Cerebral Amyloidosis in Individuals with Subjective Cognitive Decline: From Genetic Predisposition to Actual Cerebrospinal Fluid Measurements.

The possible relationship between Subjective Cognitive Decline (SCD) and dementia needs further investigation. In the present study, we explored the association between specific biomarkers of Alzheimer's Disease (AD), amyloid-beta 42 (Aß42) and Tau with the odds of SCD using data from two ongoing studies. In total, 849 cognitively normal (CN) individuals were included in our analyses. Among the participants, 107 had available results regarding cerebrospinal fluid (CSF) Aß42 and Tau, while 742 had available genetic data to construct polygenic risk scores (PRSs) reflecting their genetic predisposition for CSF Aß42 and plasma total Tau levels. The associations between AD biomarkers and SCD were tested using logistic regression models adjusted for possible confounders such as age, sex, education, depression, and baseline cognitive test scores. Abnormal values of CSF Aß42 were related to 2.5-fold higher odds of SCD, while higher polygenic loading for Aß42 was associated with 1.6-fold higher odds of SCD. CSF Tau, as well as polygenic loading for total Tau, were not associated with SCD. Thus, only cerebral amyloidosis appears to be related to SCD status, either in the form of polygenic risk or actual CSF measurements. The temporal sequence of amyloidosis being followed by tauopathy may partially explain our findings.

Protecting the Brain While Healing Hearts: The Protective Role of Cognitive Reserve in Cardiac Surgery.

OBJECTIVE: One of the most significant complications following coronary artery bypass grafting (CABG) is postoperative cognitive decline (POCD). CABG patients frequently experience considerable postoperative cognitive dysfunction (POCD), including decline in attention, orientation, memory, judgment, and social functioning. DESIGN: These negative effects may potentially be resolved by a protective factor, cognitive reserve (CR) that has been considered to function as a buffer against the consequences of neuropathology. SETTING: We explored the frequency of POCD and CR in coronary artery disease patients undergoing CABG. We hypothesized that high levels of CR would protect against POCD after cardiac surgery. PARTICIPANTS: We assessed 101 patients before surgery, and 4 months after cardiopulmonary bypass surgery with the use of extracorporeal circulation. MEASUREMENTS: Measures of cognitive functions, CR, anxiety, and depression were included in the assessment. RESULTS: Each patient was placed in the high (n = 50) or low CR (n = 51) group, based on median split. Chi-square tests effect showed that patients with low CR were more likely to a great extend to demonstrate postsurgical cognitive decline in attention, memory, visuospatial perception and executive functions than patients with high CR upon postsurgery neuropsychological assessment. CONCLUSIONS: Our results suggest that CR can forecast neuropsychological outcomes of cardiac surgery, recognizing the patients with low CR and help them to participate to interventions programs that could slow cognitive aging or reduce the risk of dementia and enhance their overall postsurgical functional outcome.

Antihypertensive Medication Class and the Risk of Dementia and Cognitive Decline in Older Adults: A Secondary Analysis of the Prospective HELIAD Cohort.

BACKGROUND: It is unclear whether the main antihypertensive medication classes (diuretics, calcium channel blockers, beta-blockers, angiotensin converting enzyme inhibitors, and angiotensin receptor blockers (ARBs)) are associated with different risks of cognitive decline. Published evidence is conflicting and stems mainly from observational studies. OBJECTIVE: To investigate the differential effects of antihypertensives on the risks of developing dementia and cognitive decline, with a specific focus on the vascular component of the mechanisms underlying these interactions. METHODS: Older adults with a history of hypertension and without dementia were drawn from the population-based HELIAD cohort. Age-, gender-, education-, and antihypertensive medication- (five dichotomous exposures) adjusted Cox proportional-hazards models and generalized estimating equations were performed to appraise the associations of baseline antihypertensive therapy with dementia incidence and cognitive decline (quantified using a comprehensive neuropsychological battery). Analyses were subsequently adjusted for clinical vascular risk (dyslipidemia, diabetes mellitus, smoking, cardiovascular, and cerebrovascular history) and genetic susceptibility to stroke (using polygenic risk scores generated according to the MEGASTROKE consortium GWAS findings). RESULTS: A total of 776 predominantly female participants (73.61±4.94 years) with hypertension and a mean follow-up of 3.02±0.82 years were analyzed. Baseline treatment was not associated with the risk of incident dementia. ARB users experienced a slower yearly global cognitive [2.5% of a SD, 95% CI = (0.1, 4.9)] and language [4.4% of a SD, 95% CI = (1.4, 7.4)] decline compared to non-users. The fully adjusted model reproduced similar associations for both global cognitive [ß= 0.027, 95% CI =  (-0.003, 0.057)], and language decline [ß= 0.063, 95% CI = (0.023, 0.104)]. CONCLUSION: ARBs may be superior to other antihypertensive agents in the preservation of cognition, an association probably mediated by vascular-independent mechanisms.

Plasma Glutathione and Prodromal Parkinson's Disease Probability.

BACKGROUND: A decrease in glutathione (GSH) levels is considered one of the earliest biochemical changes in Parkinson's disease (PD). OBJECTIVE: The authors explored the potential role of plasma GSH as a risk/susceptibility biomarker for prodromal PD (pPD) by examining its longitudinal associations with pPD probability trajectories. METHODS: A total of 405 community-dwelling participants (median age [interquartile range] = 73.2 [7.41] years) without clinical features of parkinsonism were followed for a mean (standard deviation) of 3.0 (0.9) years. RESULTS: A 1 µmol/L increase in plasma GSH was associated with 0.4% (95% confidence interval [CI], 0.1%-0.7%; P = 0.017) less increase in pPD probability for 1 year of follow-up. Compared with participants in the lowest GSH tertile, participants in the highest GSH tertile had a 12.9% (95% CI, 22.4%-2.2%; P = 0.020) slower rate of increase of pPD probability for 1 year of follow-up. CONCLUSION: Plasma GSH was associated with pPD probability trajectories; therefore, it might assist in the identification of individuals who are likely to reach the threshold for pPD diagnosis more rapidly. © 2021 International Parkinson and Movement Disorder Society.

Mediterranean Lifestyle in Relation to Cognitive Health: Results from the HELIAD Study.

Many lifestyle factors have been linked to cognitive function but little is known about their combined effect. An overall lifestyle pattern for people living in the Mediterranean basin has been proposed, including diet, but also physical activity, sleep and daily living activities with social/intellectual aspects. We aimed to examine the associations between a combination of these lifestyle factors and detailed cognitive performance. A total of 1716 participants from the Hellenic Longitudinal Investigation of Ageing and Diet (HELIAD), a population-based study of participants ≥65 years, were included in this analysis. Lifestyle factors were evaluated using standard, validated questionnaires and a Total Lifestyle Index (TLI) was constructed. Cognitive outcomes included mild cognitive impairment (MCI) diagnosis, a composite z-score (either continuous or with a threshold at the 25th percentile) and z-scores for five cognitive domains. A higher TLI was associated with 65% reduced odds for MCI in the non-demented individuals and 43% reduced odds for low global cognition when MCI participants were excluded, a risk reduction equivalent to 9 and 2.7 fewer years of ageing, respectively. Each lifestyle factor was differentially associated with domain-specific cognitive performance. Our results suggest that a TLI, more so than single lifestyle parameters, may be related to cognitive performance.

Current standards of neuropsychological assessment in epilepsy surgery centers across Europe.

We explored the current practice with respect to the neuropsychological assessment of surgical epilepsy patients in European epilepsy centers, with the aim of harmonizing and establishing common standards. Twenty-six epilepsy centers and members of "E-PILEPSY" (a European pilot network of reference centers in refractory epilepsy and epilepsy surgery), were asked to report the status of neuropsychological assessment in adults and children via two different surveys. There was a consensus among these centers regarding the role of neuropsychology in the presurgical workup. Strong agreement was found on indications (localization, epileptic dysfunctions, adverse drugs effects, and postoperative monitoring) and the domains to be evaluated (memory, attention, executive functions, language, visuospatial skills, intelligence, depression, anxiety, and quality of life). Although 186 different tests are in use throughout these European centers, a core group of tests reflecting a moderate level of agreement could be discerned. Variability exists with regard to indications, protocols, and paradigms for the assessment of hemispheric language dominance. For the tests in use, little published evidence of clinical validity in epilepsy was provided. Participants in the survey reported a need for improvement concerning the validity of the tests, tools for the assessment of everyday functioning and accelerated forgetting, national norms, and test co-normalization. Based on the present survey, we documented a consensus regarding the indications and principles of neuropsychological testing. Despite the variety of tests in use, the survey indicated that there may be a core set of tests chosen based on experience, as well as on published evidence. By combining these findings with the results of an ongoing systematic literature review, we aim for a battery that can be recommended for the use across epilepsy surgical centers in Europe.

Neurocognitive outcome after coronary artery bypass surgery using minimal versus conventional extracorporeal circulation: a randomised controlled pilot study.

OBJECTIVE: Neurocognitive impairment can be a debilitating complication after cardiac surgery. The aim of this study was to assess the effect of minimal extracorporeal circulation (MECC) versus conventional extracorporeal circulation (CECC) on neurocognitive function after elective coronary artery bypass grafting (CABG) and whether this can be attributed to improved cerebral perfusion intraoperatively. METHODS AND RESULTS: 64 patients scheduled for elective CABG surgery were prospectively randomly assigned to surgical revascularisation with MECC versus CECC. All patients were continuously monitored for changes in cerebral oxygenation with near-infrared spectroscopy during the procedure. Neurocognitive assessment was performed before surgery, on the day of discharge and at 3 months postoperatively using a battery of standardised neurocognitive tests. Both groups were comparable in terms of demographic and clinical data. MECC was associated with improved cerebral perfusion during cardiopulmonary bypass (CPB). Eleven patients operated on with MECC and 17 with CECC experienced at least one episode of cerebral desaturation (38% vs 55%, p=0.04) with similar duration (10 vs 12.3 min, p=0.1). At discharge patients operated on with MECC showed a significantly improved performance on complex scanning, visual tracking, focused attention and long-term memory. At 3 months significantly improved performance was also evident on visuospatial perception, executive function, verbal working memory and short-term memory. Patients operated on with MECC experienced a significantly lower risk of early cognitive decline both at discharge (41% vs 65%, p=0.03) and at 3-month evaluation (21% vs 61%, p<0.01). CONCLUSIONS: Use of MECC attenuates early postoperative neurocognitive impairment after coronary surgery compared with conventional CPB. This finding may have important implications on the surgical management strategy for coronary artery disease. CLINICAL TRIAL REGISTRATION NUMBER: The study is registered at ClinicalTrials.gov, number NCT01213511.

Ruff 2 and 7 Selective Attention Test: normative data, discriminant validity and test-retest reliability in Greek adults.

Rapidly expanding interest in neuropsychological assessment in Greece has made the development of appropriate culture-specific normative data for core neuropsychological measures essential. In the present study, we sought to establish normative, test-retest reliability and discriminant validity data for the Ruff 2 and 7 Selective Attention Test in the Greek adult population. We administered the test using standard procedures to 218 healthy Greek adults (95 men), aged 17-80 years and two adult patient groups (26 detoxified opiate addicts and 23 HIV seropositive individuals). Using linear regression analyses, we examined the contribution of age, education and gender on Ruff 2 and 7 performance. We further examined test-retest reliability by administering the test on two occasions to 40 healthy adults, with an intersession interval of 12-14 weeks. The regression analyses revealed that age and education, but not gender, contributed significantly to participants performance, with older age and lower education contributing to poorer performance on Speed scores, but only education contributing moderately to Automatic Detection Accuracy scores. Test-retest reliability was very high (.94-.98) for Speed scores, and adequate to high (.73-.89) for Accuracy scores. Younger adults also demonstrated larger practice effects compared to older participants. The test appears to discriminate adequately between the performance of detoxified opiate addicts and HIV seropositive patients and matched healthy controls, as both patient groups performed more poorly than their respective control group. We present normative data for Speed and Accuracy scores stratified by age and education for the Greek adult population.