Mini-Mental State Examination Score Research Articles

Neutrophil to lymphocyte ratio in Alzheimer's disease: A systematic review and meta-analysis.

The Neutrophil-to-Lymphocyte Ratio (NLR) is a clinical indicator of peripheral inflammation that is easily accessible. It is worth noting that the formation of amyloid-β (Aβ) plaques and neurofibrillary tangles has been linked to inflammation and immune dysregulation. The main objective of this systematic review and meta-analysis is to comprehensively evaluate the existing body of research concerning the NLR in the context of Alzheimer's disease (AD) and mild cognitive impairment (MCI). We conducted a comprehensive online search and included studies that evaluated the NLR in 1) patients with AD or MCI and 2) healthy control (HC) participants. We also pooled mean and standard deviation (SD) data for each group. Ultimately, 12 studies encompassed 1,309 individuals diagnosed with AD with mean NLR levels of 2.68, 1,929 individuals with MCI with mean NLR levels of 2.42, and 2,064 HC with mean NLR levels of 2.06 were included in this systematic review and meta-analysis. The mean NLR was 0.59 higher in AD patients compared to HC participants (mean difference (MD) = 0.59 [0.38; 0.80]). Similarly, the mean NLR was higher in AD than MCI patients (MD = 0.23 [0.13; 0.33]). Additionally, the mean NLR was higher in individuals with MCI compared to HC participants (MD = 0.37 [0.22; 0.52]). In the subgroup meta-analysis based on the Mini-Mental State Examination (MMSE), AD patients with lower MMSE scores (using a cut-off of 20) exhibited significantly higher mean NLR (3.10 vs. 2.70, with a p-value for subgroup differences < 0.01). The NLR, which serves as a marker of peripheral inflammation, shows increased levels in individuals with AD and MCI compared to HC participants. Furthermore, our study indicates that NLR levels are significantly higher in AD than MCI. Additionally, our novel finding suggests significantly higher NLR levels among AD patients with more severe cognitive decline compared to AD patients with less severe cognitive decline. So, it can be concluded that the higher cognitive decline in humans is accompanied by higher NLR levels. Further longitudinal researches are needed to explore more details about the relationship between inflammation and dementia.

Association of Plasma Amyloid, P-Tau, GFAP, and NfL With CSF, Clinical, and Cognitive Features in Patients With Dementia With Lewy Bodies.

Plasma β-amyloid-1-42/1-40 (Aβ42/40), phosphorylated-tau (P-tau), glial fibrillary acidic protein (GFAP), and neurofilament light (NfL) have been widely examined in Alzheimer disease (AD), but little is known about their reflection of copathologies, clinical importance, and predictive value in dementia with Lewy bodies (DLB). We aimed to evaluate associations of these biomarkers with CSF amyloid, cognition, and core features in DLB. This cross-sectional multicenter cohort study with prospective component included individuals with DLB, AD, and healthy controls (HCs), recruited from 2002 to 2020 with an annual follow-up of up to 5 years, from the European-Dementia With Lewy Bodies consortium. Plasma biomarkers were measured by single-molecule array (Neurology 4-Plex E kit). Amyloid status was determined by CSF Aβ42 concentrations, and cognition was assessed by Mini-Mental State Examination (MMSE). Biomarker differences across groups, associations with amyloid status, and clinical core features were assessed by analysis of covariance. Associations with cognitive impairment and decline were assessed by linear regression and linear mixed-effects models. In our cohort consisting of 562 individuals (HC n = 89, DLB n = 342, AD n = 131; 250 women [44.5%], mean [SD] age of 71 [8] years), sex distribution did not differ between groups. Patients with DLB were significantly older, and had less years of education and worse baseline cognition than HC, but not AD. DLB participants stratified for amyloid status differed significantly in plasma Aβ42/40 ratio (decreased in amyloid abnormal: β = -0.008, 95% CI -0.016 to -0.0003, p = 0.01) and P-tau (increased in amyloid abnormal, P-tau181: β = 0.246, 95% CI 0.011-0.481; P-tau231: β = 0.227, 95% CI 0.035-0.419, both p < 0.05), but not in GFAP (β = 0.068, 95% CI -0.018 to 0.153, p = 0.119), and NfL (β = 0.004, 95% CI -0.087 to 0.096, p = 0.923) concentrations. Higher baseline GFAP, NfL, and P-tau concentrations were associated with lower MMSE scores in DLB, and GFAP and NfL were associated with a faster cognitive decline (GFAP: annual change of -2.11 MMSE points, 95% CI -2.88 to -1.35 MMSE points, p < 0.001; NfL: annual change of -2.13 MMSE points, 95% CI -2.97 to -1.29 MMSE points, p < 0.001). DLB participants with parkinsonism had higher concentrations of NfL (β = 0.08, 95% CI 0.02-0.14, p = 0.006) than those without. Our study suggests a possible utility of plasma Aβ42/40, P-tau181, and P-tau231 as a noninvasive biomarkers to assess amyloid copathology in DLB, and plasma GFAP and NfL as monitoring biomarkers for cognitive symptoms in DLB.

The Effects of mirror therapy in postural and kinesthetic rehabilitation on stance phase of gait in subacute stroke

Background: This study explored the effectiveness of mirror therapy in improving postural and kinesthetic rehabilitation during the stance phase of gait in subacute stroke patients. Given the crucial role of balance and functional recovery in enhancing mobility and overall quality of life in stroke survivors, the primary focus was on these aspects. Objective: The primary objective was to evaluate the impacts of mirror therapy on postural and kinesthetic rehabilitation during the stance phase of gait in subacute stroke patients. Methods: A randomized controlled trial was conducted over nine months in Rahim Yar Khan, involving both private and government hospitals. Sixty-four participants were randomly assigned to two groups: the Conventional+KTR group and the Mirror Therapy group, with 32 participants in each. Inclusion criteria required participants to have a single episode of hemiplegic subacute stroke diagnosed by a neurologist, inclusion of both ischemic and hemorrhagic stroke, and sufficient cognitive ability to follow instructions as indicated by a Mini-Mental State Examination (MMSE) score of 24 or higher. Mild spasticity in all joints of the affected limb was defined by a Modified Ashworth Scale score of less than 3. The intervention for the experimental group involved mirror therapy conducted four days a week for six weeks, supplemented by a home plan for the remaining three days. The control group received conventional therapy, including proprioceptive neuromuscular facilitation (PNF) and electrical interventions, also for four days a week, with a home plan for the remaining days. Key outcome measures were the Berg Balance Scale (BBS) for balance and the Fugl-Meyer Assessment for functional recovery. Data were analyzed using SPSS Version 25, with significance set at p&lt;0.05. Results: The Mirror Therapy group showed significantly greater improvements in balance scores, with a mean BBS of 40.31 at week 6 compared to 36.78 in the Conventional+KTR group (p&lt;0.001). Functional recovery was more pronounced in the Conventional+KTR group, which had a mean Fugl-Meyer Assessment score of 35.63 at week 6 compared to 30.50 in the Mirror Therapy group (p&lt;0.001). Gender distribution was similar across both groups, with the Conventional+KTR group consisting of 21.9% males and 78.1% females, and the Mirror Therapy group having 18.8% males and 81.3% females. Conclusion: Mirror therapy significantly enhances postural and kinesthetic rehabilitation in subacute stroke patients, particularly in improving balance more effectively than Conventional+KTR therapy. Conversely, Conventional+KTR therapy showed better results in functional recovery. These findings suggest that mirror therapy can be a valuable addition to stroke rehabilitation programs, offering a potential avenue for improved patient outcomes. Keywords: Mirror Therapy, Subacute Stroke Rehabilitation, Gait Improvement, Postural Awareness, Kinesthetic Awareness, Berg Balance Scale, Fugl-Meyer Assessment, Randomized Controlled Trial, Stroke Recovery, Balance Rehabilitation.

Relationship Between Mild Cognitive Impairment and Activities of Daily Living in Older Patients in Convalescent Rehabilitation Wards

Aims Rehabilitation is commonly used in older patients with mild cognitive impairment (MCI). This study aimed to determine whether MCI affects the effectiveness of rehabilitation in older patients. Methods This was a retrospective cohort study of patients who received rehabilitation in convalescent rehabilitation wards (CRW) in Japan between January 2021 and December 2022. Results 141 patients who met inclusion criteria were included in this study. The patients were divided into MCI and non-MCI groups based on the Mini Mental State Examination score. At admission, MCI patients were significantly older, and had longer hospital stays, malnutrition, lower grip strength, and lower motor independence measures (FIMS) scores. After propensity score matching to adjust for differences in baseline characteristics, motor FIMS scores at discharge remained lower in the MCI group. Conclusions The presence of MCI is associated with ADL at discharge in older adults admitted to a CRW for rehabilitation.

Predicting Longitudinal Cognitive Decline and Alzheimer's Conversion in Mild Cognitive Impairment Patients Based on Plasma Biomarkers.

The increasing burden of Alzheimer's disease (AD) emphasizes the need for effective diagnostic and therapeutic strategies. Despite available treatments targeting amyloid beta (Aβ) plaques, disease-modifying therapies remain elusive. Early detection of mild cognitive impairment (MCI) patients at risk for AD conversion is crucial, especially with anti-Aβ therapy. While plasma biomarkers hold promise in differentiating AD from MCI, evidence on predicting cognitive decline is lacking. This study's objectives were to evaluate whether plasma protein biomarkers could predict both cognitive decline in non-demented individuals and the conversion to AD in patients with MCI. This study was conducted as part of the Korean Longitudinal Study on Cognitive Aging and Dementia (KLOSCAD), a prospective, community-based cohort. Participants were based on plasma biomarker availability and clinical diagnosis at baseline. The study included MCI (n = 50), MCI-to-AD (n = 21), and cognitively unimpaired (CU, n = 40) participants. Baseline plasma concentrations of six proteins-total tau (tTau), phosphorylated tau at residue 181 (pTau181), amyloid beta 42 (Aβ42), amyloid beta 40 (Aβ40), neurofilament light chain (NFL), and glial fibrillary acidic protein (GFAP)-along with three derivative ratios (pTau181/tTau, Aβ42/Aβ40, pTau181/Aβ42) were analyzed to predict cognitive decline over a six-year follow-up period. Baseline protein biomarkers were stratified into tertiles (low, intermediate, and high) and analyzed using a linear mixed model (LMM) to predict longitudinal cognitive changes. In addition, Kaplan-Meier analysis was performed to discern whether protein biomarkers could predict AD conversion in the MCI subgroup. This prospective cohort study revealed that plasma NFL may predict longitudinal declines in Mini-Mental State Examination (MMSE) scores. In participants categorized as amyloid positive, the NFL biomarker demonstrated predictive performance for both MMSE and total scores of the Korean version of the Consortium to Establish a Registry for Alzheimer's Disease Assessment Packet (CERAD-TS) longitudinally. Additionally, as a baseline predictor, GFAP exhibited a significant association with cross-sectional cognitive impairment in the CERAD-TS measure, particularly in amyloid positive participants. Kaplan-Meier curve analysis indicated predictive performance of NFL, GFAP, tTau, and Aβ42/Aβ40 on MCI-to-AD conversion. This study suggests that plasma GFAP in non-demented participants may reflect baseline cross-sectional CERAD-TS scores, a measure of global cognitive function. Conversely, plasma NFL may predict longitudinal decline in MMSE and CERAD-TS scores in participants categorized as amyloid positive. Kaplan-Meier curve analysis suggests that NFL, GFAP, tTau, and Aβ42/Aβ40 are potentially robust predictors of future AD conversion.

Potential mechanism of Taohong Siwu Decoction in preventing and treating postoperative delirium in intertrochanteric fracture patients based on retrospective analysis and network pharmacology

ObjectiveElderly patients with hip fractures are at a greater risk of developing postoperative delirium (POD), which significantly impacts their recovery and overall quality of life. Neuroinflammation is a pathogenic mechanism of POD. Taohong Siwu Decoction (THSWD), known for its ability to promote blood circulation and remove blood stasis, can effectively reduce inflammation in the nervous system. Therefore, the objective of this article is to provide a comprehensive summary of the clinical efficacy of THSWD in the prevention of POD. Additionally, it aims to investigate the underlying mechanism of THSWD in the prevention and treatment of POD using network pharmacology and molecular docking.MethodsWe conducted a retrospective analysis of patients with intertrochanteric fractures between January 2016 and October 2021. The patients were divided into two groups: the control and THSWD group. We performed a comparative analysis of hemoglobin (HB), albumin (ALB), C-reactive protein (CRP), blood urea nitrogen (BUN), and the blood urea nitrogen to creatinine ratio (BCR) on two different time points: the day before surgery (D0) and the third day after surgery (D3). Furthermore, we examined the incidence and duration of delirium, as well as the Harris Hip Score (HHS) at 3 months and 12 months post-surgery. Network pharmacology was employed to identify the primary targets and mechanisms of THSWD in the management of delirium. Molecular docking was employed to confirm the interaction between active ingredients and COX-2. Inflammatory cytokines, including cyclooxygenase-2 (COX-2), interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor- (TNF-α), were measured using the enzyme-linked immunosorbent assay (ELISA). The cognitive status of the patients was assessed using the Mini-Mental State Examination (MMSE) scoring system.ResultsRegardless of whether it is in D0 or D3, THSWD treatment can increase HB levels while decreasing BCR. In D3, the THSWD group demonstrated a significant reduction in the expression of CRP and BUN when compared to the control group. However, there were no significant differences in ABL levels, surgery duration, and blood loss between the two groups. Additionally, THSWD treatment requires fewer blood transfusions and can reduce the incidence and duration of POD. The results of the logistic analysis suggest that both CRP levels and BCR independently contribute to the risk of POD. Network pharmacology analysis indicates that THSWD has the potential to prevent and treat POD possibly through inflammatory pathways such as IL-17 signaling pathways and NF-kappa B signaling pathways. Molecular docking validated the interaction between the active ingredient of THSWD and COX-2. Furthermore, THSWD treatment can reduce the levels of COX-2, IL-1β, IL-6, TNF-α, BUN and CRP in the blood of patients with POD, increase HB levels, and enhance MMSE scores. The expression of COX-2 is positively associated with other inflammatory markers (IL-1β, IL-6, TNF-α, and CRP), and inversely associated with MMSE.ConclusionTHSWD has been found to have a preventive and therapeutic effect on POD in intertrochanteric fracture patients possibly through inflammatory pathways. This effect may be attributed to its ability to increase hemoglobin levels and reduce the levels of certain detrimental factors, such as blood urea nitrogen and inflammatory factors.

Tolerability and Efficacy of Bi-temporal Electroconvulsive Therapy in Elderly Patients with Severe Mental Illness

Background: Electroconvulsive therapy (ECT) has been an effective treatment option available for elderly patients with severe mental illness; however, there are concerns related to its tolerability. Unilateral ECT has fewer cognitive adverse effects compared to bilateral ECT while efficacy with bilateral ECT is better. Aim: To evaluate the tolerability and efficacy of Bi-temporal ECT in elderly patients (&gt;60 years) with severe mental illness in a general hospital set-up. Methodology: The study was a prospective, observational study conducted in SDM College of Medical Sciences and Hospital, Dharwad with a sample size of 15 elderly patients aged above 60 years with severe mental illness. Participants were screened for psychiatric symptoms with Mini-International Neuropsychiatric Interview and assessed for severity of symptoms with Hamilton Depression Rating Scale, Young Mania Rating Scale, and Positive and Negative Syndrome Scale. Cognitive functioning was assessed by Hindi Mental Status Examination Scale and effectiveness was assessed using global functioning by Global Assessment of Functioning (GAF) Scale. Assessment was done before giving ECT and 4 weeks at follow-up. The study period was from January 2019 to December 2019. Results and Conclusions: The median age of the elderly was 61 years. Majority (66.7%) were diagnosed with mood disorder and 33.3% of the patients were diagnosed with paranoid schizophrenia. Around 47% had comorbid hypertension and 33.3% had diabetes mellitus. All the patients in the study sample received thrice weekly bi-temporal ECT in the range of 2–8 with median of 5. Significant reduction in symptomatology was observed, on comparing the scores before and after ECT with improvement in overall functioning assessed by GAF Scale. There was no decline in cognitive functioning test, although there was an improvement in the Hindi version of mini mental status examination scores at 4 weeks after discharge. By the above observations, we concluded that the use of bi-temporal ECT in elderly patients with severe mental illness was found to be safe and effective in treating.

Combined Effect of Red Wine and Mocha Pot Coffee in Mild Vascular Cognitive Impairment

ObjectivesModerate daily mocha pot coffee intake has been associated with better mood and cognition in patients with mild vascular cognitive impairment (VCI). Similarly, moderate red wine consumption has shown protective effects on cognitive disorders, including Alzheimer's disease and vascular dementia. The aim of this study was to explore the synergistic relation between red wine and coffee intake on mood and cognitive status in mild VCI patients at risk for dementia. MethodsA total of 300 non-demented older patients with mild VCI were asked for coffee and red wine consumption and administered with the 17-items Hamilton Depression Rating Scale (HDRS), the Mini Mental State Examination (MMSE), and the Stroop Color-Word Interference Test (Stroop T), as well as the Activities of Daily Living (ADL) and the Instrumental ADL to measure their mood status, cognitive performance, and functional independence. Linear regression models were used to test the association between variables. ResultsModerate wine drinkers tended to show the best Stroop T score at any level of coffee consumption; conversely, heavy wine consumers performed worse at the Stroop T, especially in patients reporting high coffee intake. Moderate drinkers of both coffee and wine showed the lowest HDRS scores. Finally, a progressive increase in MMSE score was evident with increasing coffee consumption, which peaks when combined with a moderate wine consumption. ConclusionsDaily mocha pot coffee and red wine intake seem to be synergistically associated with global cognition, executive functioning, and mood status in patients with mild VCI; the association was not linear, resulting in a protective direction for moderate intake and detrimental for heavy consumption. Future studies are needed to further corroborate the present findings and the potential long-term protective effects of these dietary compounds over time.

Impact of thoracic paravertebral block and sufentanil on outcomes and postoperative cognitive dysfunction in thoracoscopic lung cancer surgery

BACKGROUND Postoperative pain management and cognitive function preservation are crucial for patients undergoing thoracoscopic surgery for lung cancer (LC). This is achieved using either a thoracic paravertebral block (TPVB) or sufentanil (SUF)-based multimodal analgesia. However, the efficacy and impact of their combined use on postoperative pain and postoperative cognitive dysfunction (POCD) remain unclear. AIM To explore the analgesic effect and the influence on POCD of TPVB combined with SUF-based multimodal analgesia in patients undergoing thoracoscopic radical resection for LC to help optimize postoperative pain management and improve patient outcomes. METHODS This retrospective analysis included 107 patients undergoing thoracoscopic radical resection for LC at The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital between May 2021 and January 2023. Patients receiving SUF-based multimodal analgesia (n = 50) and patients receiving TPVB + SUF-based multimodal analgesia (n = 57) were assigned to the control group and TPVB group, respectively. We compared the Ramsay Sedation Scale and visual analog scale (VAS) scores at rest and with cough between the two groups at 2, 12, and 24 h after surgery. Serum levels of epinephrine (E), angio-tensin II (Ang II), norepinephrine (NE), superoxide dismutase (SOD), vascular endothelial growth factor (VEGF), transforming growth factor-β1 (TGF-β1), tumor necrosis factor-α (TNF-α), and S-100 calcium-binding protein β (S-100β) were measured before and 24 h after surgery. The Mini-Mental State Examination (MMSE) was administered 1 day before surgery and at 3 and 5 days after surgery, and the occurrence of POCD was monitored for 5 days after surgery. Adverse reactions were also recorded. RESULTS There were no significant time point, between-group, and interaction effects in Ramsay sedation scores between the two groups (P &gt; 0.05). Significantly, there were notable time point effects, between-group differences, and interaction effects observed in VAS scores both at rest and with cough (P &lt; 0.05). The VAS scores at rest and with cough at 12 and 24 h after surgery were lower than those at 2 h after surgery and gradually decreased as postoperative time increased (P &lt; 0.05). The TPVB group had lower VAS scores than the control group at 2, 12, and 24 h after surgery (P &lt; 0.05). The MMSE scores at postoperative days 1 and 3 were markedly higher in the TPVB group than in the control group (P &lt; 0.05). The incidence of POCD was significantly lower in the TPVB group than in the control group within 5 days after surgery (P &lt; 0.05). Both groups had elevated serum E, Ang II, and NE and decreased serum SOD levels at 24 h after surgery compared with the preoperative levels, with better indices in the TPVB group (P &lt; 0.05). Marked elevations in serum levels of VEGF, TGF-β1, TNF-α, and S-100β were observed in both groups at 24 h after surgery, with lower levels in the TPVB group than in the control group (P &lt; 0.05). CONCLUSION TPVB combined with SUF-based multimodal analgesia further relieves pain in patients undergoing thoracoscopic radical surgery for LC, enhances analgesic effects, reduces postoperative stress response, and inhibits postoperative increases in serum VEGF, TGF-β1, TNF-α, and S-100β levels. This scheme also reduced POCD and had a high safety profile.

Altered Intrinsic Brain Activity in Ischemic Stroke Patients Assessed Using the Percent Amplitude of a Fluctuation Method.

Ischemic stroke is a vascular disease that may cause cognitive and behavioral abnormalities. This study aims to assess abnormal brain function in ischemic stroke patients using the percent amplitude of fluctuation (PerAF) method and further explore the feasibility of PerAF as an imaging biomarker for investigating ischemic stroke pathophysiology mechanisms. Sixteen ischemic stroke patients and 22 healthy controls (HCs) underwent resting state functional magnetic resonance imaging (rs-fMRI) scanning, and the resulting data were analyzed using PerAF. Then a correlation analysis was conducted between PerAF values and Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores. Finally, the abnormal PerAF values were extracted and defined as features for support vector machine (SVM) analysis. Compared with HCs, ischemic stroke patients showed decreased PerAF in the bilateral cuneus, left middle frontal gyrus, precuneus and right inferior temporal gyrus, and increased PerAF in the bilateral orbital part of middle frontal gyrus and right orbital part of superior frontal gyrus. Correlation analyses revealed that PerAF values in the left orbital part of middle frontal gyrus was negatively correlated with the MoCA scores. The SVM classification of the PerAF values achieved an area under the curve (AUC) of 0.98 and an accuracy of 94.74%. Abnormal brain function has been found among ischemic stroke patients, which may be correlated with visual impairment, attention deficits, and dysregulation of negative emotions following a stroke. Our findings may support the potential of PerAF as a sensitive biomarker for investigating the underlying mechanisms of ischemic stroke.

The Potential Neurological Impact of Intraoperative Hyponatremia Using Histidine-Tryptophan-Ketoglutarate Cardioplegia Infusion in Adult Cardiac Surgery.

Background and Objectives: The relationship between histidine-tryptophan-ketoglutarate (HTK)-induced hyponatremia and brain injury in adult cardiac surgery patients is unclear. This study analyzed postoperative neurological outcomes after intraoperative HTK cardioplegia infusion. Materials and Methods: A prospective cohort study was conducted on 60 adult patients who underwent cardiac surgery with cardiopulmonary bypass. Of these patients, 13 and 47 received HTK infusion and conventional hyperkalemic cardioplegia, respectively. The patients' baseline characteristics, intraoperative data, brain injury markers, Mini-Mental State Examination (MMSE) scores, and quantitative electroencephalography (qEEG) data were collected. Electrolyte changes during cardiopulmonary bypass, the degree of hyponatremia, and any associated brain insults were evaluated. Results: The HTK group presented with acute hyponatremia during cardiopulmonary bypass, which was intraoperatively corrected through ultrafiltration and normal saline administration. Postoperative sodium levels were higher in the HTK group than in the conventional cardioplegia group. The change in neuron-specific enolase levels after cardiopulmonary bypass was significantly higher in the HTK group (p = 0.043). The changes showed no significant differences using case-control matching. qEEG analysis revealed a significant increase in relative delta power in the HTK group on postoperative day (POD) 7 (p = 0.018); however, no significant changes were noted on POD 60. The MMSE scores were not significantly different between the two groups on POD 7 and POD 60. Conclusions: HTK-induced acute hyponatremia and rapid correction with normal saline during adult cardiac surgeries were associated with a potential short-term but not long-term neurological impact. Further studies are required to determine the necessity of correction for HTK-induced hyponatremia.

Parental History of Memory Impairment and β-Amyloid in Cognitively Unimpaired Older Adults

Studies have suggested that maternal history of late-onset Alzheimer disease, but not paternal, predisposes individuals to higher brain β-amyloid (Aβ) burden, reduced brain metabolism, and lower gray matter volumes. To characterize maternal vs paternal history of memory impairment in terms of brain Aβ-positron emission tomography (Aβ-PET) and baseline cognition among a large sample of cognitively unimpaired older adults. This cross-sectional study leveraged data from 4413 individuals who were screened for the Anti-Amyloid Treatment in Asymptomatic Alzheimer (A4) study, a randomized clinical trial conducted across 67 sites in the US, Australia, Canada, and Japan aimed at Alzheimer disease prevention. Data were collected between April 2014 and December 2017 and analyzed from December 2022 to June 2023. Participants were cognitively unimpaired adults (Clinical Dementia Rating = 0 and/or Mini-Mental State Examination score ≥25) between the ages of 65 and 85 years who underwent PET imaging to assess cortical Aβ levels for trial eligibility. A total of 4492 participants were screened, and 79 missing data were excluded. Demographic characteristics (eg, age, sex, education), apolipoprotein E genotyping, participant-reported parental history of memory impairment and parental age at symptom onset were collected as variables. Parental history was assessed in terms of continuous neocortical 18F-florbetapir Aβ-PET and the Preclinical Alzheimer Cognitive Composite. Of 4413 individuals (mean [SD] age, 71.27 [4.66] years, 2617 women [59.3%]), mean Aβ-PET was elevated in individuals with history of memory impairment in both parents (n = 455; mean [SD] standardized uptake value ratio [SUVR] = 1.12 [0.19]; Wilcoxon P = 1.1 × 10-5) and in those with only maternal history (n = 1772; mean [SD] SUVR = 1.10 [0.19]; Wilcoxon P = 2.70 × 10-5) compared with those with only paternal history (n = 632; mean [SD] SUVR = 1.08 [0.18]; Wilcoxon P = 1.1 × 10-5) or no family history (n = 1554; mean [SD] SUVR = 1.08 [0.19]; Wilcoxon P = 1.1 × 10-5). Paternal history of early-onset memory impairment (age <65 years) but not late-onset (age ≥65 years) was associated with elevated participant Aβ-PET (mean [SD] SUVR = 1.19 [0.21]; P = 3.00 × 10-6) in comparison with no paternal history (mean [SD] SUVR = 1.09 [0.19]) whereas maternal history was associated with elevated Aβ in both early-onset and late-onset groups. There was no association with cognition. In this study, maternal history (at any age) and paternal history of early-onset memory impairment were associated with Aβ burden among asymptomatic older individuals. Sex-specific parental history may help inform clinicians on likelihood of Aβ burden in offspring and help identify high-risk individuals at the earliest stages of disease for prevention.

Can weekend catch-up sleep decrease the risk of cognitive dysfunction in older adults?

This study investigated whether weekend catch-up sleep was related to a decreased risk of cognitive dysfunction in older Taiwanese adults by using self-reported diaries and objective accelerometer measurements. This cross-sectional study enrolled participants who were aged ≥ 65 years and had the capability to walk independently from a medical center in Taipei City, Taiwan, between September 2020 and December 2022. Self-reported sleep diaries and tri-axial accelerometers were used to record and measure sleep-related data for 7 consecutive nights. Weekend catch-up sleep was defined as the mean of weekend sleep time minus the mean of weekdays sleep time. Mini-Mental State Examination (MMSE) was evaluated the risk of cognitive dysfunction. The association between weekend catch-up sleep and the MMSE score was examined using a binary logistic regression model. A total of 215 older adults (53.0% female; 80.5 ± 7.1 years old; 11.6% at risk of cognitive dysfunction) were included. In the adjusted model (adjusted for sex, education level, moderate-to-vigorous physical activity and total accelerometer wear time), both the self-reported sleep diaries (odds ratio [OR] = 0.26, 95% confidence interval [CI] = 0.09-0.69, P = 0.007) and the accelerometer data (OR = 0.27, 95% CI = 0.10-0.70, P = 0.007) indicated that weekend catch-up sleep could decrease the risk of cognitive dysfunction by 73-74%. The study findings suggest that there is an association between weekend catch-up sleep and lower risk for cognitive decline. The causal relationship between weekend catch-up sleep and cognitive function in older adults should be further investigated in a study with longitudinal design.

A nomogram for predicting disability-free survival in older adults over 15 years: A population-based cohort study

BackgroundThis article aimed to develop and validate a simple-to-use nomogram to predict 15-year disability-free survival among older adults. MethodsA cohort of 1878 disability-free participants aged ≥60 was followed for 15 years. Participants were randomly divided into a training cohort for nomogram development (n = 1314 [70 %]) and validation cohort to confirm the model's performance (n = 564 [30 %]). Information on socio-demographic, lifestyle factors, the Life Satisfaction Index A (LSI-A), chronic diseases, and Mini-Mental State Examination (MMSE) score, and biomarkers were collected through interviews, clinical and neuropsychological examinations, and medical records. Disability-free survival was defined as survival in the absence of dementia and physical disability, and the composite endpoint is first occurrence of events of death, dementia and physical disability. We developed a nomogram summing the number of risk points corresponding to weighted covariates to predict disability-free survival. Validation of the nomogram using C statistic, calibration plots, and Kaplan-Meier curves. ResultsIn the multivariate-adjusted model, factors associated with composite end point were younger age, high MMSE (hazard ratio [HR], 0.93; [95 % CI, 0.87–0.99]), high LSI-A (0.78, [0.64–0.97]), non-smoking (0.74, [0.59–0.94]), engagement in physical leisure activity (0.62, [0.48–0.78]), and absence of chronic diseases (0.78, [0.66–0.91]). Incorporating these 6 factors, the nomogram achieved C-statistics of 0.78 (95 % CI, 0.75–0.81) and 0.77 (95 % CI, 0.74–0.80) in predicting disability-free survival in the training and validation cohorts, respectively, and had good calibration curves. ConclusionThe nomogram was able to predict long-term of disability-free survival and performed well on internal validation, and may be considered for use in effective surveillance, promote, management of clinical and public health ageing.

Comparative study of choline alfoscerate as a combination therapy with donepezil: A mixed double-blind randomized controlled and open-label observation trial.

Choline alfoscerate (alpha-glycerylphosphorylcholine) is a phospholipid that includes choline, which increases the release of acetylcholine. The ASCOMALVA trial, a combination of donepezil and choline alfoscerate, slowed cognitive decline in Alzheimer disease. This study aims to replicate the effect by combining donepezil with other nootropics currently used in South Korea. The 119 patients with cognitive decline who were eligible to use donepezil, with an mini-mental state examination (MMSE) score of 26 or less, were assigned to: donepezil alone (DO); donepezil and choline alfoscerate (DN); donepezil and acetyl-l-carnitine (DA); or donepezil and ginkgo biloba extract (DG). Cognitive evaluations such as MMSE, clinical dementia rating, Alzheimer disease assessment scale-cognitive subscale (ADAS-Cog), and Alzheimer disease assessment scale-noncognitive subscale were performed at the 12th and 24th weeks from the baseline time point. At the 12th week, the MMSE score increased 3.52% in the DN group, whereas it increased by 1.36% in the DO group. In the DA + DG group, it decreased by 2.17%. At the 24th week, the MMSE score showed an increase of 1.07% in the DO group and 1.61% in the DN group, but decreased by 5.71% in the DA + DG group. ADAS-Cog decreased by 0.9% in the DO group, while it improved by 13.9% in the DN group at the 12th week. At the 24th week, ADAS-Cog showed improvement in the DN group by 18.5%, whereas it improved by 9.4% in the DO group. Alzheimer disease assessment scale-noncognitive subscale also revealed better performance in the DN group than in the DO group at the 12th and 24th weeks. Choline alfoscerate exhibits additional cognitive improvement in both cognitive and noncognitive domains, supporting the findings of the ASCOMALVA trial.

Cognitive screening test for rehabilitation using spatiotemporal data extracted from a digital trail making test part-A

We investigated a newly developed digitized Trail Making Test using an iPad (iTMT) as a brief cognitive function screening test. We found that the iTMT part-A (iTMT-A) can estimate generalized cognitive function in rehabilitation inpatients examined using the Mini-Mental State Examination (MMSE). Forty-two hospitalized participants undergoing rehabilitation (rehab participants), 30 of whom had cerebral infarction/hemorrhage (stroke participants), performed the iTMT five times (first three times: iTMT-A; fourth: paper version of TMT-A; fifth: the inverse version of iTMT-A) and the MMSE once. Each iTMT-A trial's completion time was divided into the move and dwell times. A linear mixed model following post-hoc tests revealed that the completion time of the third and fourth iTMT-A was faster compared to that of the first iTMT-A, suggesting the presence of a learning effect. In the partial least squares (PLS) regression analysis, the coefficient of determination for estimating the MMSE score was increased by using the dwell and move times extracted from the repeated iTMT-A and the availability of TMT-B, even for subjects with low MMSE scores. These findings indicate that the dwell time of iTMT-A may be important for estimating cognitive function. The iTMT-A extracts significant factors temporally and spatially, and by incorporating the learning effect of repeated trials, it may be possible to screen cognitive and physical functions for rehabilitation patients.

Efficacy of a non-pharmaceutical multimodal intervention program in a group setting for patients with mild cognitive impairment: A single-arm interventional study with pre-post and external control analyses

AimThis study aimed to evaluate the efficacy of a non-pharmaceutical multimodal intervention program consisting of physical exercise, cognitive stimulation, and health education in a group setting to slow the progression of mild cognitive impairment (MCI). MethodsA single-arm interventional study was conducted on 27 patients with MCI. To evaluate the efficacy of the intervention program, a pre-post analysis was performed using EuroQol-5 Dimension (EQ-5D), Mini-Mental State Examination (MMSE), Cognitive Function Instrument (CFI), 5 Cog test, depression, and physical performance before and after the 8-month intervention. Additionally, propensity score and the semi-Bayes analyses were performed to compare the intervention program with standard medical care, using the external control patients’ data for MMSE scores. ResultsTwenty-four patients completed the intervention program. During the study period, although EQ-5D and MMSE scores remained unchanged (mean change 0.02 [95 % confidence interval (CI): −0.004, 0.04], 0.5 [-0.2, 1.3]), CFI and the subcategories of 5Cog (attention and reasoning) improved (mean change −1.23 [-2.24, −0.21], 4.3 [0.9, 7.7], 3.0 [0.4, 5.6]). In the additional analysis comparing changes in MMSE scores, patients who underwent the intervention program had less decline than the external control patients (mean change −1.7 [-2.1, −1.3]) with an observed mean difference of 2.25 [1.46, 3.03], and propensity score-adjusted difference of 2.26 [1.46, 3.05]. The semi-Bayesian approach also suggested that the intervention slowed the progression of MCI. ConclusionA non-pharmaceutical multimodal intervention program could contribute to slowing cognitive decline in patients with MCI.

Clinical efficacy of scalp electroacupuncture combined with rehabilitation training for aphasia after head injury and its effect on patients' language function and quality of life: An observational study.

To explore the clinical efficacy of scalp electroacupuncture combined with rehabilitation training for aphasia after head injury, and analyze its effect on patients' language function and quality of life. Our hospital randomly enrolled 100 aphasia patients caused by head injury treated from March 2020 to March 2022 as the experimental object and divided them into the control group and experimental group, with 50 cases in each group. The general rehabilitation training was performed to the control group and the scalp electroacupuncture combined with rehabilitation training was performed to the experimental group to compare their mini-mental state examination scores, communicative activities in daily living scores, aphasia battery of Chinese scores, quality of life scores, mental status scale in nonpsychiatric settings scores, National Institutes of Health Stroke Scale scores, effective rates, satisfaction of patients, and adverse reaction rates. In the between-group comparison, the patients in the experimental group had significantly higher mini-mental state examination scores, communicative activities in daily living scores, aphasia battery of Chinese scores, quality of life scores, effective rates, and satisfaction, and significantly lower mental status scale in nonpsychiatric settings scores, National Institutes of Health Stroke Scale scores and adverse reaction rates, which was statistically significant (P < .05 in all cases). The combination treatment of scalp electroacupuncture and rehabilitation training can effectively improve the language function and quality of life of patients with aphasia after head injury and remarkably enhance the treatment effect.

Predictors of Hospital Readmission, Institutionalization, and Mortality in Geriatric Rehabilitation Following Hospitalization According to Admission Reason.

Older adults following an inpatient geriatric rehabilitation (GR) program commonly experience adverse health outcomes such as hospital readmission, institutionalization, and mortality. Although several studies have explored factors related to these outcomes, the influence of admission reason on the predictive factors of adverse health outcomes in the rehabilitation process remains unclear. Therefore, this study aimed to identify predictive factors for adverse health outcomes in inpatients attending GR according to their admission reason. This retrospective study included patients with orthogeriatric (OG) conditions and patients with hospital-associated deconditioning (HAD) admitted to GR after an acute hospitalization between 2016 and 2020. Patients were evaluated by a comprehensive geriatric assessment at admission, including sociodemographic data, social resources, clinical data, cognitive, functional and nutritional status, and physical performance measurements. Adverse health outcomes were collected (hospital readmission, institutionalization, and mortality). Univariate analyses and multivariate backward binary logistic regressions were used to determine predictive factors. In this study, 290 patients were admitted for OG conditions, and 122 patients were admitted due to HAD. In patients with OG conditions, lower Mini-Mental State Examination (MMSE) predicted institutionalization and mortality. Lower Mini Nutritional Assessment-Short Form predicted institutionalization, whereas lower Barthel Index and lower Tinetti-Performance-Oriented Mobility Assessment scores were associated with higher mortality. In patients with HAD, higher age-adjusted comorbidity index predicted hospital readmission and mortality, and lower Short Physical Performance Battery scores predicted institutionalization and mortality. Finally, lower MMSE scores, worse values in Older Americans Resources and Services Scale and male gender were associated with a higher risk of institutionalization. Predictive factors for hospital readmission, institutionalization, and mortality in patients with OG conditions and HAD during GR were different. Some of those predictors, such as nutritional status and physical performance, are modifiable. Understanding predictive factors for adverse outcomes, and how these factors differ by admission diagnosis, improves our ability to identify patients most at risk. Early identification of these patients could assist with prevention efforts and lead to a reduction of negative outcomes.

Distinct effects of blood pressure parameters on Alzheimer’s and vascular markers in 1,952 Asian individuals without dementia

BackgroundRisk factors for cardiovascular disease, including elevated blood pressure, are known to increase risk of Alzheimer’s disease. There has been increasing awareness of the relationship between long-term blood pressure (BP) patterns and their effects on the brain. We aimed to investigate the association of repeated BP measurements with Alzheimer’s and vascular disease markers.MethodsWe recruited 1,952 participants without dementia between August 2015 and February 2022. During serial clinic visits, we assessed both systolic BP (SBP) and diastolic BP (DBP), and visit-to-visit BP variability (BPV) was quantified from repeated measurements. In order to investigate the relationship of mean SBP (or DBP) with Alzheimer’s and vascular markers and cognition, we performed multiple linear and logistic regression analyses after controlling for potential confounders (Model 1). Next, we investigated the relationship of with variation of SBP (or DBP) with the aforementioned variables by adding it into Model 1 (Model 2). In addition, mediation analyses were conducted to determine mediation effects of Alzheimer’s and vascular makers on the relationship between BP parameters and cognitive impairment.ResultsHigh Aβ uptake was associated with greater mean SBP (β = 1.049, 95% confidence interval 1.016–1.083). High vascular burden was positively associated with mean SBP (odds ratio = 1.293, 95% CI 1.015–1.647) and mean DBP (1.390, 1.098–1.757). High tau uptake was related to greater systolic BPV (0.094, 0.001–0.187) and diastolic BPV (0.096, 0.007–0.184). High Aβ uptake partially mediated the relationship between mean SBP and the Mini-Mental State Examination (MMSE) scores. Hippocampal atrophy mediated the relationship between diastolic BPV and MMSE scores.ConclusionsEach BP parameter affects Alzheimer’s and vascular disease markers differently, which in turn leads to cognitive impairment. Therefore, it is necessary to appropriately control specific BP parameters to prevent the development of dementia. Furthermore, a better understanding of pathways from specific BP parameters to cognitive impairments might enable us to select the managements targeting the specific BP parameters to prevent dementia effectively.