Cognitive Subscale Research Articles

Relation of prenatal and postnatal PM2.5 exposure with cognitive and motor function among preschool-aged children

The literature informing susceptible periods of exposure on children's neurodevelopment is limited. We evaluated the impacts of pre- and postnatal fine particulate matter (PM2.5) exposure on children's cognitive and motor function among 1303 mother-child pairs in the Spanish INMA (Environment and Childhood) Study. Random forest models with temporal back extrapolation were used to estimate daily residential PM2.5 exposures that we averaged across 1-week lags during the prenatal period and 4-week lags during the postnatal period. The McCarthy Scales of Children's Abilities (MSCA) were administered around 5 years to assess general cognitive index (GCI) and several subscales (verbal, perceptual-performance, memory, fine motor, gross motor). We applied distributed lag nonlinear models within the Bayesian hierarchical framework to explore periods of susceptibility to PM2.5 on each MSCA outcome. Effect estimates were calculated per 5 μg/m3 increase in PM2.5 and aggregated across adjacent statistically significant lags using cumulative β (βcum) and 95% Credible Intervals (95%CrI). We evaluated interactions between PM2.5 with fetal growth and child sex. We did not observe associations of PM2.5 exposure with lower GCI scores. We found a period of susceptibility to PM2.5 on fine motor scores in gestational weeks 1–9 (βcum = −2.55, 95%CrI = −3.53,-1.56) and on gross motor scores in weeks 7–17 (βcum = −2.27,95%CrI = −3.43,-1.11) though the individual lags for the latter were only borderline statistically significant. Exposure in gestational week 17 was weakly associated with verbal scores (βcum = −0.17, 95%CrI = −0.26,-0.09). In the postnatal period (from age 0.5–1.2 years), we observed a window of susceptibility to PM2.5 on lower perceptual-performance (β = −2.42, 95%CrI = −3.37,-1.46). Unexpected protective associations were observed for several outcomes with exposures in the later postnatal period. We observed no evidence of differences in susceptible periods by fetal growth or child sex. Preschool-aged children's motor function may be particularly susceptible to PM2.5 exposures experienced in utero whereas the first year of life was identified as a period of susceptibility to PM2.5 for children's perceptual-performance.

Deep brain stimulation of the nucleus basalis of Meynert in severe Alzheimer’s disease

Background Alzheimer's disease (AD) is increasingly prevalent, leading to severe cognitive decline and a diminished quality of life for patients. Nucleus basalis of Meynert deep brain stimulation (NBM-DBS) is a potential treatment approach. Objective This study aims to assess the efficacy and safety of NBM-DBS for AD patients. Methods We conducted a clinical study involving 6 patients with severe AD who received NBM-DBS. The treatment's safety and efficacy were evaluated using cognitive function tests (Mini-Mental State Examination, Montreal Cognitive Assessment, Alzheimer's Disease Rating Scale- cognitive subscale, Clinical Dementia Rating) and assessments of neuropsychiatric symptoms and sleep disorders (Functional Activity Questionnaire, Functional Independence Measure, Zarit Burden Interview, Hamilton Anxiety Rating Scale, Hamilton Depression Rating Scale, Neuropsychiatric Inventory, Pittsburgh Sleep Quality Index). Results NBM-DBS was safe, with no severe adverse events. It improved cognitive functions and self-care abilities without altering the disease's progression. Notably, NBM-DBS significantly alleviated neuropsychiatric symptoms and sleep disturbances. Conclusions NBM-DBS could be a promising therapeutic approach for severe AD, particularly for managing neuropsychiatric symptoms and sleep disorders. Further research is warranted to confirm these preliminary findings.

Multi-center open comparative randomized study of efficacy and safety of Akatinol Memantine 20 mg (single-doses) vs Akatinol Memantine 10 mg (double-doses) in patients with vascular dementia

Evaluation of the efficacy and safety of the drug Acatinol Memantine, 20 mg (once daily) in comparison with the drug Acatinol Memantine, 10 mg (twice daily) in patients with moderate to moderate severe vascular dementia. The study included 130 patients aged 50-85 years of both sexes with instrumentally and clinically confirmed vascular dementia. The patients were randomized into 2 groups. Group I consisted of 65 patients receiving Akatinol Memantine, 20 mg once daily, group II - 65 patients receiving Akatinol Memantine, 10 mg twice daily for 24 weeks. Clinical, parametric and statistical research methods were used. The Alzheimer's disease assessment scale, the cognitive subscale (ADAS-cog), the short mental Status Assessment Scale (MMSE) and the general clinical impression scale for patients condition and illness severity (CGI-C and CGI-S) and the Hamilton Depression Rating scale (HAM-D) were used. Adverse events were collected and analyzed. At week 24, both groups showed statistically significant positive change in ADAS-cog total score: in group I the total score was 27.2±8.76 points (absolute difference from baseline 3.5 points; p<0.01), and in group II - 26.1±7.86 points (absolute difference from baseline 2.5 points; p<0.01) with no statistically significant differences between groups. Evaluation of secondary efficacy criteria (change in ADAS-cog total score at week 12 and MMSE at weeks 4, 12, and 24) also revealed statistically significant benefit in both groups compared to baseline with no significant differences between groups. Statistically significant improvement was noticed on CGI-S and CGI-C scales in both groups. Akatinol Memantine was safe and well tolerated in both groups. The study showed no lesser efficacy and safety of Akatinol Memantine, 20 mg (once daily) compared to Akatinol Memantine, 10 mg (twice daily) in patients with moderate and moderately severe vascular dementia.

Relationship Between the Decision-Making Balance Regarding Organ Donation and Level of Empathy.

In Turkey, the rate of organ donations has not reached the desired level. Although the vital importance of organ transplantation is known, the low participation in organ donation is an issue that needs to be examined meticulously. Organ donation decisions can be affected by demographic factors, such as family, personality traits, and religion and by psychological factors, such as attitude, intention, and sacrifice. For this reason, it is important to find the reasons that prevent people from being a donor and to develop intervention methods for them. In this context, we aimed to evaluate the relationship between the balance of decision-making regarding organ donation and the level of empathy. A total of 638 adults (mean age of 25.32 ± 9.95 years; n = 468 female participants and n = 170 male participants) voluntarily participated in the study. We used the Organ Donation Decisional Balance Survey to measure basic information on participants' personal valuations on the importance of positive and negative aspects of donor decisions. We used the Empathy Quotient scale to determine the empathy level of participants. We determined the relationship between variables using Pearson correlation analysis. Organ donation balance had positive correlations with measures of cognitive empathy subscale (r = 0.115; P < .01), emotional reactivity subscale (r = 0.117; P < .01), and social skills subscale (r = 0.084; P < .05). We found a positive relationship between empathy and the individual decision-making balance on donation; therefore, empathy development and altruism may affect organ donation decisions.

Shortening the Alzheimer's disease assessment scale cognitive subscale.

A short yet reliable cognitive measure is needed that separates treatment and placebo for treatment trials for Alzheimer's disease. Hence, we aimed to shorten the Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAS-Cog) and test its use as an efficacy measure. Secondary data analysis of participant-level data from five pivotal clinical trials of donepezil compared with placebo for Alzheimer's disease (N=2,198). Across all five trials, cognition was appraised using the original 11-item ADAS-Cog. Statistical analysis consisted of sample characterization, item response theory (IRT) to identify an ADAS-Cog short version, and mixed models for repeated-measures analysis to examine the effect sizes of ADAS-Cog change on the original and short versions in the placebo versus donepezil groups. Based on IRT, a short ADAS-Cog was developed with seven items and two response options. The original and short ADAS-Cog correlated at baseline and at weeks 12 and 24 at 0.7. Effect sizes based on mixed modeling showed that the short and original ADAS-Cog separated placebo and donepezil comparably (ADAS-Cog original ES=0.33, 95% CI=0.29, 0.40, ADAS-Cog short ES=0.25, 95% CI =0.23, 0.34). IRT identified a short ADAS-cog version that separated donepezil and placebo, suggesting its clinical potential for assessment and treatment monitoring.

The dual effect of vagus nerve stimulation in pediatric patients with drug-resistant epilepsy: Is there more than seizure control?

This is a retrospective and comparative pilot study to investigate the role of vagus nerve stimulation (VNS) in improving cognitive functions in the pediatric age group with drug resistant epilepsy (DRE). It was conducted from January 2018 to February 2023. Children between the ages of 4 and 18 years were divided into two groups, the “VNS group” and the “best medical treatment (BMT) group”. Follow up period was 12 months. Demographic, clinical, etiological and investigational data were recorded. Cognitive assessment using the Modified Mini-Mental State Examination for children (MMSE) was recorded at baseline and 12 months later for each group. 76.4 % of patients were classified as epilepsy secondary to cerebral palsy. 75 % of patients showed ≥ 50 % seizure frequency reduction among the VNS group as compared to 12.5 % in the BMT group. None of both groups achieved seizure freedom. At 12 months, both BMT and VNS groups showed statistically significantly improved overall cognitive score from baseline records (p = 0.027) and (p = 0.012), respectively, with a significantly higher improvement in VNS group. Also, statistical sub-analysis of cognitive subscales in cerebral palsy patients in both groups was conducted and revealed a significant improvement (p = 0.02) in the VNS group. We concluded that there is a potential role of VNS in improving cognitive functions which was shown by using a cost-effective screening tool. A significant effect was observed specially in cerebral palsy patients. This is very beneficial in limited-resources countries since VNS has good safety profile, high seizure control, and added value to cognitive functions.

Efficacy and safety of chinese herbal medicines combined with chemical drugs for alzheimer's disease: A systematic review and meta-analysis

Objective: To evaluate the efficacy and safety of Chinese herbal medicines (CHMs) combined with chemical drugs for the treatment of Alzheimer's disease (AD). Materials and Methods: Databases were searched to retrieve randomized controlled trials (RCTs) of CHMs combined with tacrine, galantamine, rivastigmine, donepezil, or memantine, following strict inclusion and exclusion criteria. Only research papers published in English, Chinese, and Japanese were considered. The primary outcome was the mini-mental state examination (MMSE) score and the secondary outcomes were AD assessment scale cognitive subscale (ADAS-Cog) score and safety evaluation. Meta-analysis was carried out using RevMan 5.3 and subgroup analysis was conducted to identify the sources of heterogeneity. Results: A total of 15 RCTs with 1386 participants were included in this study. Only donepezil was used in the retrieved literature. Meta-analyses showed that the combination of CHMs with donepezil led to significant improvement in the MMSE score (Z = 9.45; P &lt; 0.00001; weighted mean difference [WMD] =2.68, 95% confidence interval [CI]: 2.12–3.24) and a significant decrease in the ADAS-Cog score (Z = 5.53; P &lt; 0.00001; WMD = −3.79; 95% CI: −5.13–−2.44). Safety evaluation demonstrated that these combination treatments relieved adverse events such as insomnia (risk ratio [RR] =0.20, 95% CI: 0.06–0.68; P = 0.01) and hive (RR = 0.10; 95% CI: 0.01–0.73; P = 0.02). Conclusions: The combination of CHMs with a chemical drug like donepezil led to significant improvements in patient cognition as well as a better safety profile when compared to the application of a chemical drug alone.

Factors related to the attitudes towards the older adults and emphatic skills of gerontology students

Aim: In this study, we aimed to determine the factors related to the attitudes and empathic skill levels of gerontology students towards the older adults. Methods: 167 Gerontology students participated in our study. Data were collected by Google online survey method using personal information form, Kogan's Attitude towards Elderly Scale and Basic Empathy Scale. Results: Mean age of the students is 21.41 ± 2 year, 80% were female. A statistically significant difference was found between the students' grade level, their mother's education level, whether they lived with an older adult at any time in their lives, the duration of living with an older adult and the total score of the attitude towards the elderly scale (p &lt; 0.001, 0.002, 0.017, 0.044, respectively). There was a statistically significant difference between gender, mother's education level, the place where they lived for the longest time and the positive attitude score towards the elderly (p = 0.008, 0.005, 0.019, respectively). There was a statistically significant difference between the students' grade level, number of siblings, whether they lived with an older adult at any time in their lives and the negative attitude score towards the elderly (p&lt;0.001, 0.016, 0.028, respectively). A statistically significant difference was found between gender, mother's education level and the total score of the basic empathy scale (p&lt;0.001, 0.005, respectively), emotional subscale (p&lt;0.001, 0.041, respectively) and cognitive subscale scores (p = 0.007, 0.005, respectively). The mean Attitudes Towards Elderly Scale Total Score, Positive Attitude Sub-scale Score and Negative Attitude Sub-scale Score of the students were 156.52 ± 17.54, 72.59 ± 11.02 and 83.93 ± 11.89, respectively. The mean scores of Basic Empathy Scale Total Score, Cognitive Sub-scale Score and Emotional Sub-scale Score were 78.05 ± 10.19, 37.04 ± 4.94 and 41.02 ± 7.13, respectively. Conclusions: In our study, it was determined that the gerontology department students had high attitudes and empathic skills towards the older adults.

The Cortical Silent Period and Its Association with Fatigue in Multiple Sclerosis: The Need for Standardized Data Collection.

The cortical silent period (CSP), assessed with transcranial magnetic stimulation (TMS), provides insights into motor cortex excitability. Alterations in the CSP have been observed in multiple sclerosis (MS), although a comparison of the sometimes contradictory results is difficult due to methodological differences. The aim of this study is to provide a more profound neurophysiological understanding of fatigue's pathophysiology and its relationship to the CSP. Twenty-three patients with MS, along with a matched control group, underwent comprehensive CSP measurements at four intensities (125, 150, 175, and 200% resting motor threshold), while their fatigue levels were assessed using the Fatigue Scale for Motor and Cognitive Functions (FSMC) and its motor and cognitive subscore. MS patients exhibited a significantly increased CSP duration compared to controls (p = 0.02), but CSP duration was not associated with the total FSMC, or the motor or cognitive subscore. Our data suggest a systematic difference in MS patients compared to healthy controls in the CSP but no association with fatigue when measured with the FSMC. Based on these results, and considering the heterogeneous literature in the field, our study highlights the need for a more standardized approach to neurophysiological data collection and validation. This standardization is crucial for exploring the link between TMS and clinical impairments in diseases like MS.

Do physical fitness and cognitive function mediate the relationship between basic activities of daily living and quality of life in older adults with dementia?

PurposeIndependence in activities of daily living (ADLs) is associated with quality of life (QoL) in individuals with dementia. However, the contribution of physical and cognitive functions to this relationship needs further examination. This study aims to examine the mediating effect of physical fitness and cognitive function in the relationship between independence in basic ADLs and QoL among older adults with dementia.MethodsThis cross-sectional study included 107 older adults with dementia (74.8% women; age 78.21 ± 7.70 years). Independence in basic ADL and QoL were evaluated using the Barthel Index (BI) and QoL- Alzheimer’s Disease Scale, respectively. The Alzheimer’s Disease Assessment Scale–Cognitive Subscale and the Mini-Mental State Examination were applied to assess cognitive function. Physical fitness was evaluated using the 30-s chair stand, 2-min step and the Timed-Up and Go tests. A structural equation modelling (SEM) with bootstrapping estimation was conducted to determine the relationship between all variables.ResultsIndependence in basic ADL positively affected QoL and this association was mediated by physical fitness (β = 0.242, p = 0.011). No statistically significant results were observed when testing cognitive function as a mediator between BI and QoL (β = 0.009, p = 0.345).ConclusionsPhysical fitness (i.e., lower body strength, aerobic capacity, and mobility) plays a role in the relationship between basic ADL independence and QoL of older adults with dementia, reinforcing the need to improve and monitor these parameters throughout the disease progression. Future longitudinal studies should explore the temporal relationship between physical and cognitive function and its contribution to basic ADL independence and QoL.

NeuroEPO plus (NeuralCIM®) in mild-to-moderate Alzheimer’s clinical syndrome: the ATHENEA randomized clinical trial

BackgroundNeuroEPO plus is a recombinant human erythropoietin without erythropoietic activity and shorter plasma half-life due to its low sialic acid content. NeuroEPO plus prevents oxidative damage, neuroinflammation, apoptosis and cognitive deficit in an Alzheimer’s disease (AD) models. The aim of this study was to assess efficacy and safety of neuroEPO plus.MethodsThis was a double-blind, randomized, placebo-controlled, phase 2–3 trial involving participants ≥ 50 years of age with mild-to-moderate AD clinical syndrome. Participants were randomized in a 1:1:1 ratio to receive 0.5 or 1.0 mg of neuroEPO plus or placebo intranasally 3 times/week for 48 weeks. The primary outcome was change in the 11-item cognitive subscale of the AD Assessment Scale (ADAS-Cog11) score from baseline to 48 weeks (range, 0 to 70; higher scores indicate greater impairment). Secondary outcomes included CIBIC+, GDS, MoCA, NPI, Activities of Daily Living Scales, cerebral perfusion, and hippocampal volume.ResultsA total of 174 participants were enrolled and 170 were treated (57 in neuroEPO plus 0.5 mg, 56 in neuroEPO plus 1.0 mg and 57 in placebo group). Mean age, 74.0 years; 121 (71.2%) women and 85% completed the trial. The median change in ADAS-Cog11 score at 48 weeks was −3.0 (95% CI, −4.3 to −1.7) in the 0.5 mg neuroEPO plus group, −4.0 (95% CI, −5.9 to −2.1) in the 1.0 mg neuroEPO plus group and 4.0 (95% CI, 1.9 to 6.1) in the placebo group. The difference of neuroEPO plus 0.5 mg vs. placebo was 7.0 points (95% CI, 4.5–9.5) P = 0.000 and between the neuroEPO plus 1.0 mg vs. placebo was 8.0 points (95% CI, 5.2–10.8) P = 0.000. NeuroEPO plus treatment induced a statistically significant improvement in some of clinical secondary outcomes vs. placebo including CIBIC+, GDS, MoCA, NPI, and the brain perfusion.ConclusionsAmong participants with mild-moderate Alzheimer’s disease clinical syndrome, neuroEPO plus improved the cognitive evaluation at 48 weeks, with a very good safety profile. Larger trials are warranted to determine the efficacy and safety of neuroEPO plus in Alzheimer’s disease.Trial registrationhttps://rpcec.sld.cu Identifier: RPCEC00000232.

The effect of black mulberry (Morus nigra) consumption on cognition in patients with mild-to-moderate Alzheimer's dementia: A pilot feasibility study

The purpose of this study was to test the feasibility and the possible effects of black mulberry on cognitive functions in Alzheimer's disease (AD). A total of 39 participants aged 65+ with mild-to-moderate AD were involved and 20 subjects were administered 20g of black mulberry concentrate daily for 12 weeks (intervention group), while 19 received no intervention (control group). Cognitive assessment utilized with Mini-Mental State Examination (MMSE) and AD Assessment Scale–Cognitive Subscale (ADAS-Cog) tests; Geriatric Depression Scale (GDS-15) used for depression screening. At the end of the study, although MMSE scores decreased (p = 0.003) and GDS-15 scores increased (p = 0.034) in control group, there was no change in intervention group. On the contrary, ADAS-Cog scores decreased in intervention group (p = 0.002) while the control group showed no improvement. This study showed that treatment of black mulberry (Morus nigra) for 12 weeks may slightly improve cognitive function in patients with AD.

A short‐hybrid scale for detecting anosognosia from the prodromal stage of Alzheimer’s disease

AbstractBackgroundWhile not originally developed for this purpose, evidence suggests that the Healthy Aging Brain Care Monitor questionnaire (HABC‐M; Monahan et al, 2012, 2014) may be a valuable instrument for assessing unawareness of cognitive decline (i.e., anosognosia) from preclinical stages of Alzheimer’s disease (AD) (Cacciamani et al, 2017). This is relevant because anosognosia may delay AD diagnosis and therapeutic interventions, with adverse consequences for patients and caregivers. However, several open questions remain: What is the actual effectiveness of this instrument across the AD spectrum? How do the cognitive, functional, and psychological subscales of the HABC‐M differ in their sensitivity to anosognosia in AD? Does the caregiver burden subscale provide additional information about AD patient’s anosognosia? The present study aimed to address these specific questions.MethodsThe HABC‐M was administered to 60 participants (30 AD patients and 30 healthy controls) and their partners (caregivers/informants). A measure of self‐awareness was then estimated by computing the discrepancy scores between the participants and their partners for the different subscales of HABC‐M (with the exception of the caregiver burden subscale, which is a caregiver‐exclusive questionnaire). To evaluate whether these measures can discriminate between patients at different stages of AD and controls, we fit linear models adjusted for age, sex, and education, and computed receiver operating characteristic curves.ResultsAll HABC‐M discrepancy scores, as well as the caregiver burden score, were able to discriminate controls from patients in distinct AD stages. For best performance, the area‐under‐curve for the HABC‐M cognitive subscale discriminated prodromal AD versus controls with a value 0.88 [95% CI: 0.78;0.97]. Adding the caregiver burden score raised it to 0.94 [0.86;0.99].ConclusionThe HABC‐M cognitive subscale (six items) can detect anosognosia from the earliest stages of AD. Separately, the caregiver burden subscale (four items) may corroborate the suspicion of anosognosia. A short‐hybrid scale combining these 10 items, instead of the 31 items of the total HABC‐M questionnaire, could provide a practical and efficient instrument for detection of anosognosia in the clinical setting. Importantly, such an instrument could further contribute to a timely AD diagnosis.

Precuneus magnetic stimulation for Alzheimer’s disease: a novel TMS‐EEG based peronsalized therapeutic strategy

AbstractBackgroundRepetitive transcranial magnetic stimulation (rTMS) may improve cognition in patients with Alzheimer’s disease (AD). rTMS therapy is currently limited by the relative short duration and the uncertainty on the most appropriate brain target area. AD patients primarily show alterations of the default mode network (DMN), a brain functional network for which the precuneus (PC) is a key node.MethodWe hypothesized that a long‐term 6 month course of rTMS applied over the precuneus could modify cognitive functions in patients with mild‐to‐moderate AD, by restoring cortical activity in the target network. To test this hypothesis we performed a randomized, double‐blind, sham‐controlled, phase II, 24‐weeks trial (NCT03778151). The primary outcome measure was change from baseline to week 24 of the Clinical Dementia Rating Scale–Sum of Boxes (CDR‐SOB). Secondary outcomes included score changes in the Alzheimer’s Disease Assessment Scale– Cognitive Subscale (ADAS‐Cog)11, Mini Mental State Examination (MMSE) and Alzheimer’s Disease Cooperative Study–Activities of Daily Living scale (ADCS‐ADL).Personalization of treatment and monitoring of cortical activity changes were refined by combining TMS and electroencephalography (TMS‐EEG).ResultWe found that AD patients treated with PC‐rTMS showed almost no decline in the CDR‐SB score, showing a clear advantage in terms of cognitive functions and functional abilities as compared to the sham group. rTMS induced in parallel remarkable changes in cortical activity, as demonstrated by TMS‐EEG recordings.Conclusion24 weeks of PC‐ rTMS may slow down cognitive and functional decline in AD patients by enhancing brain plasticity. Non‐invasive brain stimulation of the DMN could represent a novel therapeutic approach in AD patients.

Impact of sex and ApoE4 on the longitudinal association of plasma ptau‐181 and NFL with cognitive decline in non‐demented older adults

AbstractBackgroundAPOE4 is a strong genetic risk factor for Alzheimer’s disease (AD). Sex‐dependent differences has been shown in AD pathophysiology and clinical course. Here, we aim to assess the association between longitudinal changes in ptau‐181 and neurofilament light protein (NfL) and concurrent changes in cognitive measures in non‐demented individuals and to evaluate if this association is impacted by sex and ApoE4 status.MethodParticipants (N = 738) were non‐demented (cognitively unimpaired or mild cognitive impairment) older adults from the Alzheimer’s Disease Neuroimaging Initiative (ADNI, N = 738) with up to 4ys of longitudinal data. Linear Mixed Effects (LME) models were used to study the effect of ptau‐181 and NFL on cognition as measured by the cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS‐cog11; Range 0‐70) and Clinical Dementia Rating, sum of boxes (CDR‐SB). Sex by time and APOE4 by time interactions were assessed in the models for the entire sample. Analyses was repeated after separately stratifying sample by sex and APOE4.ResultAt baseline, both ADAS‐11 and CDRSB values correlated with plasma p‐Tau181 and NfL measures (Table 1). The longitudinal change in plasma p‐Tau181 correlated only with baseline CDR‐SB while that of NfL correlated with baseline ADAS‐11. The APOE4*time interaction, but not sex‐time interaction, were significant in LME models of both p‐Tau181 and NFL (Table 2). When stratified by sex, in females longitudinal increase in p‐Tau181 was associated with cognitive decline measured by both ADAS‐11 and CDR‐SB. In males, longitudinal increase in p‐Tau181 was associated with increase in ADAS‐11 scores and NfL was associated with cognitive decline on both outcomes. When stratified by APOE4 status, longitudinal changes in plasma biomarkers were only associated with cognitive decline in the APOE4+ subsample.ConclusionPlasma NfL and pTau increase during early AD and can be used to monitor disease progression. The relationship between increase in plasma ptau‐181 and NFL levels and worsening of cognition is affected by APOE4 status.

Magnetic Resonance Spectroscopy metabolites as biomarkers of Alzheimer’s Disease

AbstractBackgroundMagnetic resonance spectroscopy (MRS) is a non‐invasive method of evaluating metabolite levels in the cerebral cortex. Measurable metabolites can provide markers of neuronal damage, glial activation and, neurotransmission, pathological features of Alzheimer’s disease. Here we sought to establish the effectiveness of several metabolites as biomarkers for Alzheimer’s disease.Method198 participants with a single‐voxel 1H MRS scan were enrolled (n = 170 participants living with Alzheimer’s disease, n = 28 healthy controls). All participants underwent 3‐tesla magnetic resonance imaging and cognitive assessment with the Alzheimer’s Disease Assessment Scale–Cognitive Subscale (ADAS‐cog). An experienced radiographer placed an 8cm3 voxel within the posterior cingulate cortex for single‐voxel 1H MRS acquisition. Scans were then processed to evaluate levels of N‐acetylaspartate, myo‐inositol, choline, and glutamate. Creatine peak was additionally evaluated as a reference. N‐acetylaspartate/creatine, myo‐inositol /creatine, choline/creatine ratios and glutamate were compared between Alzheimer’s participants and controls to calculate the effect size. Correlations were then performed between metabolite ratios and ADAS‐cog scores.ResultN‐acetylaspartate/creatine effectively distinguished between Alzheimer’s patients and healthy controls (Cohens D = 0.83) with a lowered ratio in Alzheimer’s participants. Elevated glutamate signal and myo‐inositol/creatine ratios were also displayed in Alzheimer’s patients (Cohens D = 0.62 and 0.69, respectively). Choline/creatine ratio displayed no significant difference between groups (Cohens D = 0.26). Lower N‐acetylaspartate /creatine and glutamate correlated with higher ADAS‐cog scores (r = ‐0.29, p &lt; 0.001, CIs: ‐0.42 to ‐0.14 and r = ‐0.30, p &lt; 0.001, CIs: ‐0.44 to ‐0.16, respectively). Myo‐inositol and choline failed to correlate with cognitive impairment.ConclusionN‐acetylaspartate, a signature of neuronal damage, is an effective biomarker of Alzheimer’s disease and associated cognitive decline. Enhanced glial activity, measured with myo‐inositol, was shown in Alzheimer’s disease, suggesting that glial‐reactivity markers deserve consideration in the diagnosis of Alzheimer’s disease. Glutamate demonstrated the strongest association with cognitive impairment, despite showing a smaller effect size than N‐acetylaspartate and myo‐inositol in distinguishing between Alzheimer’s patients and controls. Together we establish MRS is a useful, non‐invasive biomarker of several pathological processes involved in the development of Alzheimer’s. Evaluation of N‐acetylaspartate, glutamate, and myo‐inositol may aid in the diagnosis of neurodegenerative disease, detecting markers undetectable by conventional MRI methodology.

Odor Identification Moderates Relationship Between Cognitive Training and Cognitive Decline

AbstractBackgroundOlfactory deficits have been shown to predict cognitive decline. Recent findings suggest that computerized cognitive training may reduce the risk of cognitive decline and dementia. However, the impact of olfaction deficits on cognitive training outcomes is unclear. In this study, we investigate how lower odor identification may moderate the relationship between treatment assignment (cognitive games versus crossword puzzles) and cognitive outcomes in older adults diagnosed with mild cognitive impairment (MCI).MethodData were drawn from the Cognitive Training and Neuroplasticity in Mild Cognitive Impairment (COG‐IT) Trial (NCT03205709). In this two‐site, single‐blinded, 78‐week trial, participants with MCI — stratified by age, severity (early/late MCI), and site — were randomly assigned to 12 weeks of intensive, home‐based, Computerized Cognitive Training (CCT) or computerized Crossword Puzzle Training (CPT), followed by six booster sessions. 106 patients received neuropsychological and olfactory assessments through the 11‐item Alzheimer’s Disease Assessment Scale–Cognitive Subscale (ADAS‐Cog) and the 40‐item University of Pennsylvania Smell Identification Test (UPSIT). In linear mixed‐model analyses, the effect of baseline UPSIT score on change in the ADAS‐Cog score from baseline over 78 weeks by treatment group, adjusted for age and baseline ADAS‐Cog, was assessed.ResultAmong 106 older adults (n = 50 [games]; n = 56 [crosswords]), higher baseline UPSIT scores predicted improved ADAS‐Cog performance at week 78 for all patients randomized to CPT (beta coefficient, 0.15, 95% confidence interval [CI], 0.02 to 0.27; P = 0.02). Greater baseline UPSIT score predicted improved ADAS‐Cog performance at weeks 12, 52, and 78 for early MCI patients randomized to CPT (Week 12: beta coef. 0.26, 95% CI 0.09 to 0.43; Week 52: beta coef. 0.23, 95% CI 0.05 to 0.40; Week 78: beta coef. 0.22, 95% CI 0.05 to 0.39). This was not shown in early MCI patients randomized to CCT. Higher baseline UPSIT predicted significant improvement in ADAS‐Cog for late MCI patients randomized to CCT at week 78 (beta coefficient, 0.24, 95% CI 0.05 to 0.42; P = 0.01).ConclusionOur results are consistent with literature, suggesting that impaired olfaction moderates memory decline. Our preliminary results show that individuals with less impaired olfaction may experience greater cognitive improvement following cognitive training.

Predictive Value of CSF Inflammatory Biomarkers in Alzheimer’s disease

AbstractBackgroundA growing body of evidence suggests that neuroinflammation contributes actively to pathophysiology Alzheimer’s disease (AD) and promotes AD progression. The predictive value of neuroinflammatory biomarkers for disease‐staging or estimating disease progression is not well understood. In this study, we investigate the diagnostic (i.e., differentiating clinical stages of disease) and prognostic (estimating probability of cognitive decline) ability of inflammatory biomarkers in combination with conventional AD biomarkers.MethodsWe included 242 participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) who had CSF biomarkers of Aβ, tau, and inflammation. Outcome of interest was clinically meaningful cognitive decline (CMCD) as defined by an increase of ≥4 on the Alzheimer’s Disease Assessment Scale Cognitive Subscore 11 (ADAS‐11, scores 0‐70, higher scores indicate worse cognition). Predictor variables were categorized as demographics (D; age, sex, and education), genetic information such as APOE4 status (G), inflammatory biomarkers (I; see Table 1 for details), and cerebrospinal fluid (CSF) biomarkers of β‐amyloid (A), p‐Tau (P), and total Tau (T). Logistic regression was performed to investigate if grouped inclusion of eleven CSF inflammatory biomarkers as covariates in the models improved classification of baseline clinical diagnosis (CN, cognitively normal; MCI, mild cognitive impairment; Dementia) as well as classification of individuals with and without CMCD one year after baseline.ResultsAt 1‐year follow up, 25.6% experienced CMCD. Inclusion of inflammatory biomarkers improved classification of MCI vs Dementia for models base on DG (p = 0.039) and DGAPT (p = 0.016) feature‐sets. Addition of inflammatory biomarkers to model with DGAPT features, but not the DG model, improved predictive performance for CMCD in CN (p = 0.021) and MCI (p &lt; 0.001) participants.ConclusionsAddition of CSF Inflammatory biomarkers to AD biomarkers can improve diagnostic accuracy of clinical disease stage. Furthermore, inflammatory biomarkers add incremental value to AD biomarkers for prediction of clinical course and cognitive decline.

Association between tongue pressure and oral status and activities of daily living in stroke patients admitted to a convalescent rehabilitation unit.

Clarifying how tongue pressure in convalescent stroke patients affects oral condition andactivities of daily living (ADL) is important for developing oral rehabilitation programs and for rehabilitation care to reacquire ADL. To clarify how tongue pressure is associated with oral status, ADL, and nutritional status in stroke patients. Sixty-eight patients aged 77.9 ± 10.0 years participated. The Japanese version of the Oral Health Assessment Tool was used to evaluate oral status. Data such as the ADL index functional independence measure (FIM), nutritional intake method, serum albumin, and body mass index were extracted from medical records. To examine factors associated with tongue pressure, multiple regression analysis was performed adjusting for confounding factors. The level of statistical significance was set at p < .05. In recovery phase stroke patients, tongue pressure was significantly lower in the total assistance group than in the partial assistance/independent group. In addition, tongue pressure was significantly lower in tube feeding patients than in oral feeding patients. FIM cognition score was an independent factor that had a significant effect on tongue pressure. These findings suggest that ADL status also affects tongue pressure, thus patients' ADL including the FIM cognition subscale should also be evaluated while measuring tongue pressure.

USING A MIDTERM WARNING SYSTEM TO IMPROVE STUDENT PERFORMANCE AND ENGAGEMENT IN AN INTRODUCTORY STATISTICS COURSE: A RANDOMIZED CONTROLLED TRIAL

This article reports on an evaluation the effectiveness of e-mailed grade “nudges” on students’ performance and engagement in an introductory statistics course for undergraduate health science students. In 2020–2021, 358 students were randomized to an e-mail (n = 178) or no e-mail (n = 180) group. The intervention e-mail contained information on each student’s predicted final grade (grade nudge). Using two-sample t-tests, the statistical analysis of final grades in the course showed a higher compatibility with a model of no mean difference for students in the e-mail (73.5%) vs. no e-mail (72.1%) group. Comparison of the distributions of final grades between the two groups, however, suggested the e-mailed nudges may be related to slight improvements in final grades. Specifically, the median final grade was higher in the e-mail group (74.6 vs. 72.4); the Q1 value in the e-mail group was also higher, and the interquartile range was similar: no e-mail group (15.8) vs. e-mail group (14.2). Students also completed the Scale of Student Engagement in Statistics (SSE-S). Total engagement, affective and cognitive subscale scores of the SSE-S were higher in the e-mail group, resulting in low compatibility with a model of no difference in engagement scores. Overall, the results showed there is potential for our midterm warning system to be used to improve outcomes, particularly given that it is simple to implement, cost-effective, and easily scalable.