cognitive decline
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2022 ◽  
Vol 97 ◽  
pp. 56-61
Zhenxu Xiao ◽  
Xue Ren ◽  
Qianhua Zhao ◽  
Wanqing Wu ◽  
Xiaoniu Liang ◽  

2091 ◽  
Vol 3 (1) ◽  
Srdjan M Vlajkovic ◽  
Belinda RongXin Han ◽  
Peter R Thorne

2022 ◽  
Vol 17 (1) ◽  
Zrinka Požgain ◽  
Grgur Dulić ◽  
Goran Kondža ◽  
Siniša Bogović ◽  
Ivan Šerić ◽  

Abstract Background Postoperative cognitive decline following cardiac surgery is one of the frequently reported complications affecting postoperative outcome, characterized by impairment of memory or concentration. The aetiology is considered multifactorial and the research conducted so far has presented contradictory results. The proposed mechanisms to explain the cognitive decline associated with cardiac surgery include the neurotoxic accumulation of β-amyloid (Aβ) proteins similar to Alzheimer's disease. The comparison of coronary artery bypass grafting procedures concerning postoperative cognitive decline and plasmatic Aβ1-42 concentrations has not yet been conducted. Methods The research was designed as a controlled clinical study of patients with coronary artery disease undergoing surgical myocardial revascularization with or without the use of a cardiopulmonary bypass machine. All patients completed a battery of neuropsychological tests and plasmatic Aβ1-42 concentrations were collected. Results The neuropsychological test results postoperatively were significantly worse in the cardiopulmonary bypass group and the patients had larger shifts in the Aβ1-42 preoperative and postoperative values than the group in which off-pump coronary artery bypass was performed. Conclusions The conducted research confirmed the earlier suspected association of plasmatic Aβ1-42 concentration to postoperative cognitive decline and the results further showed that there were less changes and lower concentrations in the off-pump coronary artery bypass group, which correlated to less neurocognitive decline. There is a lot of clinical contribution acquired by this research, not only in everyday decision making and using amyloid proteins as biomarkers, but also in the development and application of non-pharmacological and pharmacological neuroprotective strategies.

Kelly Virecoulon Giudici ◽  
Sophie Guyonnet ◽  
John E Morley ◽  
Andrew D Nguyen ◽  
Geetika Aggarwal ◽  

Abstract This study aimed to investigate the interaction between weight loss (WL) and plasma amyloid-β42/40 (Aβ42/40), neurofilament light chain (NfL), progranulin, and their association with cognitive decline over time among older adults. This 5-year observational approach included 470 participants from the Multidomain Alzheimer Preventive Trial (MAPT), mean age 76.8y (SD=4.5), 59.4% women. WL was defined as ≥5% decrease over the first year. Biomarkers were measured at 12 months. Cognitive function was assessed yearly from 12 months onwards by Mini-Mental State Examination (MMSE); Clinical Dementia Rating sum of boxes (CDR-SB); a composite score based on Category Naming Test, Digit Symbol Substitution Test, ten MMSE orientation items (MMSEO) and Free and total recall of the Free and Cued Selective Reminding test; and these tests individually. Twenty-seven participants (5.7%) presented WL. In adjusted analyses, combined WL+lower Aβ42/40 (≤0.103, lowest quartile) was related with more pronounced 4-year cognitive decline according to CDR-SB (p<0.0001) and MMSEO (p=0.021), compared to non-WL+higher Aβ42/40. WL+higher NfL (>94.55pg/mL, highest quartile) or progranulin (>38.4ng/mL, three higher quartiles) were related with higher cognitive decline according to CDR-SB, MMSE, MMSEO and composite score (all p<0.03), compared to non-WL+lower NfL or higher progranulin. Regrouping progranulin quartiles (Q1-Q3 vs. Q4) revealed higher cognitive decline among the WL+lower progranulin group compared to non-WL+lower progranulin. In conclusion, 1-year WL was associated with subsequent higher 4-year cognitive decline among older adults presenting low Aβ42/40 or high NfL. Future studies combining plasma biomarker assessments and body weight surveillance may be useful for identifying people at risk of cognitive impairment.

Isabelle Pitrou ◽  
Helen-Maria Vasiliadis ◽  
Carol Hudon

Abstract Objective To examine the associations between BMI categories and subsequent 3-year cognitive decline among older adults, and to test whether physical activity modifies the associations. Methods Study sample included n = 1028 cognitively unimpaired older adults participating in the Étude sur la Santé des Aînés (ESA)-Services longitudinal study and followed 3 years later. Cognitive decline was defined as a decrease of > 3 points in MMSE scores between baseline and follow-up. BMI categories (normal weight (reference), underweight, overweight, obese) were derived from self-reported weight and height. Moderate to vigorous physical activity of ≥20 min (# of times per week) was self-reported. The presence of chronic disorders was ascertained from administrative and self-reported data. Logistic regression analyses were used to study the risk of cognitive decline associated with BMI categories stratified by weekly physical activity (≥140 min), the presence of metabolic, cardiovascular and anxio-depressive disorders. Results In the overall sample, there was no evidence that underweight, overweight, or obesity, as compared to normal weight, was associated with cognitive decline, after adjusting for sociodemographic, lifestyle factors, and comorbidities. Individuals with overweight reporting high physical activity had lower odds of cognitive decline (OR = 0.25, 95% CI = 0.07–0.89), whereas no association was observed in individuals with overweight reporting low physical activity (OR = 0.85, 95% CI = 0.41–1.75). Among participants with metabolic and cardiovascular disorders, individuals with overweight reporting high physical activity had lower odds of cognitive decline (OR = 0.09, 95% CI = 0.01–0.59 and OR = 0.03, 95% CI = 0.01–0.92 respectively), whereas no association was observed in those with low physical activity. Conclusion Physical activity modifies the association between overweight and cognitive decline in older adults overall, as in those with metabolic and cardiovascular disorders. Results highlight the importance of promoting and encouraging regular physical activity in older adults with overweight as prevention against cognitive decline.

2022 ◽  
Christiana Bjorkli ◽  
Mary Hemler ◽  
Joshua Julian ◽  
Axel Sandvig ◽  
Ioanna Sandvig

All disease-targeting drug trials completed to date have fallen short of meeting the clinical endpoint of significantly slowing cognitive decline in Alzheimer′s disease patients. Even the recently approved drug Aducanumab, has proven effective in removing amyloid-β, but does not reduce cognitive decline. This emphasizes the urgent need for novel therapeutic approaches that could reduce several AD neuropathologies simultaneously, eventually leading to improved cognitive performance. To validate whether our mouse model replicates AD neuropathology as observed in patients, we characterized the 3xTg AD mouse model to avoid premature translation of successful results. In this study we have repurposed two FDA-approved drugs, Fasudil and Lonafarnib, targeting the Wnt signaling and endosomal-lysosomal pathway respectively, to test their potential to attenuate AD pathology. Using intracerebral microdialysis, we simultaneously infused these disease-targeting drugs between 1-2 weeks, separately and also in combination, while collecting cerebrospinal fluid. We found that Fasudil reduces intracellular amyloid-β in young, and amyloid plaques in old animals, and overall cerebrospinal fluid amyloid-β. Lonafarnib reduces tau neuropathology and cerebrospinal fluid tau biomarkers in young and old animals. Co-infusion of both drugs was more effective in reducing intracellular amyloid-β than either drug alone, and appeared to improve contextual memory performance. However, an unexpected finding was that Lonafarnib treatment increased amyloid plaque size, suggesting that activating the endosomal-lysosomal system may inadvertently increase amyloid-β pathology if administered too late in the AD continuum. Taken together, these findings lend support to the application of repurposed drugs to attenuate AD neuropathology at various therapeutic time windows.

2022 ◽  
Vol 13 ◽  
Roos J. Jutten ◽  
Dorene M. Rentz ◽  
Jessie F. Fu ◽  
Danielle V. Mayblyum ◽  
Rebecca E. Amariglio ◽  

Introduction: We investigated whether monthly assessments of a computerized cognitive composite (C3) could aid in the detection of differences in practice effects (PE) in clinically unimpaired (CU) older adults, and whether diminished PE were associated with Alzheimer's disease (AD) biomarkers and annual cognitive decline.Materials and Methods:N = 114 CU participants (age 77.6 ± 5.0, 61% female, MMSE 29 ± 1.2) from the Harvard Aging Brain Study completed the self-administered C3 monthly, at-home, on an iPad for one year. At baseline, participants underwent in-clinic Preclinical Alzheimer's Cognitive Composite-5 (PACC5) testing, and a subsample (n = 72, age = 77.8 ± 4.9, 59% female, MMSE 29 ± 1.3) had 1-year follow-up in-clinic PACC5 testing available. Participants had undergone PIB-PET imaging (0.99 ± 1.6 years before at-home baseline) and Flortaucipir PET imaging (n = 105, 0.62 ± 1.1 years before at-home baseline). Linear mixed models were used to investigate change over months on the C3 adjusting for age, sex, and years of education, and to extract individual covariate-adjusted slopes over the first 3 months. We investigated the association of 3-month C3 slopes with global amyloid burden and tau deposition in eight predefined regions of interest, and conducted Receiver Operating Characteristic analyses to examine how accurately 3-month C3 slopes could identify individuals that showed >0.10 SD annual decline on the PACC-5.Results: Overall, individuals improved on all C3 measures over 12 months (β = 0.23, 95% CI [0.21–0.25], p < 0.001), but improvement over the first 3 months was greatest (β = 0.68, 95% CI [0.59–0.77], p < 0.001), suggesting stronger PE over initial repeated exposures. However, lower PE over 3 months were associated with more global amyloid burden (r = −0.20, 95% CI [−0.38 – −0.01], p = 0.049) and tau deposition in the entorhinal cortex (r = −0.38, 95% CI [−0.54 – −0.19], p < 0.001) and inferior-temporal lobe (r = −0.23, 95% CI [−0.41 – −0.02], p = 0.03). 3-month C3 slopes exhibited good discriminative ability to identify PACC-5 decliners (AUC 0.91, 95% CI [0.84–0.98]), which was better than baseline C3 (p < 0.001) and baseline PACC-5 scores (p = 0.02).Conclusion: While PE are commonly observed among CU adults, diminished PE over monthly cognitive testing are associated with greater AD biomarker burden and cognitive decline. Our findings imply that unsupervised computerized testing using monthly retest paradigms can provide rapid detection of diminished PE indicative of future cognitive decline in preclinical AD.

Nutrients ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 333
Matina Kouvari ◽  
Nathan M. D’Cunha ◽  
Nikolaj Travica ◽  
Domenico Sergi ◽  
Manja Zec ◽  

Background: This narrative review presents the association between metabolic syndrome (MetS), along with its components, and cognition-related disorders, as well as the potential reversal role of diet against cognitive impairment by modulating MetS. Methods: An electronic research in Medline (Pubmed) and Scopus was conducted. Results: MetS and cognitive decline share common cardiometabolic pathways as MetS components can trigger cognitive impairment. On the other side, the risk factors for both MetS and cognitive impairment can be reduced by optimizing the nutritional intake. Clinical manifestations such as dyslipidemia, hypertension, diabetes and increased central body adiposity are nutrition-related risk factors present during the prodromal period before cognitive impairment. The Mediterranean dietary pattern stands among the most discussed predominantly plant-based diets in relation to cardiometabolic disorders that may prevent dementia, Alzheimer’s disease and other cognition-related disorders. In addition, accumulating evidence suggests that the consumption of specific dietary food groups as a part of the overall diet can improve cognitive outcomes, maybe due to their involvement in cardiometabolic paths. Conclusions: Early MetS detection may be helpful to prevent or delay cognitive decline. Moreover, this review highlights the importance of healthy nutritional habits to reverse such conditions and the urgency of early lifestyle interventions.

2022 ◽  
Micaela E Consens ◽  
Yuxiao Chen ◽  
Vilas Menon ◽  
Yanling Wang ◽  
Julie A Schneider ◽  

Background: Cortical neuron loss is a pathological hallmark of late-onset Alzheimer's disease (AD). However, it remains unclear which neuronal subtypes are most vulnerable to degeneration and contribute most to cognitive decline. Methods: We analyzed postmortem bulk brain RNA-sequencing (RNAseq) data collected from three studies of aging and AD comprising six neocortical regions (704 individuals; 1037 samples). We estimated relative cell type proportions from each brain sample using neuronal subclass-specific marker genes derived from ultra-high depth single-nucleus RNAseq data (snRNAseq). We associated cell type proportions with AD across all samples using mixed-effects mega-analyses. Bulk tissue analyses were complemented by analyses of three AD snRNAseq datasets using the same cell type definitions and diagnostic criteria (51 individuals). Lastly, we identified cell subtype associations with specific neuropathologies, cognitive decline, and residual cognition. Results: In our mega-analyses, we identified the strongest associations of AD with fewer somatostatin (SST) inhibitory neurons (β=-0.48, pbonf=8.98x10-9) and intra-telencephalic (IT) excitatory neurons (β=-0.45, pbonf =4.32x10-7). snRNAseq-based cell type proportion analyses especially supported the association of SST neurons. Analyses of cell type proportions with specific AD-related phenotypes in ROS/MAP consistently implicated fewer SST neurons with greater brain-wide postmortem tau and beta amyloid (β=-0.155, pFDR=3.1x10-4) deposition, as well as more severe cognitive decline prior to death (β=0.309, pFDR=3.9x10-6). Greater IT neuron proportions were associated strongly with improved cognition (β=0.173, pFDR=8.3x10-5) and residual cognition (β=0.175, pFDR=1.2x10-5), but not canonical AD neuropathology. Conclusions: Proportionally fewer SST and IT neurons were significantly associated with AD diagnosis across multiple studies and cortical regions. These findings support seminal work implicating somatostatin and pyramidal neurons in the pathogenesis of AD and improves our current understanding of neuronal vulnerability in AD.

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