Psoas Muscle Area as a Prognostic Factor for Survival in Patients with an Asymptomatic Infrarenal Abdominal Aortic Aneurysm: A Retrospective Cohort Study.

OBJECTIVES: Loss of muscle mass has been associated with poor survival in several surgical patient populations, including those with an abdominal aortic aneurysm (AAA). We wanted to replicate these findings and assess the association between psoas muscle area (PMA) and survival in patients with an asymptomatic AAA. METHODS: Patients with an asymptomatic infrarenal AAA who underwent computed tomography (CT) scanning between January 1, 2007, and December 31, 2013, were included in this single-centre retrospective cohort study. PMA was measured with thresholding on an axial image at the centre level of the third lumbar vertebra. The lowest tertile of PMA in all patients was used as a cutoff value for a low PMA. Then, in separate analyses for conservatively and surgically managed patients, survival was estimated with the Kaplan-Meier method. Differences in survival between patients with and without a low PMA were tested with the log-rank test. RESULTS: Of 228 patients, 104 were managed conservatively and 124 underwent AAA repair. Seventy-seven patients (62%) had an endovascular repair. In these 228 patients, the median PMA was 16.83 cm2, while the cutoff value for low PMA was 14.56 cm2. Patients who were managed conservatively were more often classified as having low PMA (45/104, 43%, vs. 31/124, 25%; p = .004) and were significantly older (mean 73.44 ± 9.05 years vs. 69.03 ± 7.46 years; p < .001). Low PMA was not associated with survival, either in patients managed conservatively, or in those who underwent AAA repair (p = .512 and p = .311, respectively). CONCLUSIONS: The association between low PMA and poor survival could not be replicated; in this study, low PMA was not associated with survival in patients with an asymptomatic AAA. Further research is recommended before PMA can be used for pre-operative risk stratification.

History of Traumatic Brain Injury in Relation to Cognitive Functioning, Memory Complaints, and Brain Structure in Mid-Life.

In this study, we investigated history of traumatic brain injury with loss of consciousness in relation to cognitive functioning, subjective memory complaints, and brain structure in mid-life. This study included 2005 participants (mean age: 47.6 years, standard deviation: 5.0, women: 65%) from the Origins of Alzheimer's Disease Across the Life Course (ORACLE) study between 2017 and 2020. History of traumatic brain injury was defined as at least one lifetime self-reported brain injury with loss of consciousness. Associations of history of traumatic brain injury with (1) cognitive functioning (measured with the 15-Word Learning Test, Stroop Task, Letter-Digit Substitution Test, Word Fluency Test, Purdue Pegboard Test, and Design Organization Test), (2) current subjective memory complaints (present/absent, measured with a survey), and (3) brain structure (total brain volume, frontal and temporal lobe volume, gray matter volume, white matter volume, white matter hyperintensities volume, infarcts, and microbleeds, measured with brain magnetic resonance imaging [MRI]) were assessed using linear or logistical regression models and adjusted for relevant confounders. In total, 250 of 2005 (12%) participants reported a history of traumatic brain injury. Of those who reported the time post-injury (n = 173), most participants (n = 151, 87%) reported that it had occurred >10 years ago. We found no associations between history of traumatic brain injury and any of the cognitive tests. We did find that a history of traumatic brain injury was associated with having mid-life subjective memory complaints (odds ratio [OR]: 1.87; 95% confidence interval [CI]: 1.35, 2.58). This association was also present when investigating only those who reported an injury >10 years ago (OR:1.69; 95% CI: 1.15, 2.50). Additionally, the association was stronger in those with >30 min loss of consciousness (OR: 3.57; 95% CI: 1.48, 8.59) than in those with <30 min loss of consciousness (OR: 1.85; 95% CI: 1.25, 2.74), when compared with those without history of traumatic brain injury. Lastly, we found no associations between history of traumatic brain injury and any of the structural brain MRI outcomes. In conclusion, our study suggests that at least one lifetime traumatic brain injury with loss of consciousness in mid-life is associated with long-term subjective memory complaints, but not with cognitive functioning or brain structure.

The role of cognitive and brain reserve in late-life depressive events: The Rotterdam Study.

BACKGROUND: Cognitive and brain reserve aim to explain individual differences in susceptibility to dementia and may also affect the risk of late-life depressive events. We assessed whether higher cognitive and brain reserve are associated with lower risk of a late-life depressive event. METHODS: This study included 4509 participants from the population-based Rotterdam Study (mean age: 63.4 ± 10.2 years, 55 % women) between 2005 and 2019. Participants completed cognitive testing and brain-MRI at baseline. Cognitive reserve was defined as the common variance across cognitive tests, while adjusting for demographic factors and brain MRI-markers. Brain reserve was defined as total brain volume divided by intracranial volume. Depressive events (depressive symptoms/depressive syndrome/major depressive disorder) were repeatedly measured (follow-up: 6.6 ± 3.9 years) with validated questionnaires, clinical interviews, and follow-up of medical records. Hazard ratios (HR) with 95 % confidence intervals (CI) were estimated using Cox-regressions. RESULTS: Higher cognitive (HR: 0.91/SD, 95%CI: 0.84; 1.00) and brain reserve (HR: 0.88/SD, 95%CI: 0.77; 1.00) were associated with a lower risk of a depressive event after adjustment for baseline depressive symptoms. These associations attenuated when participants with clinically relevant depressive symptoms at baseline were excluded (HR: 0.95/SD, 95%CI: 0.86; 1.05, HR: 0.89/SD, 95%CI: 0.76; 1.03, respectively). LIMITATIONS: No data was available on depression in early-life and the number of participants with major depressive disorder was relatively low (n = 105). CONCLUSIONS: Higher cognitive and brain reserve may be protective factors for late-life depressive events, particularly in those who have experienced clinical relevant depressive symptoms before. Further research is needed to determine whether cognitive and brain reserve could be used as targets for the prevention of late-life depression.

Sociodemographic, Lifestyle, Physical, and Psychosocial Determinants of Cognitive Reserve.

BACKGROUND: Cognitive reserve aims to explain individual differences in the susceptibility to the functional impact of dementia in the presence of equal amount of neuropathological damage. It is thought to be shaped by a combination of innate individual differences and lifetime exposures. Which determinants are associated with cognitive reserve remains unknown. OBJECTIVE: The objective of this study was to investigate the associations of sociodemographic, lifestyle, physical, and psychosocial determinants with cognitive reserve, and potential sex differences. METHODS: This cross-sectional study included 4,309 participants from the Rotterdam Study (mean age 63.9±10.7) between 2006-2016. Participants completed five cognitive tests and a brain MRI-scan. Cognitive reserve was defined as a latent variable that captures variance common across five cognitive tests, while adjusting for demographic and MRI-inferred neuropathological factors. The associations of potential determinants and cognitive reserve, adjusted for relevant confounders, were assessed with structural equation models. RESULTS: Current smoking (adjusted mean difference: -0.31, 95%confidence interval -0.42; -0.19), diabetes mellitus (-0.25, -0.40; -0.10) and depressive symptoms (-0.07/SD, -0.12; -0.03) were associated with a lower cognitive reserve whereas alcohol use (0.07/SD, 0.03; 0.12) was associated with higher cognitive reserve. Only smoking was associated with cognitive reserve in both men and women. Employment, alcohol use, diabetes, history of cancer, COPD, and depressive symptoms were only associated with cognitive reserve in women. CONCLUSION: Our study found that current smoking, diabetes mellitus, and depressive symptoms were associated with a lower cognitive reserve, whereas more alcohol use was associated with a higher cognitive reserve, but with clear differences between men and women.

The interaction of cognitive and brain reserve with frailty in the association with mortality: an observational cohort study.

BACKGROUND: A higher cognitive reserve and brain reserve could decrease mortality risk, but the interaction of these factors with general age-related loss of physical fitness (eg, frailty) remains unclear with regards to mortality. We investigated the associations of cognitive and brain reserve with mortality and the interaction of cognitive and brain reserve with frailty within these associations. METHODS: Within the observational population-based cohort of the Rotterdam Study, we included participants who visited the research centre for a cognitive assessment between March 2, 2009, and March 1, 2012. Participants with an incomplete assessment of cognition, no data on education attainment, no MRI or an MRI of insufficient quality, three or more missing frailty criteria, or a dementia diagnosis were excluded. Participants were followed up until their death or May 1, 2019. Cognitive reserve was defined as a latent variable that captures variance across five cognitive tests. Brain reserve was defined as the proportion of healthy-appearing brain volume relative to total intracranial volume measured with 1·5 Tesla MRI. Frailty was defined according to Fried's frailty phenotype; participants meeting at least one of the five criteria were considered frail. Hazard ratios (HRs) for associations of cognitive reserve, brain reserve, frailty, and reserve-frailty interactions with the risk of mortality were estimated using Cox regression models. FINDINGS: 2878 individuals in the Rotterdam Study who visited the research centre for a cognitive assessment were considered eligible. 1388 individuals were excluded due to incomplete or missing data or a dementia diagnosis. 1490 participants with valid information on cognitive reserve, brain reserve, and frailty were included (mean age 74·3 years [SD 5·5]; 815 [55%] female participants). 810 (54%) participants were classified as frail. A higher cognitive reserve (HR 0·87 per SD, 95% CI 0·76-0·99, p=0·036) and a higher brain reserve (0·85 per SD, 0·72-1·00, p=0·048) were associated with a lower risk of mortality, after adjusting for sex, age, educational level, body-mass index, smoking status, and number of comorbidities. The association between cognitive reserve and mortality was more pronounced (0·77 per SD, 0·66-0·90, p=0·0012) when the cognitive reserve-frailty interaction (p=0·0078) was included, indicating that higher cognitive reserve is related to lower mortality in individuals with frailty. The brain reserve-frailty interaction was non-significant. INTERPRETATION: Higher cognitive reserve and higher brain reserve were associated with a lower mortality risk. Additionally, cognitive reserve and frailty interact in the association with mortality, such that higher cognitive reserve is particularly associated with lower mortality in frail participants. FUNDING: Netherlands Organization for Health Research and Development and EU Horizon 2020 research programme.

Resistance to developing brain pathology due to vascular risk factors: the role of educational attainment.

Brain pathology develops at different rates between individuals with similar burden of risk factors, possibly explained by brain resistance. We examined if education contributes to brain resistance by studying its influence on the association between vascular risk factors and brain pathology. In 4111 stroke-free and dementia-free community-dwelling participants (62.9 ± 10.7 years), we explored the association between vascular risk factors (hypertension and the Framingham Stroke Risk Profile [FRSP]) and imaging markers of brain pathology (markers of cerebral small vessel disease and brain volumetry), stratified by educational attainment level. Associations of hypertension and FSRP with markers of brain pathology were not significantly different between levels of educational attainment. Certain associations appeared weaker in those with higher compared to lower educational attainment, particularly for white matter hyperintensities (WMH). Supplementary residual analyses showed significant associations between higher educational attainment and stronger resistance to WMH among others. Our results suggest a role for educational attainment in resistance to vascular brain pathology. Yet, further research is needed to better characterize determinants of brain resistance.

The Risk of Dementia in Relation to Cognitive and Brain Reserve.

BACKGROUND: Individual differences in the risk to develop dementia remain poorly understood. These differences may partly be explained through reserve, which is the ability to buffer cognitive decline due to neuropathology and age. OBJECTIVE: To determine how much early and late-life cognitive reserve (CR) and brain reserve (BR) contribute to the risk of dementia. METHODS: 4,112 dementia-free participants (mean age = 66.3 years) from the Rotterdam Study were followed up for on average 6.0 years. Early-life CR and BR were defined as attained education and intracranial volume, respectively. Late-life CR was derived through variance decomposition based on cognition. Late-life BR was set as the total non-lesioned brain volume divided by intracranial volume. RESULTS: Higher early-life CR (hazard ratio = 0.48, 95% CI = [0.21; 1.06]) but not early-life BR associated with a lower risk of incident dementia. Higher late-life CR (hazard ratio = 0.57, 95% CI = [0.48; 0.68]) and late-life BR (hazard ratio = 0.54, 95% CI = [0.43; 0.68]) also showed lower levels of dementia. Combining all proxies into one model attenuated the association between early-life CR and dementia (hazard ratio = 0.56, 95% CI = [0.25; 1.25]) whereas the other associations were unaffected. These findings were stable upon stratification for sex, age, and APOEɛ4. Finally, high levels of late-life CR and BR provided additive protection against dementia. CONCLUSION: The findings illustrate the importance of late-life over early-life reserve in understanding the risk of dementia, and show the need to study CR and BR conjointly.

Unfavorable Outcome in Patients with Aneurysmal Subarachnoid Hemorrhage WFNS Grade I.

BACKGROUND: Patients with an aneurysmal subarachnoid hemorrhage (aSAH) and World Federation of Neurosurgical Societies (WFNS) grade I on admission are generally considered to have a good clinical outcome. OBJECTIVE: The objective of this study was to assess the actual clinical outcome of WFNS grade I aSAH patients, and to determine which factors are associated with unfavourable outcome. METHODS: For this prospective cohort study, 132 consecutive patients (age 18 years or older) with a WFNS grade I aSAH admitted to our hospital between December 2011 and January 2016 were eligible. Clinical outcome was measured using the modified Rankin Scale (mRS) at 6-month follow-up. Unfavorable outcome was defined as an mRS score of 3-6. Univariable analyses were performed using logistic regression models. RESULTS: Of 116 patients, only 5 patients (4%) had an mRS score of 0 and most (65%) had an mRS score of 2. Twenty-five patients (22%) had an unfavorable outcome. Nine (8%) patients died, of whom 4 died during admission. Factors associated with unfavorable outcome were age (per increasing decade: odds ratio [OR]. 1.78; 95% confidence interval [CI], 1.16-2.72), delayed cerebral ischemia (OR, 4.32; 95% CI, 1.63-11.44), pneumonia (OR, 10.75; 95% CI, 1.94-59.46) and meningitis (OR, 28.47; 95% CI, 1.42-571.15). CONCLUSIONS: Despite their neurologically optimal clinical condition on admission, 1 in 5 patients with WFNS grade I aSAH has an unfavorable clinical outcome or is dead at 6-month follow-up. Additional multivariable analysis in larger patient cohorts is necessary to identify the extent to which preventable complications contribute to unfavorable outcomes in these patients.