-AD-likelihood (HL) group (both amyloid and neurodegeneration markers positive), 30% into the low-AD-likelihood group (all biomarkers negative), 28% into the suspected non-Alzheimer pathophysiology (SNAP) group (only neurodegeneration markers positive) and 12% into the isolated amyloid pathology group (only amyloid-positive). Replacing Aß42 by the Aß42/40 ratio resulted in a significant increase in the percentage of patients with amyloidosis (42-59%) and in the proportion of interpretable biological profiles (61-75%), due to a reduction by half in the number of SNAP cases and an increase in the proportion of the HL subgroup. Survival analysis showed that risk of progression to AD was highest in the HL group, and increased when the Aß42/40 ratio, instead of Aß42, combined with total Tau and phosphorylated Tau was used for biomarker-based categorization. CONCLUSIONS: Our results confirm the usefulness of the CSF Aß42/40 ratio in the interpretation of CSF biomarker profiles in MCI patients, by increasing the proportion of conclusive profiles and enhancing their predictive value for underlying AD.

Prevalence of Cognitive Impairment and Association With Survival Among Older Patients With Hematologic Cancers.

Importance: As the population ages, cognitive impairment has promised to become increasingly common among patients with cancer. Little is known about how specific domains of cognitive impairment may be associated with survival among older patients with hematologic cancers. Objective: To determine the prevalence of domain-specific cognitive impairment and its association with overall survival among older patients with blood cancer. Design, Setting, and Participants: This prospective observational cohort study included all patients 75 years and older who presented for initial consultation in the leukemia, myeloma, or lymphoma clinics of a large tertiary hospital in Boston, Massachusetts, from February 1, 2015, to March 31, 2017. Patients underwent screening for frailty and cognitive dysfunction and were followed up for survival. Exposures: The Clock-in-the-Box (CIB) test was used to screen for executive dysfunction. A 5-word delayed recall test was used to screen for impairment in working memory. The Fried frailty phenotype and Rockwood cumulative deficit model of frailty were also assessed to characterize participants as robust, prefrail, or frail. Results: Among 420 consecutive patients approached, 360 (85.7%) agreed to undergo frailty assessment (232 men [64.4%] and 128 women [35.6%]; mean [SD] age, 79.8 [3.9] years), and 341 of those (94.7%) completed both cognitive screening tests. One hundred twenty-seven patients (35.3%) had probable executive dysfunction on the CIB, and 62 (17.2%) had probable impairment in working memory on the 5-word delayed recall. Impairment in either domain was modestly correlated with the Fried frailty phenotype (CIB, ρ = 0.177; delayed recall, ρ = 0.170; P = .01 for both), and many phenotypically robust patients also had probable cognitive impairment (24 of 104 [23.1%] on CIB and 9 of 104 [8.7%] on delayed recall). Patients with impaired working memory had worse median survival (10.9 [SD, 12.9] vs 12.2 [SD, 14.7] months; log-rank P < .001), including when stratified by indolent cancer (log-rank P = .01) and aggressive cancer (P < .001) and in multivariate analysis when adjusting for age, comorbidities, and disease aggressiveness (odds ratio, 0.26; 95% CI, 0.13-0.50). Impaired working memory was also associated with worse survival for those undergoing intensive treatment (log-rank P < .001). Executive dysfunction was associated with worse survival only among patients who underwent intensive treatment (log-rank P = .03). Conclusions and Relevance: These data suggest that domains of cognitive dysfunction may be prevalent in older patients with blood cancer and may have differential predictive value for survival. Targeted interventions are needed for this vulnerable patient population.

Preoperative risk evaluation in patients over 75 years candidates to non-cardiac and cardiac surgery.

In the 24th and 25thof June 2016, 80 national experts were invited to Rome from The Italian Society of Geriatric Cardiology and the Italian Association of Cardiovascular Prevention and Rehabilitation to revise the current knowledge on the perioperative risk in the elderly. Cardiologists, geriatricians, heart and general surgeons and anesthesiologists discussed the topic with the objective of reaching a consensus and to launch observational research and registries in the field of perioperative risk evaluation in the elderly. The introduction of objective measures of frailty on top of traditional cardiac evaluation in the different surgical contexts could allow for a more precise definition of "surgical risk", appropriate perioperative management and postoperative outcome.

Cognitive impairment assessed at annual geriatric health examinations predicts mortality among the elderly.

OBJECTIVE: To determine whether cognitive impairment assessed at annual geriatric health examinations is associated with increased mortality in the elderly. METHOD: This cohort study was based on data obtained from the government-sponsored Annual Geriatric Health Examination Program for the elderly in Taipei City between 2006 and 2010. The study sample consisted of 77,541 community-dwelling Taipei citizens aged 65 years or older. The Short Portable Mental Status Questionnaire (SPMSQ) was selected to measure cognitive impairment. Mortality was ascertained by matching cohort IDs with national death files. RESULTS: There was a dose-response relationship between cognitive impairment and mortality (increased one score of SPMSQ, Hazard ratio [HR]: 1.12, 95% confidence interval [CI]: 1.10-1.14). Relative to no cognitive impairment, the HRs were 1.67 (95% CI: 1.43-1.94), 2.26 (95% CI: 1.90-2.70), and 2.68 (95% CI: 2.25-3.19) for mild, moderate, and severe cognitive impairments, respectively. The causes of death associated with cognitive impairment were circulatory, respiratory, and other causes, but not death from cancer. CONCLUSION: Cognitive impairment as measured by the SPMSQ is associated with an increased risk for mortality. Even mild cognitive impairment was associated with greater risk of mortality at a relatively short follow-up time.