Cohort Of Elderly Individuals Research Articles

Subtle postoperative cognitive disorder in preclinical Alzheimer's disease.

We examined the association between preclinical Alzheimer's disease (AD) and undergoing anesthesia and surgery ("surgery" henceforth) in a cohort of elderly individuals with a subjective cognitive decline (SCD). Individuals with SCD (N=268) were enrolled in a longitudinal follow-up study. Participants underwent comprehensive yearly cognitive evaluation for a period of 4years. Brain amyloid load and glucose metabolism were studied by 18F-Florbetapir and Fluorodeoxyglucose positron emission tomography (PET) at baseline and after two years of follow-up. Exposure to surgery was systematically assessed during the first two years of follow-up. The association between surgery, cognition and AD markers was evaluated using generalized linear mixed models for cognition and linear models for neuroimaging markers. Sixty-five participants (24.25%) underwent surgery during the first year of follow-up, and 43 (16.04%) during the second year. Undergoing surgery had no overall impact on cognition over 4years of follow-up nor on amyloid load and brain metabolism at two years of follow-up. However, a second step analysis revealed a small but significant association between undergoing surgery and a subtle decline in executive functions such as mental flexibility and divided attention (TMT B-A), in participants with greater amyloid load at baseline (Cohen's f2=0.01, multiple comparison corrected p<0.001). Highly educated participants with surgery had significantly decreased metabolism over two years, when compared to low educated participants (Cohen's f2=0.04, p=0.031). Our results suggest that surgery is associated with an increased risk of subtle cognitive decline after surgery, in the cognitively healthy elderly at risk for AD.

Aortic Pulse Wave Velocity as Adjunct Risk Marker for Assessing Cardiovascular Disease Risk: Prospective Study.

Aortic pulse wave velocity is a noninvasive measure of aortic stiffness and arterial aging. Its current value in cardiovascular risk estimation practice is unknown. We aimed to establish whether aortic pulse wave velocity identified individuals with higher risk of incident major adverse cardiovascular events and improved performance of the American Heart Association/American College of Cardiology atherosclerotic cardiovascular disease risk score. This prospective analysis included 3837 Whitehall II cohort participants screened in 2008 to 2009, and followed for 11.7 years (mean=10.3, SD=1.81), without history of stroke, myocardial infarction, or coronary heart disease. Mean age of the sample was 65.0 years (SD=5.6), 2831 participants (73.8%) were male and mean atherosclerotic cardiovascular disease risk score was 13.8%. At the end of follow-up, 411 individuals (10.7%) had suffered a major cardiovascular event. Those in the highest aortic pulse wave velocity quartile were at high risk (hazard ratio, 2.99 [95% CI, 2.25-3.97]) and reached the threshold for statin medication (7.5% risk) after 5 years whereas others reached it after 10 years (difference P<0.001). The addition of aortic pulse wave velocity to the risk score improved the C statistic (0.68 versus 0.67, P=0.03) and net reclassification index (4.6%, P=0.04 and 11.3%, P=0.02). Our results show that aortic stiffness predicted major adverse cardiovascular events in a cohort of elderly individuals, improving the performance of a widely used cardiovascular disease risk estimator. Aortic pulse wave velocity measurement is scalable, radiation-free, and easy to perform. Further studies on its applicability in cardiovascular disease risk assessment in primary care settings are needed.

Prevalence of parkinsonism and Parkinson disease in urban and rural populations from Latin America: A community based study

SummaryBackgroundAge and gender specific prevalence rates for parkinsonism and Parkinson's disease (PD) are important to guide research, clinical practice, and public health planning; however, prevalence estimates in Latin America (LatAm) are limited. We aimed to estimate the prevalence of parkinsonism and PD and examine related risk factors in a cohort of elderly individuals from Latin America (LatAm).MethodsData from 11,613 adults (65+ years) who participated in a baseline assessment of the 10/66 study and lived in six LatAm countries were analyzed to estimate parkinsonism and PD prevalence. Crude and age-adjusted prevalence were determined by sex and country. Diagnosis of PD was established using the UK Parkinson's Disease Society Brain Bank's clinical criteria.FindingsIn this cohort, the prevalence of parkinsonism was 8.0% (95% CI 7.6%–8.5%), and the prevalence of PD was 2.0% (95% CI 1.7%–2.3%). PD prevalence increased with age from 1.0 to 3.5 (65–69vs. 80 years or older, p < 0.001). Age-adjusted prevalence rates were lower for women than for men. No significant differences were found across countries, except for lower prevalence in urban areas of Peru. PD was positively associated with depression (adjusted prevalence ratio [aPR] 2.06, 95% CI 1.40–3.01, I2 = 56.0%), dementia (aPR 1.57, 95% CI 1.07- 2.32, I2 = 0.0%) and educational level (aPR 1.14, 95% CI 1.01– 1.29, I2 = 58.6%).InterpretationThe reported prevalence of PD in LatAm is similar to reports from high-income countries (HIC). A significant proportion of cases with PD did not have a previous diagnosis, nor did they seek any medical or neurological attention. These findings underscore the need to improve public health programs for populations currently undergoing rapid demographic aging and epidemiological transition.FundingThe funding source had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Out-of-hospital cardiac arrest in elderly individuals

Abstract Background Out-of-hospital cardiac arrest (OHCA) is associated with poor outcome, particularly in elderly people. Due to the shift in global demographics towards an ageing population, understanding risk factors for OHCA is essential for the development of primary prevention strategies. Thus, we aimed to identify predictors for OHCA in a large, community-dwelling cohort of elderly individuals. Methods We analyzed data from 11,156 participants enrolled in a randomized, placebo-controlled primary prevention trial, investigating the effect of low-dose aspirin in individuals aged 70 years or above. At baseline all participants had no prior cardiovascular disease events, dementia or major physical disability. OHCA events occurring within 5 years were identified by probabilistic data-linkage with a state-wide out-of-hospital cardiac arrest registry. Possible predictors included age, sex, anthropometric measures, conventional cardiovascular risk factors, renal function and frailty. To evaluate the association with OHCA, we performed univariable and multivariable Cox regression analyses. In exploratory analyses we also evaluated the effect of low-dose aspirin on OHCA events. Results In the cohort 54.7% were female and median age was 74.1 years (Interquartile Range [IQR] 71.8–77.7). During a median follow up time of 4.7 years (IQR 3.4–6.0) we recorded 67 OHCA events with presumed cardiac cause. The incidence rate was 1.07 per 1,000 person-years (95% Confidence-Interval [CI] 0.80–1.40). The mortality rate following OHCA was 91.2% (n=62). Univariable Cox regression analyses identified age, sex, weight, abdominal circumference, serum creatinine, diabetes, arterial hypertension, intake of antihypertensive medication and pre-frailty as predictors for the outcome. In multivariable Cox regression analyses we identified age (Hazard Ratio [HR] 1.06, CI 1.00–1.13), female sex (HR 0.49, CI 0.26–0.94) and pre-frailty (HR 1.92, CI 1.03–3.58) to be independent predictors (Table). In exploratory analyses there was no effect of low-dose aspirin on OHCA (HR 1.52, CI 0.87–2.70). Conclusion In a large, contemporary cohort of healthy, elderly individuals we describe a significant incidence of OHCA events associated with a very high mortality. We identified age, sex and pre-frailty, but interestingly not conventional cardiovascular risk factors as independent predictors of OHCA. We could not show a benefit of low-dose aspirin treatment, although the number of events was small. Our findings emphasize the importance of preventive strategies for pre-frailty in elderly individuals. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): The ASPREE study was primarily funded by the National Institute of Aging and National Cancer Institute at the National Institutes of Health (grant number U01AG029824), the Australian National Health &amp; Medical Research Council (grants 334047 &amp; 1127060), Monash University (Australia) and the Victorian Cancer Agency (Australia). Multivariable Cox regression analyses

Prevalence of Clonal Hematopoiesis and Mutation Patterns in Unexplained Anemia of Community-Dwelling Elderly Individuals: A Case-Control Study

The prevalence of anemia in the general population rises sharply after the age of 50, reaching 20% or more in individuals aged 85 years or older. In up to one third of cases, the origin of anemia remains unexplained, i.e. not attributable to causes detectable with conventional tests or to any concomitant diseases, and several potential mechanisms have been proposed, including myelodysplasia (MDS) (PMID 15238427). Recent studies showed that somatic mutations are commonly acquired in hematopoietic cells during aging, and are associated with increased risk of hematologic malignancies (PMID 25426837; 25426838). In a recent analysis in patients with unexplained cytopenia undergoing a comprehensive diagnostic workup, we found that mutation profiling was highly predictive of myeloid neoplasm (PMID 28424163).In this study, we performed a mutation analysis in a cohort of elderly individuals with unexplained anemia and in sex- and age-matched control subjects both selected from a population-based study, as well as in a matched group of patients with MDS, with the aim to investigate the relationship between clonal hematopoiesis, mutation profile and unexplained anemia in community-dwelling elderly subjects.Seventy individuals aged 60 years or older having anemia according to WHO criteria, not explained by nutritional deficiency, renal failure or inflammation, and 105 sex- and age-matched control subjects (ratio 1:1.5) were selected from the “Val Borbera” Study, a population-based study recruiting a total of 1803 people. In addition, 105 matched control patients with newly diagnosed MDS without excess blasts was analyzed. Median age was 78 years (range 62-102), 133 individuals were males, 147 females. A panel of 54 genes was analyzed on peripheral blood cells, using a HiSeq 2500 platform (Illumina, San Diego, CA) (median depth 1550, range 845-2057).Among community-dwelling individuals, a significant effect of age was observed on mutation prevalence (P=.023); however, this effect was limited to controls. A significantly higher mutation rate was observed in cases compared with controls (42.9% vs 24.8%, P=.014). This rate was even higher when restricting the analysis to individuals with hemoglobin <12.5 g/dL in males and <11.5 g/dL in females and/or MCV>105 fL (63% vs 24.8%, P<.001). A significantly higher Variant Allele Frequency (VAF) was found in cases compared with controls (median value 0.21, range 0.02-0.51 vs 0.07, 0.02-0.38; P=.035). A significantly higher number of individuals with two somatic mutations was found among cases compared with non-anemic controls (14.3% vs 1.9%, P=.003). Subjects with two somatic mutations showed a significantly higher VAF compared with those having an isolated mutation (median value 0.31, range 0.03-0.50 vs 0.06, 0.06-0.51; P=.008). In a multivariable regression analysis, number of mutations per subject and VAF were independent predictors of anemia (OR=7.55, P=.03, and OR=1.67, P=.037, respectively). A significantly higher prevalence of splicing factor mutations was found in cases compared with controls (11.1% vs 0%, P=.008). In most individuals with multiple mutated genes, mutation pattern included a DNA methylation gene mutation associated with a subclonal mutation.When comparing community dwelling individuals with unexplained anemia with a matched group of patients with MDS, a significantly higher number of subjects with two or more mutations was found in MDS compared with unexplained anemia (47.6% vs 14.3%, P<.001). MDS patients showed a significantly higher VAF compared with individuals with unexplained anemia (median value 0.41, range 0.02-0.93 vs 0.21, 0.02-0.51; P<.001). Finally, a significantly higher prevalence of splicing factor mutations was observed in MDS compared with unexplained anemia (55.2% vs 11.1%, P<.001).In conclusion, this study provides evidence of a high rate of clonal hematopoiesis in community-dwelling elderly individuals with unexplained anemia compared with matched controls with normal hemoglobin values, mainly sustained by an enrichment in subjects with accumulation of mutations proven highly predictive of myeloid neoplasm with myelodysplasia. Mutation analysis on peripheral blood cells may complement current diagnostic approach to unexplained anemia in the frail population of elderly individuals, increasing compliance to diagnostic tests and overall the diagnostic accuracy of myeloid neoplasms. DisclosuresRizzo:enGenome srl: Employment. Camaschella:Vifor Pharma: Membership on an entity's Board of Directors or advisory committees.

The relation between illness perception profiles and self management strategies in a cohort of elderly individuals with knee pain a cross-sectional study based on the Frederiksberg cohort

Purpose: Knee pain among the elderly has been shown to be an early sign of later incident radiographic knee OA and affects the daily life of the individual while it incurs high costs on society. Therefore, early preventive measures against pre-OA knee pain are important. Many individuals with pre-OA knee pain self-manage their condition without seeking health care assistance until a further deterioration of the conditions has occurred. Conceptually, perception of illness is a determinant of how an individual chose to self-manage and seek assistance in conditions like heart disease, sleep disorders, and inflammatory arthritis.

Prevalence of Parkinsonism and Parkinson Disease in Urban and Rural Populations from Latin America: A Community Population-Based Survey

Background: Age-gender-specific prevalence rates for parkinsonism and Parkinson’s disease (PD) are important to guide research, clinical practice and public health planning; however, prevalence estimates in Latin America (LatAm) are limited. We aimed to estimate the prevalence of parkinsonism and PD and examine its risk factors in a cohort of elderly individuals from LatAm. Methods: Data from 11,613 adults (65+ years) who participated in a baseline assessment of the 10/66 study and who lived in six LatAm countries were analyzed to estimate Parkinsonism and PD prevalence. Crude and age-adjusted prevalence were determined by sex and country. Diagnosis of PD was established using the UK Parkinson’s Disease Society Brain Bank’s clinical criteria. Findings: In this cohort, the prevalence of Parkinsonism was 8.0% (95% CI 7.6%-8.5%), and the prevalence of PD was 2.0% (95% CI 1.7%-2.3%). PD prevalence increased with age from 1.0 to 3.5 (65-69 vs. 80 years or older, p<0.001). Age-adjusted prevalence rates were lower for women than for men. No significant differences were found across countries, except for lower prevalence in urban areas of Peru. PD was positively associated with depression (adjusted prevalence ratio [aPR] 2.06, 95% CI 1.40-3.01, I2=56.0%), dementia (aPR 1.57, 95% CI 1.07- 2.32, I2=0.0%) and educational level (aPR 1.14, 95% CI 1.01- 1.29, I2=58.6%). Interpretation: The reported prevalence of PD in LatAm is similar to the prevalence in HIC. A significant proportion of cases with PD did not have a previous diagnosis, nor did they seek any medical or neurological attention. These findings underscore the need to improve public health programs for populations that are currently undergoing rapid demographic aging and epidemiological transition. Funding: The 10/66 Dementia Research Group’s research has been funded by the Wellcome Trust Health Consequences of Population Change Program (GR066133 – Prevalence phase in Cuba and Brazil; GR080002- Incidence phase in Peru, Mexico, Argentina, Cuba, Dominican Republic, Venezuela, and China). Declaration of Interest: None to declare. Ethical Approval: This project was approved by local institutional review boards and the King’s College London Research Ethics Committee.

Is statin related to conversion of mild cognitive impairment to dementia?

AbstractBackgroundAlthough randomized controlled trials have not confirmed cognitive impairing effects of statins, continuing evidence suggests statins have the ability to cause reversible cognitive impairment in some patients. Paradoxically, statins have also been shown to decrease risk of dementia, Alzheimer’s disease, and to improve cognitive impairment in some cases. However, randomized controlled trials have similarly failed to find the beneficial effect. We conducted evaluate the effect of statin on the conversion of mild cognitive impairment (MCI) to dementia in a Cohort of elderly individuals without functional and cognitive impaiment (NC) and with MCI patients.MethodCohort was reassessed annually by geriatricians and neuropsychologists for an average period of 3.01 ± 1.43 years. The effect of statin on cognition was evaluated when it was in use throughout the follow‐up period and, it was in use at any time during the follow‐up. Chi‐square and Fisher tests (categorical variables) and student t tests, ANOVA, Mann Whiney (continuous variables) were used.Results176 individuals were selected (53 CG, 111 with amnestic MCI ‐ aMCI‐ and 12 with non‐amnestic MCI ‐naMCI), aged 76.52 ± 7.27 years, 69% female and 3.61 ± 3.23 years of schooling. We observed conversion of aMCI to dementia in 27 participants (92.6% Alzheimer dementia), corresponding to a conversion rate of 24.3%. In the aMCI group, the remission rate was 13.5%. 51.1% of the sample received statin at some point during the follow‐up and 30.7% used it throughout the study. 98.8% of prescribed statins had moderate potency. Comparing stable MCI group throughout the study with the group which progressed to dementia, the group that used it any time during the follow‐up analysis showed a p‐value of 0.104, whereas the group that used it during the entire follow‐up showed a p‐value of 0.166. Comparing remission and conversion groups, the one that used statin any time during the follow‐up showed a p‐value of 0.542, patients who received statin during the entire follow‐up had a p‐value of 0.746.ConclusionStatins were not associated with conversion from aMCI to dementia, even when used throughout the entire follow‐up.

Association of brain network dynamics with plasma biomarkers in subjective memory complainers

Using a single integrated analysis, we examined the relationship between brain networks and molecular pathways in a cohort of elderly individuals at risk for Alzheimer's disease. In 205 subjective memory complainers (124 females, mean age: 75.7 ± 3.4), individual functional connectome was computed for a total of 3081 functional connections (set A) and 6 core plasma biomarkers of Alzheimer's disease (set B) were assessed. Partial least squares correlation analysis identified one dimension of population covariation between the 2 sets (p < 0.006), which we named bioneural mode. Five core plasma biomarkers and 190 functional connections presented bootstrap ratios greater than the critical value |1.96|. T-tau protein showed a trend toward significance (bootstrap resampling = 1.64). The salience, the language, the visuospatial, and the default mode networks were the strongest significant networks. We detected a strong association between network dynamics and core pathophysiological blood biomarkers. Innovative composite biomarkers, such as the bioneural mode, are promising to provide outcomes and better inform drug development and clinical practice for neurodegenerative diseases.

P4496Copeptin and coronary artery calcium score in elderly adults without a cardiovascular history. A report from the ICELAND MI cohort

Abstract Background Copeptin, a marker for vasopressin, is related to advanced cardiovascular disease such as myocardial infarction. Purpose The aim of the present investigation was to assess whether copeptin is associated with the different atherosclerotic plaque stages expressed by coronary artery calcium scores (CAC score). Methods Copeptin and CAC score were studied in 677 participants in the ICELANDIC MI cohort without a history of a myocardial infarction at baseline. The Agatston method was used to measure coronary artery calcification visualized by means of computed tomographic scans. The CAC score was categorized into four classes: 0, 1–99, 100–399, and ≥400. Correlations between the CAC score and copeptin were assessed using Spearman's Rank Correlation while the predictive value of copeptin and CAC score were evaluated with Cox proportional Hazard regression analysis (unadjusted and adjusted for age groups, serum creatinine, gender, hypertension and type 2 diabetes mellitus). The primary outcome was cardiovascular events (CVE) while total mortality served as secondary outcome. Results The median copeptin level was 6.4 pmol/L and the median CAC score 227.0 (IQR: 48.3–692.4) for the total cohort. The highest copeptin level was seen in people with a CAC score ≥400. Copeptin predicted total mortality in the unadjusted analysis and the CAC score predicted both outcomes. Only the CAC score that predicted outcome following adjustments (CVE: HR 1.35, 95% CI 1.23–1.48; p&lt;0.001; and total mortality: HR 1.29, 95% CI 1.16–1.43; p&lt;0.001). The cardiovascular prognosis was similar in those with CAC score less than 400 and above 400 regardless of the copeptin level (Figure). Figure 1 Conclusion In this cohort of elderly individuals without a previous MI a high CAC score was as a significant predictor of future cardiovascular events. People with high a CAC score had elevated copeptin levels but copeptin did not serve as a prognostic indicator. This suggests that copeptin elevation in people with CAD is an expression for the general state of disease rather than an indicator of a pathophysiological role of vasopressin in this context.

Visual impairment in aging and cognitive decline: experience in a Memory Clinic

Visual impairment is common in people living with dementia and regular ophthalmological exams may improve their quality of life. We evaluated visual function in a cohort of elderly individuals and analyzed its association with their degree of cognitive impairment. Participants underwent neurological and neuropsychological exams, neuro-ophthalmological assessment (visual acuity, intraocular pressure, rates of past ophthalmological pathologies, use of ocular correction, treatments and surgeries) and optical coherence tomography (OCT) scan. We analyzed differences in ophthalmological characteristics among diagnostic groups. The final sample of 1746 study participants aged ≥ 50 comprised 229 individuals with Subjective Cognitive Decline (SCD), 695 with mild cognitive impairment (MCI) and 833 with Dementia (Alzheimer disease: n = 660; vascular dementia: n = 92, Lewy body dementia: n = 34; frontotemporal dementia: n = 19 and other: n = 28). Age, gender and education were used as covariates. Patients with Dementia, compared to those with SCD and MCI, presented worse visual acuity (p < 0.001), used less visual correction (p = 0.02 and p < 0.001, respectively) and fewer ophthalmological treatments (p = 0.004 and p < 0.001, respectively) and underwent fewer ocular surgeries (p = 0.009 and p < 0.001, respectively). OCT image quality worsened in parallel to cognitive decline (Dementia vs SCD: p = 0.008; Dementia vs MCI: p < 0.001). No group differences in past ophthalmological disorders or abnormal OCT findings were detected. Efforts should be made to ensure dementia patients undergo regular ophthalmological assessments to correct their visual function in order to improve their quality of life.

Association of Cognition and Age-Related Hearing Impairment in the English Longitudinal Study of Ageing

Evidence has linked age-related hearing impairment (ARHI) with cognitive decline; however, very few studies (none in the United Kingdom) explore this link in large well-characterized groups of community-dwelling individuals. To investigate the link between ARHI and cognitive decline using a cohort of elderly individuals from the United Kingdom and explore untreated hearing loss and social isolation as potential explanations for the observed link. This cross-sectional analysis of wave 7 (June 2014 through May 2015) of the English Longitudinal Study of Ageing (ELSA) sampled men and women 50 years or older and living in the United Kingdom in a community setting. Those with a diagnosis of dementia, Alzheimer disease, or Parkinson disease or with ear infections and cochlear implants were excluded. Data were analyzed from August 1, 2017, through May 25, 2018. Memory and executive function as measures of cognitive function and hearing acuity derived from the HearCheck screener device (Siemens). Of a cohort of 9666 members in wave 7 of ELSA, 7385 were eligible for analysis after applying exclusion criteria (55.1% women; mean [SD] age, 67.4 [9.4] years). Of these, 3056 (41.4%) had mild hearing loss and 755 (10.2%) had severe hearing loss; 834 (11.3%) used a hearing aid; and 7155 (96.9%) were white. Hearing loss had a negative association with cognition; for those with moderate to severe loss, the score on memory assessment was a full 1 point less (-1.00; 95% CI, -1.24 to -0.76), ceteris paribus, relative to those with no hearing loss. However, this association was seen only in the individuals with untreated hearing loss (ie, those who did not use hearing aids) (-1.16; 95% CI, -1.45 to -0.87). Evidence suggests that social isolation acts as a mediating factor. Although hearing loss and cognition are linked, untreated hearing loss drives the association. Social isolation is a mediating factor in the link for those who have untreated hearing loss. Cognitive decline associated with ARHI is probably preventable by early rehabilitation and increased opportunistic screening for the elderly.

Association of Excessive Daytime Sleepiness With Longitudinal β-Amyloid Accumulation in Elderly Persons Without Dementia

Aging is associated with excessive daytime sleepiness (EDS), which has been linked to cognitive decline in the elderly. However, whether EDS is associated with the pathologic processes of Alzheimer disease remains unclear. To investigate whether EDS at baseline is associated with a longitudinal increase in regional β-amyloid (Aβ) accumulation in a cohort of elderly individuals without dementia. This prospective analysis included participants enrolled in the Mayo Clinic Study of Aging, a longitudinal population-based study in Olmsted County, Minnesota. Of 2900 participants, 2172 (74.9%) agreed to undergo carbon 11-labeled Pittsburgh compound B positron emission tomography (PiB-PET). We included 283 participants 70 years or older without dementia who completed surveys assessing sleepiness at baseline and had at least 2 consecutive PiB-PET scans from January 1, 2009, through July 31, 2016, after excluding 45 (13.7%) who had a comorbid neurologic disorder. Excessive daytime sleepiness was defined as an Epworth Sleepiness Scale score of at least 10. The difference in Aβ levels between the 2 consecutive scans (ΔPiB) in Aβ-susceptible regions (prefrontal, anterior cingulate, posterior cingulate-precuneus, and parietal) was determined. Multiple linear regression models were fit to explore associations between baseline EDS and ΔPiB while adjusting for baseline age, sex, presence of the apolipoprotein E ε4 allele, educational level, baseline PiB uptake, global PiB positivity (standardized uptake value ratio ≥1.4), physical activity, cardiovascular comorbidities (obesity, hypertension, hyperlipidemia, and diabetes), reduced sleep duration, respiratory symptoms during sleep, depression, and interval between scans. Of the initial 283 participants, mean (SD) age was 77.1 (4.8) years; 204 (72.1%) were men and 79 (27.9%) were women. Sixty-three participants (22.3%) had EDS. Baseline EDS was significantly associated with increased regional Aβ accumulation in the anterior cingulate (B coefficient = 0.031; 95% CI, 0.001-0.061; P = .04), posterior cingulate-precuneus (B coefficient = 0.038; 95% CI, 0.006-0.069; P = .02), and parietal (B coefficient = 0.033; 95% CI, 0.001-0.065; P = .04) regions. Association of EDS with longitudinal Aβ accumulation was stronger in participants with baseline global PiB positivity in the anterior cingulate (B coefficient = 0.065; 95% CI, 0.010-0.118; P = .02) and cingulate-precuneus (B coefficient = 0.068; 95% CI, 0.009-0.126; P = .02) regions. Baseline EDS was associated with increased longitudinal Aβ accumulation in elderly persons without dementia, suggesting that those with EDS may be more vulnerable to pathologic changes associated with Alzheimer disease. Further work is needed to elucidate whether EDS is a clinical marker of greater sleep instability, synaptic or network overload, or neurodegeneration of wakefulness-promoting centers. Early identification of patients with EDS and treatment of underlying sleep disorders could reduce Aβ accumulation in this vulnerable group.

Evaluation of amyloid status in a cohort of elderly individuals with memory complaints: validation of the method of quantification and determination of positivity thresholds.

Our aim is to validate the process steps implemented by the French CATI platform to assess amyloid status, obtained from 18F-Florbetapir PET scans, in a cohort of 318 cognitively normal subjects participating in the INSIGHT-preAD study. Our objective was to develop a method with partial volume effect correction (PVEC) on untransformed PET images, using an automated pipeline ("RACHEL") adapted to large series of patients and including quality checks of results. We compared RACHEL using different options (with and without PVEC, different sets of regions of interest), to two other methods validated in the literature, referred as the "AVID" and "CAEN" methods. A standard uptake value ratio (SUVR) was obtained with the different methods for participants to another French study, IMAP, including 26 normal elderly controls (NEC), 11 patients with mild cognitive impairment (MCI) and 16 patients with Alzheimer's disease (AD). We determined two cutoffs for RACHEL method by linear correlation with the other methods and applied them to the INSIGHT-preAD subjects. RACHEL including PVEC and a combination of the whole cerebellum and the pons as a reference region allowed the best discrimination between NEC and AD participants. A strong linear correlation was found between RACHEL and the other two methods and yielded the two cutoffs of 0.79 and 0.88. According to the more conservative threshold, 19.8% of the INSIGHT-preAD subjects would be considered amyloid positive, and 27.7% according to the more liberal threshold. With our method, we clearly discriminated between NEC with negative amyloid status and patients with clinical AD. Using a linear correlation with other validated cutoffs, we could infer our own positivity thresholds and apply them to an independent population. This method might be useful to the community, especially when the optimal cutoff could not be obtained from a population of healthy young adults or from correlation with post-mortem results.

Orthostatic Hypotension and Risk of Incident Dementia: Results From a 12-Year Follow-Up of the Three-City Study Cohort.

Several studies indicate a potential link between orthostatic hypotension (OH) and incident dementia but without substantial evidence to date. Our objective is to study the association between OH and dementia in a cohort of elderly individuals. To do so, baseline lying and standing blood pressure measurements were taken from 7425 subjects in the Three-City study. These subjects were then followed-up for 12 years. Cox proportional hazard models, adjusted for potential confounders, were used to estimate the risk of incident dementia according to OH status. Sensitivity analysis was performed using the so-called illness-death model, a specific statistical method which takes into account competitive risk with death. OH frequency was found to be around 13%, and 760 cases of dementia were diagnosed during follow-up. We observed significant associations between the presence of OH at baseline and the occurrence of dementia during the follow-up, with an increased risk of at least 25% observed regardless of the OH threshold and the statistical method used. In conclusion, there is an association between OH and dementia. Considering that OH is a common condition and is easy to measure, OH measurements could help to identify subjects with higher risk of dementia. Moreover, reducing OH could be a step to prevent conversion to dementia.

A populational-based survey on the prevalence, incidence, and risk factors of urinary incontinence in older adults-results from the "SABE STUDY".

To estimate the prevalence and incidence of urinary incontinence (UI) and identify the associated risk factors in a cohort of elderly individuals in Brazil. In 2006, individuals aged ≥60 years were selected from the SABE Study (Health, Well-being, and Aging). The dependent variable was reported UI in 2009. UI was assessed using the International Consultation on Incontinence Questionnaire Urinary Incontinence-Short Form (ICIQ-UI SF). Incidence was measured in units of 1000 person-years, and Cox regression was applied for data analysis. Multivariate analysis was used to assess risk factors for UI. Incidence risk ratio (IRR) was used for comparison. This is the first study to examine the incidence of UI in Brazilian elderly individuals. In total, 1413 individuals were included; the mean age was 74.5 years, and 864 (61.8%) participants were female. The risk of UI was greater among women with cancer (other than skin) and among those with diabetes. In men, the risk of UI was greater for those in Instrumental Activities of Daily Living (IADL) category "5-8" and those who self-reported a "fair" health status. The prevalence of UI was 14.2% and 28.2% for men and women, respectively. The incidence rate of UI was 25.6 and 39.3 (×1000 person-years) for men and women, respectively. The incidence rate of UI among older adults in the Brazilian community was high for elderly individuals. The identified risk factors were diabetes and IADL category 5-8 (women) as well as cancer (other than skin) and self-reported health status (male).

Determinants of Receipt of Stem Cell Transplant in Elderly Medicare Beneficiaries with Multiple Myeloma

Introduction: Multiple myeloma (MM) is a disease of the elderly with a median age at diagnosis of 70 years. Autologous stem cell transplantation (ASCT) is a preferred treatment for younger patients but is also an option for older adults (i.e., patients >65 years) with good performance status. A previous SEER-Medicare study of MM patients diagnosed from 2000-2007 found that 5.8% underwent ASCT (Winn, et al. JNCI, 2015). The availability of ASCTs for older adults with MM has increased in the past decade due to improvement in supportive care and Medicare coverage approval. Apart from age and medical eligibility, several patient and contextual factors, such as comorbidity, may influence the receipt of ASCT in the MM population. There is limited information on the determinants of receipt of ASCT in older adults over the past decade in the US.Objective: To identify ASCT recipients among a cohort of elderly individuals with MM in order to determine characteristics associated with receiving ASCT. Specifically, this study identifies patient and contextual factors associated with the receipt of ASCT.Methods: This retrospective cohort study used Surveillance, Epidemiology, and End Results (SEER) registry and linked Medicare claims (SEER-Medicare) data. We identified individuals aged 66 and above, with an incident diagnosis of MM between 2007 and 2011 as well as claims data from 2006 to 2012. We required continuous enrollment in Medicare Parts A and B 12 months prior to and including the month of diagnosis and six months post-diagnosis. We required continuous Part D enrollment two months pre- and six months post-diagnosis. Patients were followed until death or censoring due to non-continuous Parts A and B enrollment after six months. ICD-9 and HCPCS codes were used to identify ASCT. Charlson Comorbidity Index (CCI) was used to measure the number of comorbid conditions at the time of MM diagnosis using claims one year prior to diagnosis. Student's t-test and Chi-square test of proportions were used to compare those who received ASCT to those who did not based on patient-level factors (i.e., age, gender, race, comorbidity status), geographic regions (i.e., Northeast, Midwest, West and South), and over time (diagnosed in 2007-2009 vs. diagnosed in 2010 to 2011). We also measured the time to ASCT for those who underwent ASCT.Results: Among 3,318 individuals with MM who met our inclusion criteria, 226 (6.8%) underwent ASCT during the follow-up period. ASCT recipients were younger, more likely to be male, white non-Hispanic, and have fewer comorbid conditions (Table 1). The median time from MM diagnosis to ASCT was 278 days. The rate of ASCT among recipients aged 66-69 was 23.2%, 7.3% among recipients aged 70-74, and 0.84% among those aged 75+ (p<0.001). The rate of ASCT was higher among males (8.5%) than females (5.2%) (p<0.001). Rates of ASCT were higher among those who were non-Hispanic white (8.1%), compared to those who were non-Hispanic black (3.5%) or of another race/ethnicity (4.1%) (p<0.001). Among those with CCI=0, 9.9% underwent ASCT, while 7.2% of those with CCI=1 underwent ASCT and 2.7% of those with CCI>1 underwent ASCT (p<0.001). Rates of ASCT were similar across the geographic regions (p=0.15). Of those who were diagnosed in 2007-2009, 6.0% received transplant, while 7.8% of those who were diagnosed in 2010-2011 received transplant (p=0.04).Conclusion: ASCT is performed in less than 1 in 10 patients aged 66 and older. A greater proportion of ASCT recipients were non-Hispanic white, male, diagnosed at a younger age, and had a lower comorbidity burden compared to non-transplant patients. Comparing the pre-2007 estimate from the aforementioned study to our early (2007-09) and late (2010-11) period estimates, our results illustrate an upward trend in ASCT over the past decade. We were unable to identify smoldering MM patients who would not be candidates for ASCT. This may bias our estimates downward. The aforementioned previous study found that 62% of recipients were 66-69, 32% of recipients were 70-74, while 6% were 75+ (Winn, et al. JNCI, 2015). These rates did not differ greatly from our findings indicating that the age distribution of ASCT recipients has remained stable over a 10 year period of observation. Future studies should investigate the implications of these differences for post-transplant outcomes among older MM patients. [Display omitted] DisclosuresGoto:Novartis AG: Research Funding. Onukwugha:Takeda: Research Funding; IMPAQ International: Honoraria; Bayer Healthcare: Research Funding. Seal:Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment, Equity Ownership. Romanus:Takeda: Employment. Yong:Takeda: Employment. Slejko:Takeda: Research Funding; PhRMA: Research Funding; National Pharmaceutical Council: Research Funding.

What physical performance measures predict incident cognitive decline among intact older adults? A 4.4 year follow up study

Reductions in physical performance, cognitive impairment (CI) and decline (CD), are common in older age, but few prospective cohort studies have considered the relationship between these domains. In this study we investigated whether reduced physical performance and low handgrip/lower limbs strength, could predict a higher incidence of CI/CD during a 4-year follow-up among a cohort of elderly individuals. From 3099 older community-dwelling individuals initially enrolled in the Progetto Veneto Anziani (PRO.V.A.) study, 1249 participants without CI at the baseline were included (mean age 72.2years, 59.5% females). Physical performance measures included the Short Physical Performance Battery (SPPB), 4m gait speed, chair stands time, leg extension and flexion, handgrip strength, and 6-Minute Walking Test (6MWT), categorized in gender-specific tertiles. CI was defined as a Mini-Mental State Examination (MMSE) score below 24; CD a decline of 3 or more points in the MMSE without CI. At baseline, participants developing CI during follow-up scored significantly worse across all physical performance measures compared to those that retained normal cognitive status. After adjusting for potential confounders, a significant trend for MMSE changes was noted for all physical performance tests, except for the SPPB and chair stands time. Multinomial logistic regression revealed that slow gait speed at baseline significantly predicted CD at follow up. Poor SPPB performance and slower gait speed predicted the onset of CI at the follow-up. In conclusion, slow walking speed appears to be the best independent predictor of poor cognitive status over a 4.4-year follow-up, while other items of SPPB were also significantly associated with CI.

Excessive daytime sleepiness and antipathogen drug consumption in the elderly: a test of the immune theory of sleep.

The evolutionary reasons for sleep remain controversial. The immune theory of sleep suggests that sleep is essential to the immune system, allowing organisms to allocate more energy to their immunity. This hypothesis was tested by exploring the links between excessive daytime sleepiness (EDS) and vulnerability to infectious diseases in a large (n = 9294) cohort of elderly individuals, with information on socio-demographics, daily habits, and medical characteristics. At the two-year and four-year follow-ups, we obtained individual data from the national healthcare insurance about all medications prescribed to the participants between 2001 and 2003 (n = 2865). We found an independent positive association between EDS and the consumption of some anti-pathogen drugs. This relationship was mostly explained by fungal and parasitic infections rather than by viral and bacterial ones. These results, although based on correlations, are consistent with the idea that EDS as a proxy of altered sleep quality/quantity may affect the efficiency of the immune system, and hence vulnerability to infections.

Characterising neural signatures of successful aging: Electrophysiological correlates of preserved episodic memory in older age

While aging is associated with a gradual decline in memory, substantial preservation of function is observed in certain individuals and dissecting this heterogeneity is paramount to understanding successful aging. A cohort of elderly individuals were classified according to their level of memory preservation and administered a test of episodic memory in which participants were cued to learn or simply read each word and then to identify previously presented items in a delayed recognition phase. Mathematical modelling revealed that relatively preserved memory function was specifically linked to a faster rate of memorial evidence accumulation (drift rate). Analysis of event-related potentials at encoding revealed that high-performing elderly exhibited signals over parietal regions that discriminated between words to be learned vs. read for an additional 300-ms compared to young subjects suggesting a compensatory encoding mechanism that was absent in the low-performing group. At recognition, parietal signals associated with recollection processes discriminated previously learned words from read words in the young and high-performing old but not in low-performing old. These results reveal that successful aging is associated with specific adaptive neural markers during both encoding and retrieval.