Cognitive Decline In Elderly Patients Research Articles

Mitochondrial dysfunction precedes hippocampal IL-1β transcription and cognitive impairments after low-dose lipopolysaccharide injection in aged mice

Acute cognitive impairments termed delirium often occur after inflammatory insults in elderly patients. While previous preclinical studies suggest mitochondria as a target for reducing neuroinflammation and cognitive impairments after LPS injection, fewer studies have evaluated the effects of a low-grade systemic inflammation in the aged brain. Thus, to identify the significance of mitochondrial dysfunction after a clinically relevant systemic inflammatory stimulus, we injected old-aged mice (18–20 months) with low-dose lipopolysaccharide (LPS, 0.04 mg/kg). LPS injection reduced mitochondrial respiration in the hippocampus 24 h after injection (respiratory control ratio [RCR], state3u/state4o; control = 2.82 ± 0.19, LPS = 2.57 ± 0.08). However, gene expression of the pro-inflammatory cytokine IL-1β was increased (RT-PCR, control = 1.00 ± 0.30; LPS = 2.01 ± 0.67) at a more delayed time point, 48 h after LPS injection. Such changes were associated with cognitive impairments in the Barnes maze and fear chamber tests. Notably, young mice were unaffected by low-dose LPS, suggesting that mitochondrial dysfunction precedes neuroinflammation and cognitive decline in elderly patients following a low-grade systemic insult. Our findings highlight mitochondria as a potential therapeutic target for reducing delirium in elderly patients.

Investigating the Potential Shared Molecular Mechanisms between COVID-19 and Alzheimer's Disease via Transcriptomic Analysis.

SARS-CoV-2 caused the COVID-19 pandemic. COVID-19 may elevate the risk of cognitive impairment and even cause dementia in infected individuals; it may accelerate cognitive decline in elderly patients with dementia, possibly in Alzheimer's disease (AD) patients. However, the mechanisms underlying the interplay between AD and COVID-19 are still unclear. To investigate the underlying mechanisms and associations between AD progression and SARS-CoV-2 infection, we conducted a series of bioinformatics research into SARS-CoV-2-infected cells, COVID-19 patients, AD patients, and SARS-CoV-2-infected AD patients. We identified the common differentially expressed genes (DEGs) in COVID-19 patients, AD patients, and SARS-CoV-2-infected cells, and these DEGs are enriched in certain pathways, such as immune responses and cytokine storms. We constructed the gene interaction network with the signaling transduction module in the center and identified IRF7, STAT1, STAT2, and OAS1 as the hub genes. We also checked the correlations between several key transcription factors and the SARS-CoV-2 and COVID-19 pathway-related genes. We observed that ACE2 expression is positively correlated with IRF7 expression in AD and coronavirus infections, and interestingly, IRF7 is significantly upregulated in response to different RNA virus infections. Further snRNA-seq analysis indicates that NRGN neurons or endothelial cells may be responsible for the increase in ACE2 and IRF7 expression after SARS-CoV-2 infection. The positive correlation between ACE2 and IRF7 expressions is confirmed in the hippocampal formation (HF) of SARS-CoV-2-infected AD patients. Our findings could contribute to the investigation of the molecular mechanisms underlying the interplay between AD and COVID-19 and to the development of effective therapeutic strategies for AD patients with COVID-19.

Study on the construction of risk prediction model and efficacy validation of cognitive decline in elderly patients with type 2 diabetes

Study on the construction of risk prediction model and efficacy validation of cognitive decline in elderly patients with type 2 diabetes

Cognitive decline in elderly patients with type 2 diabetes is associated with glycated albumin, ratio of Glycated Albumin to glycated hemoglobin, and concentrations of inflammatory and oxidative stress markers

ObjectiveTo investigate the correlations of cognitive function with glycated albumin (GA), the ratio of GA to glycated hemoglobin (GA/HbA1c), and the concentrations of interleukin-6 (IL-6) and superoxide dismutase (SOD) in elderly patients with type 2 diabetes mellitus (T2DM). MethodsA total of 44 elderly T2DM patients were evaluated for cognitive function using the mini-mental state examination (MMSE) and the Montreal cognitive assessment (MoCA). Patients were then divided into two groups based on the MMSE and MoCA scores: a cognitive dysfunction group and a normal cognitive function group. The correlations of the MMSE and MoCA scores with GA/HbA1c, GA, IL-6, and SOD were analyzed. Logistic regression analysis was used to identify independent influential factors for cognitive dysfunction. The predictive value of GA and GA/HbA1c for cognitive dysfunction in elderly T2DM patients was evaluated by receiver operating characteristic (ROC) curve analysis. ResultsAmong these patients, 28 had cognitive impairment. They had significantly higher GA/HbA1c, increased GA and IL-6 levels, and lower SOD concentrations than the normal cognitive function group (all P < 0.05). GA/HbA1c was negatively correlated with the MMSE (r = −0.430, P = 0.007) and MoCA (r = −0.432, P = 0.007) scores. SOD was positively correlated with the MMSE (r = 0.585, P=0.014) and MoCA (r = 0.635, P=0.006) scores. IL-6 was negatively correlated with the MoCA score (r = −0.421, P=0.015). Age and GA/HbA1c were independent factors contributing to cognitive dysfunction. The areas under the ROC curves of GA and GA/HbA1c for the diagnosis of cognitive dysfunction were 0.712 and 0.720, respectively. ConclusionsGA and GA/HbA1c are related to cognitive dysfunction in elderly patients with T2DM.

Comparative evaluation of isoflurane and desflurane for postoperative cognitive decline in elderly patients: A prospective observational pilot study.

Approximately 16%-62% of patients undergoing non cardiac surgeries develop postoperative cognitive dysfunction. We compared the incidence of postoperative cognitive dysfunction in older adults aged 60-80 years who underwent open abdominal surgeries under general anaesthesia using isoflurane or desflurane and correlated it with the serum concentration of interleukin 1, interleukin 6, tumour necrosis factor alpha, amyloid β and S100 on postoperative day 3. Forty American Association of Anesthesiologists Physical Classification I or II patients were included after acquiring institutional ethics committee approval, registering in the Clinical Trials Registry - India, and informed written consent. They underwent open abdominal surgery under general anaesthesia and epidurals between 2017 and 2019. Patients with substance abuse or any disorder affecting cognition were excluded. Postoperative cognitive dysfunction was assessed by Stroop test, Wisconsin Card Sorting Test, Trail making test - B, Porteus Maze test, PGI memory scale, mini-mental state examination, and Bender Gestalt test the day before surgery and on the third postoperative day along with blood samples. Thirty-seven percent of the patients developed postoperative cognitive dysfunction. The risk was similar to isoflurane in comparison with desflurane (risk ratio: 0.65, 95% confidence interval: 0.30, 1.40). A significant percentage increase in reaction time for Porteus Maze test and Trail making test - B was noted with isoflurane (6.69 (4.20-8.94) and 8.01 (2.08-12.5), respectively) in comparison with desflurane group (13.01 (9.09-17.33), p = 0.003 and 11.62 (7.5-17.5), p = 0.017, respectively). Isoflurane and desflurane had a similar impact on the elderly for developing postoperative cognitive dysfunction and no correlation with any of the biomarkers used in the study on postoperative day 3.

Inferring Personalized Treatment Effect of Antihypertensives on Alzheimer's Disease Using Deep Learning.

Alzheimer's disease (AD) is one of the leading causes of death in the United States, especially among the elderly. Recent studies have shown how hypertension is related to cognitive decline in elderly patients, which in turn leads to increased mortality as well as morbidity. There have been various studies that have looked at the effect of antihypertensive drugs in reducing cognitive decline, and their results have proved inconclusive. However, most of these studies assume the treatment effect is similar for all patients, thus considering only the average treatment effects of antihypertensive drugs. In this paper, we assume that the effect of antihypertensives on the onset of AD depends on patient characteristics. We develop a deep learning method called LASSO-Dragonnet to estimate the individualized treatment effects of each patient. We considered six antihypertensive drugs, and each of the six models considered one of the drugs as the treatment and the remaining as control. Our studies showed that although many antihypertensives have a positive impact in delaying AD onset on average, the impact varies from individual to individual, depending on their various characteristics. We also analyzed the importance of various covariates in such an estimation. Our results showed that the individualized treatment effects of each patient could be estimated accurately using a deep learning method, and that the importance of various covariates could be determined.

Cerebral Amyloid Angiopathy presenting as Cognitive Decline

Cerebral amyloid angiopathy (CAA) is a disorder seen as age advances, characterized by the accumulation of amyloid within the leptomeninges and cerebral blood vessels. Lobar hemorrhages are the most common clinical manifestation seen. Cognitive decline due to repeated cerebral microhemorrhages in one of the rare presentations seen mainly in the elderly. We present here a case of a seventy year old female patient who presented with a one year history of progressive cognitive impairment. She was detected to have CAA on imaging with both cortical microbleeds and extensive superficial siderosis. She was started on cholinesterase inhibitors and antipsychotics for her symptoms. Antiplatelet agents were avoided due to increased risk of hemorrhage. This report highlights the importance of CAA as a cause of cognitive decline in elderly patients and also its therapeutic implications

Obstructive sleep apnoea, nocturnal hypoxaemia, and cognitive decline in elderly patients

Obstructive sleep apnoea, nocturnal hypoxaemia, and cognitive decline in elderly patients

COVID-19 Accelerated Cognitive Decline in Elderly Patients with Pre-Existing Dementia Followed up in an Outpatient Memory Care Facility.

Coronavirus disease 2019 (COVID-19) may affect the cognitive function and activities of daily living (ADL) of elderly patients. This study aimed to establish the COVID-19 effect on cognitive decline and the velocity of cognitive function and ADL changes in elderly patients with dementia followed up in an outpatient memory care facility. In total, 111 consecutive patients (age 82 ± 5 years, 32% males) with a baseline visit before infection were divided into those who had or did not have COVID-19. Cognitive decline was defined as a five-point loss of Mini-Mental State Examination (MMSE) score and ADL comprising basic and instrumental ADL indexes (BADL and IADL, respectively). COVID-19 effect on cognitive decline was weighted for confounding variables by the propensity score, whereas the effect on change in the MMSE score and ADL indexes was analyzed using multivariate mixed-effect linear regression. COVID-19 occurred in 31 patients and a cognitive decline in 44. Cognitive decline was about three and a half times more frequent in patients who had COVID-19 (weighted hazard ratio 3.56, 95% confidence interval 1.50-8.59, p = 0.004). The MMSE score lowered on average by 1.7 points/year, independently of COVID-19, but it lowered twice faster in those who had COVID-19 (3.3 vs. 1.7 points/year, respectively, p < 0.050). BADL and IADL indexes lowered on average less than 1 point/year, independently of COVID-19 occurrence. Patients who had COVID-19 had a higher incidence of new institutionalization than those who did not have the disease (45% versus 20%, p = 0.016, respectively). COVID-19 had a significant impact on cognitive decline and accelerated MMSE reduction in elderly patients with dementia.

Downregulation of Nrf2 in the Hippocampus Contributes to Postoperative Cognitive Dysfunction in Aged Rats by Sensitizing Oxidative Stress and Neuroinflammation.

Postoperative cognitive dysfunction (POCD) is a recognized clinical complication defined by a new cognitive impairment arising after a surgical procedure. Elderly patients are especially vulnerable to cognitive impairment after surgical operations, but the underlying mechanisms remain elusive. Oxidative stress and neuroinflammation in the hippocampus, a brain region involved in memory formation, are considered as major contributors to the development of POCD. Activation of nuclear factor erythroid 2-related factor 2 (Nrf2), a master regulator of endogenous inducible defense system, plays a crucial role in protecting cells against oxidative stress and inflammation by enhancing transcription of antioxidant and anti-inflammatory target genes. Here, we examined whether aging downregulates Nrf2 in the hippocampus and, if so, whether downregulation of hippocampal Nrf2 contributes to POCD in aging. Young and aged rats underwent abdominal surgery or sham operation. One week later, cognitive function was assessed, and brains were collected for molecular studies. Compared with young sham rats, aged sham rats exhibited a significant reduction in expression of Nrf2 in the hippocampus. Interestingly, the expression of Nrf2 downstream target genes and levels of reactive oxygen species (ROS) and proinflammatory cytokines in the hippocampus as well as cognitive function were comparable between aged sham and young sham rats. After abdominal surgery, young rats showed significant upregulation of Nrf2 and its target genes in the hippocampus. However, aged rats did not show changes in expression of Nrf2 and its target genes but had increased levels of ROS and proinflammatory cytokines in the hippocampus, along with cognitive impairment as indicated by reduced contextual freezing time. Moreover, upregulation of hippocampal Nrf2 in aged rats with intracerebroventricular infusion of a Nrf2 activator reduced levels of ROS and proinflammatory cytokines in the hippocampus, ameliorating cognitive dysfunction after surgery. The results suggest that aging-induced downregulation of Nrf2 in the hippocampus causes the failure to activate Nrf2-regulated antioxidant defense system in response to surgical insult, which contributes to POCD by sensitizing oxidative stress and neuroinflammation. Nrf2 activation in the brain may be a novel strategy to prevent the cognitive decline in elderly patients after surgery.

Can the Montreal Cognitive Assessment and Mini-Mental State Examination detect cognitive decline in elderly patients with essential tremor?

Objective Given the association between essential tremor (ET) and higher rates of cognitive decline, assessing this decline is an important element of research and clinical care. The Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) are two broad, brief measures that are widely used to monitor cognitive impairment in various neurological disorders. We sought to determine the relative ability of the MoCA and the MMSE to detect cognitive decline in elderly patients with ET. Methods We administered a neuropsychological battery to an ET cohort every 18 months over 4.5 years. We defined the gold standard for change in cognition as the change in neuropsychological test scores over consecutive evaluations and applied the Reliable Change Method to detect meaningful increases/decreases in test scores. We performed receiver operating characteristics (ROC) analysis to quantify the area under the curve (AUC) and compare the ability of the MoCA and the MMSE to detect cognitive decline. Results The AUCs for the MoCA and the MMSE did not differ significantly at any interval or when all intervals were pooled for analysis. Across all intervals, the ability of the MoCA and the MMSE to detect cognitive decline was consistently fair or poor. Conclusions We found that the ability of the MoCA and the MMSE to detect cognitive decline in ET patients over 18-month intervals is inadequate. Unchanged scores on the MoCA and the MMSE in ET over time should be approached with caution. We propose that these screening tools should be supplemented with additional neuropsychological tests.

The Association Between Systemic Immune-Inflammation Index and Postoperative Cognitive Decline in Elderly Patients.

PurposePostoperative cognitive decline (POCD) is highly prevalent in elderly patients who received surgery. The systemic immune-inflammation index (SII) has been shown to be an independent predictor of many diseases associated with inflammation, but the relationship between the SII and POCD is unknown. We aimed to investigate the association between POCD and SII levels to examine the potential of SII in predicting POCD in elderly patients.Patients and MethodsThe present study was carried out among elderly patients who underwent elective orthopedics operation in our hospital, and SII, neutrophil to lymphocyte ratio (NLR), monocyte to lymphocyte ratio (MLR) were calculated from the admission blood sample. POCD was measured by Mini-mental State Examination (MMSE) in elderly patients. The association between SII levels and POCD was analyzed by binary logistic regression analysis.ResultsFinally, 19 (25%) of 76 patients were diagnosed with POCD. Compared with Non-POCD patients, POCD patients showed significantly higher levels of NLR, MLR, SII, especially SII at admission. SII was independently associated with the occurrence of POCD through the logistic regression analysis. Receiver operating characteristic curve analysis indicated that preoperative SII was a significant predictor for POCD, and the area under the curve was 0.909.ConclusionOur data suggest that preoperative NLR, MLR, SII levels in the blood are related to the occurrence of POCD. Preoperative SII level is a prognostic biomarker of POCD in elderly patients after orthopedics operation. More clinical studies are needed to further verify the value of SII in POCD.

Short Sleep Duration on the Night Before Surgery Is Associated With Postoperative Cognitive Decline in Elderly Patients: A Prospective Cohort Study.

As the world is rapidly aging, and the number of elderly patients who undergo surgery is rising, postoperative cognitive decline among those patients has become an increasing healthcare problem. Although understanding the risk factors and mechanisms underlying the pathogenesis of postoperative cognitive decline is critically important from a preventative viewpoint, such knowledge and evidence are lacking. A growing body of evidence suggest an association between cognitive function and sleep duration. The purpose of this study was to investigate the association between postoperative cognitive function and sleep duration on the night before surgery using a wearable sleep tracker. In this 6-month prospective cohort study, we analyzed data from 194 patients aged ≥ 65 years who underwent elective non-cardiac and non-cranial surgery under general anesthesia. According to the sleep duration on the night before surgery, patients were categorized into following four groups: <5, 5–7, 7–9, and >9 h. Perioperative cognitive function and domains were assessed using a neuropsychological test battery, and the incidence and prevalence of cognitive decline over 6 months after surgery were analyzed using the multiple logistic regression analysis. During the 6-month follow-up period, 41 patients (21%) developed cognitive decline. The incidence of cognitive decline was significantly elevated for the patients with sleep duration < 5 h (vs. 7–9 h; surgical duration-adjusted odds ratio, 3.50; 95% confidence interval, 1.20–10.2; P < 0.05). The association between sleep duration and prevalence of cognitive decline was limited to the early postoperative period (at 1 week and 1 month). Among the cognitive domains assessed, attentional function was significantly impaired in patients with a sleep duration < 5 h [vs. 7–9 h at 1 week; 4/37 (10.8%) vs. 0/73 (0%); P < 0.05]. In conclusion, sleep duration < 5 h on the night before surgery was significantly associated with worse attentional function after surgery and higher incidence of cognitive decline. The present results indicate that sleep deprivation on the night before surgery may have a temporary but significantly negative influence on the patient's postoperative cognitive function and is a potential target for preventing cognitive decline.

Aspirin, NOACs, warfarin: which is the best choice to tackle cognitive decline in elderly patients? Insights from the GIRAF and ASCEND-Dementia trials presented at the AHA 2021.

Aspirin, NOACs, warfarin: which is the best choice to tackle cognitive decline in elderly patients? Insights from the GIRAF and ASCEND-Dementia trials presented at the AHA 2021.

Brain Atrophy in First-Episode Psychosis of the Elderly Is Associated With Cognitive Decline.

Objective: To study brain atrophy and cognitive decline in elderly patients with first-episode psychosis (FEP).Methods: Elderly patients aged ≥ 60 years with FEP and onset of psychotic symptoms of ≤ 1 year remitted to the Helsinki University Hospital from December 2009 to December 2011 were included in the study. Diagnoses were made using DSM-IV-TR criteria. All patients had a brain scan, magnetic resonance imaging, or computed tomography. Cognitive performance was assessed using the Consortium to Establish a Registry for Alzheimer`s Disease cognitive test battery.Results: Of the 85 patients with FEP, 18 had very late-onset schizophrenia-like psychosis (VLOSP), 20 had delusional psychosis, 12 had depressive psychosis, and 35 had psychosis due to a general medical condition. Fifteen of the patients had an earlier history of schizophrenia not known at the time of admittance. These patients were analyzed separately. A vast majority of the FEP patients in all diagnostic groups exhibited signs of cortical atrophy, which was associated with early stage cognitive decline. Multivariate analyses showed that brain atrophy was associated with a decline in Mini-Mental State Examination, Clock Drawing Test, and verbal fluency scores in FEP patients.Conclusions: Brain atrophy is a frequent finding in elderly FEP patients and is associated with cognitive decline. Elderly patients with FEP should always undergo brain atrophy and cognition screening, as they may constitute an etiologic factor in such patients.

Screening for subjective cognitive decline in the elderly via subjective cognitive complaints and informant-reported questionnaires: a systematic review

BackgroundSubjective cognitive decline may represent at-risk persons progressing to mild cognitive impairment (MCI), which can be exacerbated by effects of anesthesia and surgery. The objective of this systematic review is to identify the most common questions in subjective cognitive complaint and informant-reported questionnaires used in assessing cognitive impairment of elderly patients that are correlated with standardized tests for cognitive impairment screening.MethodsWe searched Medline, PubMed, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database, Emcare Nursing, Web of Science, Scopus, CINAHL, ClinicalTrials.Gov, and ICTRP between September 20, 2005 to August 31, 2020. We included studies that evaluated subjective cognitive complaints and informant-reported questions in elderly patients.Results and conclusionA total of 28,407 patients were included from 22 studies that assessed 21 subjective complaint questionnaires and nine informant-reported questionnaires. The most common subjective cognitive complaints were those assessing anterograde memory, closely followed by perceptual-motor function and executive function. The most common informant-reported questions were those assessing executive function, temporal orientation, and anterograde memory. Questions assessing learning and memory were most associated with results from standardized tests assessing cognitive impairment. Assessing learning and memory plays a key role in evaluating subjective cognitive decline in elderly patients. Delivering subjective cognitive complaints questions to elderly patient preoperatively may aid in screening for those exhibiting cognitive signs, and in turn are at risk of postoperative complications. Thus, the results from this review contribute to knowledge for healthcare professionals regarding the use of subjective cognitive complaints and informant-reported complaints in preoperative settings.

Comparison of Postoperative Cognitive Decline Using the Mini-Mental State Examination and Montreal Cognitive Assessment After Minor Elective Surgery in Elderly.

Introduction and aimPostoperative cognitive dysfunction (POCD) is an important complication associated with increased morbidity, mortality, and reduced quality of life. Generally, studies have focused on major surgery so there is little evidence of the incidence of cognitive dysfunction in minor surgery. We aimed to compare the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) in terms of detecting cognitive decline in elderly patients after elective inguinal herniorrhaphy procedure with general or spinal anesthesia.Material and methodsThis observational study was conducted from June 2014 to March 2015 at Ankara Numune Education and Research Hospital. The type of anesthesia was determined according to the anesthesiologist’s preference who is blind to the study. Patients were grouped according to anesthesia received: general or spinal anesthesia. The MMSE and MoCA were evaluated presurgery and 24 hours after the operation.ResultsThe postoperative (24th hour) MMSE scores of patients (26.23±2.77) were significantly lower than the preoperative scores (27.17±1.93) in only the general anesthesia group (p =0.003). The postoperative (24th hour) MoCA scores (22.87±3.88 for general and 23.13±4.08 for spinal anesthesia) were significantly lower than the preoperative scores (24.32±3.19 for general and 24.35±2.84 for spinal anesthesia) in both the general and spinal anesthesia groups (p =0.000 and 0.019, respectively). The incidence of postoperative cognitive dysfunction was 32.9% using the MoCA and 15.2% using the MMSE (p=0,018).ConclusionEarly POCD is an important problem after elective minor surgeries, even with spinal anesthesia, in elderly patients. The MoCA is an alternative tool that can be more sensitive than the MMSE to identify cognitive decline in elderly patients undergoing minor surgeries under both general and spinal anesthesia.

Atrial fibrillation burden and cognitive decline in elderly patients undergoing continuous monitoring

To study the relationship between subclinical atrial fibrillation (AF) and changes in cognitive function in a large cohort of individuals with stroke risk factors. Individuals with no prior AF diagnosis but with risk factors for stroke were recruited to undergo annual cognitive assessment with the Montreal Cognitive Assessment (MoCA) along with implantable loop recorder (ILR) monitoring for AF for 3 years. If AF episodes lasting ≥6 minutes were detected, oral anticoagulation (OAC) treatment was initiated. A total of 1194 participants (55.2 % men, mean age 74.5 (±3.9)) had a combined duration of heart rhythm monitoring of ≈1.3 million days. Among these, 339 participants (28.3%) had adjudicated AF, with a median AF burden of 0.072% (0.02, 0.39), and 324 (96%) initiated OAC. When stratifying the participants into AF burden groups (No AF, AFlow (AF burden <0.25%), and AFhigh, (AF burden >0.25%)), only participants in the AFlow group had a decrease in MoCA score over time (P=.03), although this was not significant after adjustment for stroke risk factors. A subgroup analysis of 175 participants (14.6%) with a MoCA <26 at 3 years found no association to AF diagnosis or burden. In a high-risk population, subclinical AF detected by continuous monitoring and subsequently treated with OAC was not associated with a significant change in MoCA score over a 3-year period.

Post-infection cognitive impairments in a cohort of elderly patients with COVID-19

BackgroundUnderstanding the long-term effects of coronavirus disease 2019 (COVID-19) on cognitive function is essential for monitoring the cognitive decline in the elderly population. This study aims to assess the current cognitive status and the longitudinal cognitive decline in elderly patients recovered from COVID-19.MethodsThis cross-sectional study recruited 1539 COVID-19 inpatients aged over 60 years who were discharged from three COVID-19-designated hospitals in Wuhan, China, from February 10 to April 10, 2020. In total, 466 uninfected spouses of COVID-19 patients were selected as controls. The current cognitive status was assessed using a Chinese version of the Telephone Interview of Cognitive Status-40 (TICS-40) and the longitudinal cognitive decline was assessed using an Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Cognitive assessments were performed 6 months after patient discharge.ResultsCompared with controls, COVID-19 patients had lower TICS-40 scores and higher IQCODE scores [TICS-40 median (IQR): 29 (25 to 32) vs. 30 (26 to 33), p < 0.001; IQCODE median (IQR): 3.19 (3.00 to 3.63) vs. 3.06 (3.00 to 3.38), p < 0.001]. Severe COVID-19 patients had lower TICS-40 scores and higher IQCODE scores than non-severe COVID-19 patients [TICS-40 median (IQR): 24 (18 to 28) vs. 30 (26 to 33), p < 0.001; IQCODE median (IQR): 3.63 (3.13 to 4.31) vs. 3.13 (3.00 to 3.56), p < 0.001] and controls [TICS-40 median (IQR): 24 (18 to 28) vs. 30 (26 to 33), p < 0.001; IQCODE median (IQR) 3.63 (3.13 to 4.31) vs. 3.06 (3.00 to 3.38), p < 0.001]. Severe COVID-19 patients had a higher proportion of cases with current cognitive impairment and longitudinal cognitive decline than non-severe COVID-19 patients [dementia: 25 (10.50 %) vs. 9 (0.69 %), p < 0.001; Mild cognitive impairment (MCI): 60 (25.21 %) vs. 63 (4.84 %), p < 0.001] and controls [dementia: 25 (10.50 %) vs. 0 (0 %), p < 0.001; MCI: 60 (25.21 %) vs. 20 (4.29 %), p < 0.001)]. COVID-19 severity, delirium and COPD were risk factors of current cognitive impairment. Low education level, severe COVID-19, delirium, hypertension and COPD were risk factors of longitudinal cognitive decline.ConclusionsSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with an increased risk of long-term cognitive decline in elderly population. COVID-19 patients, especially severe patients, should be intensively monitored for post-infection cognitive decline.

The contribution of beta-amyloid to dementia in Lewy body diseases: a 1-year follow-up study.

Dementia in Lewy Body Diseases (Parkinson’s disease and dementia with Lewy Bodies) affects progression of disabilities, quality of life and well-being. Understanding its pathogenetic mechanisms is critical to properly implement disease-modifying strategies. It has been hypothesized that synuclein- and amyloid-pathology act synergistically aggravating cognitive decline in elderly patients but their precise contribution to dementia is debated. In this study, we aimed at exploring if presence of amyloid deposits influences clinical, cognitive and neuroanatomical correlates of mental decline in a cohort of 40 Parkinson’s disease patients with normal cognition (n = 5), mild cognitive impairment (n = 22), and dementia (n = 13) as well as in Dementia with Lewy Bodies (n = 10). Patients underwent simultaneous 3 T PET/MRI with [18F]-flutemetamol and were assessed with an extensive baseline motor and neuropsychological examination, which allowed level II diagnosis of mild cognitive impairment and dementia. The role of amyloid positivity on each cognitive domain, and on the rate of conversion to dementia at 1-year follow-up was explored. A Kaplan Meier and the Log Rank (Mantel–Cox) test were used to assess the pairwise differences in time-to-develop dementia in Parkinson’s disease patients with and without significant amyloidosis. Furthermore, the presence of an Alzheimer’s dementia-like morphological pattern was evaluated using visual and automated assessment of T1-weighted and T2-weighted MRI images. We observed similar percentage of amyloid deposits in Parkinson’s disease dementia and dementia with Lewy Bodies cohorts (50% in each group) with an overall prevalence of 34% of significant amyloid depositions in Lewy Body Diseases. PET amyloid positivity was associated with worse global cognition (Montreal Cognitive Assessment and Mini Mental State Examination), executive and language difficulties. At 12-month follow-up, amyloid positive Parkinson’s disease patients were more likely to have become demented than those without amyloidosis. Moreover, there was no difference in the presence of an Alzheimer’s disease-like atrophy pattern and in vascular load (at Fazekas scale) between Lewy Body Diseases with and without significant amyloid deposits. Our findings suggest that in Lewy Body Diseases, amyloid deposition enhances cognitive deficits, particularly attention-executive and language dysfunctions. However, the large number of patients without significant amyloid deposits among our cognitively impaired patients indicates that synuclein pathology itself plays a critical role in the development of dementia in Lewy Body Diseases.