Meta-Analysis of Prevalence and Risk Factors for Cognitive Decline and Improvement After Transcatheter Aortic Valve Implantation

Changes to cognition, both decline and improvement, are commonly reported after transcatheter aortic valve implantation (TAVI). However, previous systematic reviews and meta-analyses have missed these subgroups by assessing whole-group-averages for cognitive outcomes. We sought to pool estimates to identify the prevalence of cognitive decline and improvement after TAVI, as well as associated factors for these outcomes. A systematic review identified 15 articles appropriate for meta-analysis. When robust cognitive change definitions were employed, the pooled prevalence of incident cognitive impairment up to 1-, 1 to 6-, and ≥6-months post-TAVI was 7%, 14%, and 12%, respectively. For cognitive improvement, the prevalence from 1 to 6 months and ≥6 months after TAVI was estimated to be 19% and 11%, respectively. Two factors were associated with these cognitive outcomes: (1) using a cerebral embolic protection device was associated with decreased prevalence of cognitive decline up to 1-week post-TAVI; (2) baseline cognitive impairment had a large association with post-TAVI cognitive improvement. In conclusion, cognitive decline and cognitive improvement are experienced by approximately 7% to 19% of patients after TAVI, respectively. Those with the lowest cognitive performance pre-TAVI appear to have the most to gain in terms of cognitive improvement post-TAVI. Identifying further predictive factors for cognitive decline and improvement post-TAVI will facilitate a personalized-medicine approach for cognitive care and prognosis

Identifying New Factors Associated With Cognitive Decline and Delirium After Transcatheter Aortic Valve Implantation: A Study Protocol

Background: Transcatheter aortic valve implantation (TAVI) has become the standard-of-care for treatment of severe symptomatic aortic stenosis and is also being increasingly recommended for low-risk patients. While TAVI boasts positive post-procedural outcomes, it is also associated with cognitive complications, namely delirium and cognitive decline. There is a pressing need for accurate risk tools which can identify TAVI patients at risk of delirium and cognitive decline, as risk scores designed for general cardiovascular surgery fall short. The present effect-finding exploratory study will assess the utility of various measures in the context of aging and frailty in predicting who will and who will not develop delirium or cognitive impairment following TAVI. The measures we propose include gait, visual symptoms, voice, swallowing, mood and sleep. Methods: This is an observational prospective cohort study focused on identifying pre-procedural risk factors for the development of delirium and cognitive decline following TAVI. Potential risk factors will be measured prior to TAVI. Primary outcomes will be post-procedure cognitive decline and delirium. Secondary outcomes include activities of daily living, quality of life, and mortality. Delirium presence will be measured on each of the first 2 days following TAVI. All other outcomes will be assessed at 3-, 6-, and 12-months post-operatively. A series of logistic regressions will be run to investigate the relationship between potential predictors and outcomes (presence vs. absence of either delirium or cognitive decline). Discussion: This study will assess the strengths of associations between a range of measures drawn from frailty and aging literature in terms of association with cognitive decline and delirium following TAVI. Identified measures can be used in future development of TAVI risk prediction models, which are essential for the accurate identification of cognitive at-risk patients and successful application of pre-procedural interventions. Clinical Trial Registration: This trial is registered with the Australian New Zealand Clinical Trials Registry. [https://bit.ly/2PAotP5], [ACTRN12618001114235]

Meta-analysis of Prevalence and Risk Factors for Delirium After Transcatheter Aortic Valve Implantation

Delirium is a severe and common complication following transcatheter aortic valve implantation (TAVI). We sought to identify the prevalence and risk factors associated with the development of postprocedural delirium in patients aged over 60 years who underwent elective TAVI for aortic stenosis. Overall, 1,051 articles were searched, from which 9 studies were included. The prevalence of delirium following TAVI was higher in studies that assessed delirium for a minimum of 3 consecutive days (24.9%) compared with the studies that did not (2%). There were large effect sizes (d > 0.8) for 3 risk factors: acute kidney injury (odds ratio [OR] 5, p < 0.001), transapical approach (OR 4, p < 0.001) and carotid artery disease (OR 4, p < 0.001), whilst small effect sizes were found for a history of atrial fibrillation, prior stroke/transient ischemic attack, peripheral artery disease, hypertension, and prior cognitive impairment. In conclusion, 23% of patients 60 years and over who underwent TAVI experience delirium, a preventative cause of cognitive impairment and dementia. Recognition of risk factors for delirium after TAVI, such as a history of carotid artery disease, development of acute kidney injury, or use of a transapical approach, provides an opportunity to implement proven delirium preventative measures

Cognitive outcomes following coronary artery bypass grafting: A systematic review and meta-analysis of 91,829 patients

BACKGROUND: Cognitive impairments, including delirium, are common after coronary artery bypass grafting (CABG) surgery, as described in over three decades of research. Our aim was to pool estimates across the literature for the first-time, relative to time (from pre- to post-CABG) and diagnosis (cognitive impairment, delirium and dementia). METHODS: A systematic search of four databases was undertaken. 215 studies incorporating data from 91,829 patients were used to estimate the prevalence of cognitive impairments pre- and post-CABG, including delirium and dementia post-CABG, using random effects meta-analyses. RESULTS: Pre-surgical cognitive impairment was seen in 19% of patients. Post-operatively, cognitive impairment was seen in around 43% of patients acutely; this resolved to 19% at 4-6 months and then increased to 25% of patients between 6-months to 1-year post-operatively. In the long term, between 1 and 5-years post-operatively, cognitive impairment increased and was seen in nearly 40% of patients. Post-operative delirium was apparent in 18% of CABG patients which increased to 24% when a diagnostic instrument was utilized alongside clinical criteria. Dementia was present in 7% of patients 5-7 years post-surgery. CONCLUSION: The results of this meta-analysis demonstrate that cognitive impairment and delirium are major issues in CABG patients which require specific attention. It is imperative that appropriate methods for investigating cognitive impairment, and screening for delirium using a diagnostic instrument, occur in both pre-and post-CABG settings

APOE and ACE polymorphisms and dementia risk in the older population over prolonged follow-up: 10 years of incidence in the MRC CFA Study.

BACKGROUND: dementia risk conferred by apolipoprotein-E (APOE) and angiotensin-1-converting enzyme (ACE) polymorphisms have been reported for the MRC Cognitive Function and Ageing Study (CFAS) at 6-year follow-up. We concentrate on incident dementia risk over 10 years. METHODS: participants come from MRC CFAS, a multi-centre longitudinal population-based study of ageing in England and Wales. Three follow-up waves of data collection were used: 2, 6 and 10 years. Logistic regressions were undertaken to investigate associations between APOE (n = 955) and ACE (n = 856) alleles/genotypes and incident dementia. Two types of control groups were used: non-demented and highly functioning non-demented. Results were back-weighted. RESULTS: compared to APOE epsilon3, epsilon2 conferred protection of odds ratio (OR) = 0.3 (95% confidence interval, CI = 0.1-0.6) and epsilon4 risk of OR = 2.9 (95% CI = 1.7-4.9) for incident dementia. Compared to epsilon3/epsilon3, the epsilon3/epsilon4 and epsilon4/epsilon4 genotypes conferred risks of OR = 3.6 (95% CI = 1.8-7.3) and OR = 7.9 (95% CI = 1.6-39.2), respectively. The epsilon3/epsilon2 genotype protected against dementia (OR = 0.2, 95% CI = 0.1-0.7), and epsilon2/epsilon2 had a similar protective effect but with wide CIs (OR = 0.3, 95% CI = 0.1-1.7). Restricting the control group accentuated these differentials. The effects of ACE alleles/genotypes on incident dementia risk were small. CONCLUSIONS: APOE but not ACE is associated with late-onset incident dementia in the population. Using longer term follow-up with proper adjustment for attrition and incident cases increases estimates of risk

Association of Delirium With Cognitive Decline in Late Life: A Neuropathologic Study of 3 Population-Based Cohort Studies

Importance: Delirium is associated with accelerated cognitive decline. The pathologic substrates of this association are not yet known, that is, whether they are the same as those associated with dementia, are independent, or are interrelated. Objective: To examine whether the accelerated cognitive decline observed after delirium is independent of the pathologic processes of classic dementia. Design, Setting, and Participants: Harmonized data from 987 individual brain donors from 3 observational cohort studies with population-based sampling (Vantaa 85+, Cambridge City Over-75s Cohort, Cognitive Function and Ageing Study) performed from January 1, 1985, through December 31, 2011, with a median follow-up of 5.2 years until death, were used in this study. Neuropathologic assessments were performed with investigators masked to clinical data. Data analysis was performed from January 1, 2012, through December 31, 2013. Clinical characteristics of brain donors were not different from the rest of the cohort. Outcome ascertainment was complete given that the participants were brain donors. Exposures: Delirium (never vs ever) and pathologic burden of neurofibrillary tangles, amyloid plaques, vascular lesions, and Lewy bodies. Effects modeled using random-effects linear regression and interactions between delirium and pathologic burden were assessed. Outcomes: Change in Mini-Mental State Examination (MMSE) scores during the 6 years before death. Results: There were 987 participants (290 from Vantaa 85+, 241 from the Cambridge City Over-75s Cohort, and 456 from the Cognitive Function and Ageing Study) with neuropathologic data; mean (SD) age at death was 90 (6.4) years, including 682 women (69%). The mean MMSE score 6 years before death was 24.7 points. The 279 individuals with delirium (75% women) had worse initial scores (−2.8 points; 95% CI, −4.5 to −1.0; P < .001). Cognitive decline attributable to delirium was −0.37 MMSE points per year (95% CI, −0.60 to −0.13; P < .001). Decline attributable to the pathologic processes of dementia was −0.39 MMSE points per year (95% CI, −0.57 to −0.22; P < .001). However, the combination of delirium and the pathologic processes of dementia resulted in the greatest decline, in which the interaction contributed an additional −0.16 MMSE points per year (95% CI, −0.29 to −0.03; P = .01). The multiplicative nature of these variables resulted in individuals with delirium and the pathologic processes of dementia declining 0.72 MMSE points per year faster than age-, sex-, and educational level–matched controls. Conclusions and Relevance: Delirium in the presence of the pathologic processes of dementia is associated with accelerated cognitive decline beyond that expected for delirium or the pathologic process itself. These findings suggest that additional unmeasured pathologic processes specifically relate to delirium. Age-related cognitive decline has many contributors, and these findings at the population level support a role for delirium acting independently and multiplicatively to the pathologic processes of classic dementia

Association of Delirium With Cognitive Decline in Late Life: A Neuropathologic Study of 3 Population-Based Cohort Studies

Importance: Delirium is associated with accelerated cognitive decline. The pathologic substrates of this association are not yet known, that is, whether they are the same as those associated with dementia, are independent, or are interrelated. Objective: To examine whether the accelerated cognitive decline observed after delirium is independent of the pathologic processes of classic dementia. Design, Setting, and Participants: Harmonized data from 987 individual brain donors from 3 observational cohort studies with population-based sampling (Vantaa 85+, Cambridge City Over-75s Cohort, Cognitive Function and Ageing Study) performed from January 1, 1985, through December 31, 2011, with a median follow-up of 5.2 years until death, were used in this study. Neuropathologic assessments were performed with investigators masked to clinical data. Data analysis was performed from January 1, 2012, through December 31, 2013. Clinical characteristics of brain donors were not different from the rest of the cohort. Outcome ascertainment was complete given that the participants were brain donors. Exposures: Delirium (never vs ever) and pathologic burden of neurofibrillary tangles, amyloid plaques, vascular lesions, and Lewy bodies. Effects modeled using random-effects linear regression and interactions between delirium and pathologic burden were assessed. Outcomes: Change in Mini-Mental State Examination (MMSE) scores during the 6 years before death. Results: There were 987 participants (290 from Vantaa 85+, 241 from the Cambridge City Over-75s Cohort, and 456 from the Cognitive Function and Ageing Study) with neuropathologic data; mean (SD) age at death was 90 (6.4) years, including 682 women (69%). The mean MMSE score 6 years before death was 24.7 points. The 279 individuals with delirium (75% women) had worse initial scores (-2.8 points; 95% CI, -4.5 to -1.0; P < .001). Cognitive decline attributable to delirium was -0.37 MMSE points per year (95% CI, -0.60 to -0.13; P < .001). Decline attributable to the pathologic processes of dementia was -0.39 MMSE points per year (95% CI, -0.57 to -0.22; P < .001). However, the combination of delirium and the pathologic processes of dementia resulted in the greatest decline, in which the interaction contributed an additional -0.16 MMSE points per year (95% CI, -0.29 to -0.03; P = .01). The multiplicative nature of these variables resulted in individuals with delirium and the pathologic processes of dementia declining 0.72 MMSE points per year faster than age-, sex-, and educational level-matched controls. Conclusions and Relevance: Delirium in the presence of the pathologic processes of dementia is associated with accelerated cognitive decline beyond that expected for delirium or the pathologic process itself. These findings suggest that additional unmeasured pathologic processes specifically relate to delirium. Age-related cognitive decline has many contributors, and these findings at the population level support a role for delirium acting independently and multiplicatively to the pathologic processes of classic dementia.The Cambridge Brain Bank Laboratory (which processed all the CC75C and some of the CFAS cases) is supported by the National Institute for Health Research Cambridge BioMedical Research Centre. The original Epidemiological Clinicopathological Studies in Europe (EClipSE) harmonization project was established through grant RHAG/094 from the Bupa UK Foundation and a European Union Marie Curie International Incoming Fellowship (Dr Keage). Dr Fleming is supported by grant RHAG/058 from the Bupa UK Foundation, which included the latest CC75C fieldwork funding. Dr Davis is supported by grants 090661/Z/09/Z and 107467/Z/15/Z from the Wellcome Trust. Drs Davis and MacLullich are members of The University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, part of the cross-council Lifelong Health and Wellbeing Initiative funded by grant G0700704/84698. Funding from the Biotechnology and Biological Sciences Research Council, Engineering and Physical Sciences Research Council, Economic and Social Research Council, and the Medical Research Council is gratefully acknowledged. Dr Keage is supported by Australian National Health and Medical Research Council Fellowship grant 568890. Dr Cunningham is supported by grant 09/09/07 from the Wellcome Trust Senior Research Fellowship

Cross-Sectional Study of Sleep Quantity and Quality and Amnestic and Non-Amnestic Cognitive Function in an Ageing Population: The English Longitudinal Study of Ageing (ELSA)

Background The aim was to investigate the association between sleep disturbances and cognitive function in younger and older individuals from an ageing population. Methods 3,968 male and 4,821 female white participants, aged 50 years and over, from the English Longitudinal Study of Ageing (ELSA) were studied. Information on sleep quality and quantity as well as both amnestic (memory, ACF) and non-amnestic (non-memory, nACF) function was available at Wave 4 (2008). Analysis of covariance was used to evaluate the relationship between sleep and cognitive function. Results After adjustment for multiple confounders in the younger group (50–64 years) duration of sleep explained 15.2% of the variance in ACF (p = 0.003) and 20.6% of nACF (p = 0.010). In the older group (65+ years) the estimates were 21.3% (p<0.001) and 25.6% (p<0.001), respectively. For sleep quality, there was a statistically significant association between sleep quality and both ACF (p<0.001) and nACF (p<0.001) in the older age group, but not in the younger age group (p = 0.586 and p = 0.373, respectively; interaction between age and sleep quality in the study sample including both age groups: p<0.001 for ACF and p = 0.018 for nACF). Sleep quality explained between 15.1% and 25.5% of the variance in cognition. The interaction with age was independent of duration of sleep. At any level of sleep duration there was a steeper association between sleep quality and ACF in the older than the younger group. Conclusions The associations between sleep disturbances and cognitive function vary between younger and older adults. Prospective studies will determine the temporal relationships between sleep disturbances and changes in cognition in different age groups

Risk factors for dementia in the ninth decade of life and beyond:A study of the Lothian Birth Cohort 1921

Logistic Regression Analysis with Physical Activity Age Groups. (DOCX 13 kb