Change In Mini-Mental State Examination Research Articles

Incidence of 12-month postoperative cognitive decline following regional vs. general anaesthesia in older patients undergoing hip fracture surgery: follow-up of the RAGA trial.

Data regarding the incidence of 12-month postoperative cognitive decline following regional or general anaesthesia in older patients undergoing hip fracture surgery remain observational. Compared with general anaesthesia, we hypothesised that regional anaesthesia would decrease the incidence of 12-month postoperative cognitive decline. This is substudy of a multicentre randomised trial of regional anaesthesia with no sedation vs. general anaesthesia with 12-month follow-up, conducted in nine university hospitals in south-eastern China. Patients aged ≥ 65 y with hip fractures requiring surgery were eligible for inclusion. The prespecified 1-year primary outcome was the incidence of postoperative cognitive decline at 12 months post-randomisation. Secondary outcomes included major or mild postoperative cognitive decline; changes in Mini-Mental State Examination; newly developed dementia; affective status; and health-related quality of life. We recruited 950 patients between October 2014 and September 2018 (n = 474 general and n = 476 regional), with the last participant interviewed in November 2019. A total of 293 patients (139 general vs. 154 regional) were included in the primary analysis of the 12-month outcome. Median (IQR [range]) age of patients was 78 (71-82 [65-96]) y and 217 (74.1%) were female. The incidence of cognitive decline at 12 months was 29.7% vs. 25.4% of patients allocated to general vs. regional anaesthesia, respectively (unadjusted OR 1.2 (95%CI 0.7-2.1), p = 0.43, Bayes factor = 0.28). Major cognitive decline developed in 8.6% vs. 8.5% of patients allocated to general vs. regional anaesthesia, respectively (unadjusted OR 1.0 (95%CI 0.4-2.4)). The incidence of 12-month postoperative cognitive decline was not significantly different in patients having general or regional anaesthesia for hip fracture surgery.

Effects of cilostazol on cognitive function and dementia risk: A systematic review and meta-analysis.

Cilostazol is an antiplatelet drug and is used for stroke prevention and symptomatic peripheral vascular disease. Studies have reported the effects of cilostazol on cognitive function, but the results are inconsistent and have not been systematically assessed. We systematically searched the PubMed, Embase, and Cochrane databases for relevant clinical studies. The primary outcome was the change in Mini-mental State Examination (MMSE) scores from baseline to the last available follow-up. The secondary outcome was dementia risk. Mean differences and 95% confidence intervals (CIs) were calculated for combining MMSE scores, and the pooled odds ratios and 95% CIs were used to calculate the association between use of cilostazol and dementia risk. Overall, 8 eligible studies met inclusion criteria were pooled in meta-analysis. Though with a trend toward favoring cilostazol, the pooled changes in MMSE scores from baseline showed no significant difference in mild cognitive impairment and dementia patients (mean differences 1.02, 95% CI -0.53 to 2.57, P = .195). For secondary outcome, cilostazol reduced the risk of dementia in patients without prior history of dementia (pooled odds ratios 0.90; 95% CI 0.87 to 0.92; P = .000). These results suggest the potential for cilostazol treatment in the suppression of cognitive decline and prevention of progression to dementia. However, the lack of blinding in most studies is likely to cause an overestimation of the effect sizes, and further well-designed studies are also needed.

Long-Range Temporal Correlations in Electroencephalography for Parkinson's Disease Progression.

Patients with Parkinson's disease (PD) present progressive deterioration in both motor and non-motor manifestations. However, the absence of clinical biomarkers for disease progression hinders clinicians from tailoring treatment strategies effectively. To identify electroencephalography (EEG) biomarker that can track disease progression in PD. A total of 116 patients with PD were initially enrolled, whereas 63 completed 2-year follow-up evaluation. Fifty-eight age- and sex-matched healthy individuals were recruited as the control group. All participants underwent EEG and clinical assessments. Long-range temporal correlations (LRTC) of EEG data were analyzed using the detrended fluctuation analysis. Patients with PD exhibited higher LRTC in left parietal θ oscillations (P = 0.0175) and lower LRTC in centro-parietal γ oscillations (P = 0.0258) compared to controls. LRTC in parietal γ oscillations inversely correlated with changes in Unified Parkinson's Disease Rating Scale (UPDRS) part III scores over 2 years (Spearman ρ = -0.34, P = 0.0082). Increased LRTC in left parietal θ oscillations were associated with rapid motor progression (P = 0.0107), defined as an annual increase in UPDRS part III score ≥3. In cognitive assessments, LRTC in parieto-occipital α oscillations exhibited a positive correlation with changes in Mini-Mental State Examination and Montreal Cognitive Assessment scores over 2 years (Spearman ρ = 0.27-0.38, P = 0.0037-0.0452). LRTC patterns in EEG potentially predict rapid progression of both motor and non-motor manifestations in PD patients, enhancing clinical assessment and understanding of the disease. © 2024 International Parkinson and Movement Disorder Society.

Brain function assessment of acupuncture for chronic insomnia disorder with mild cognitive dysfunction based on fNIRS: protocol for a randomized controlled trial.

Chronic Insomnia Disorder (CID) is highly prevalent among older adults and impairs cognitive function. Insomnia accelerates the progression of mild cognitive impairment (MCI) and increases the risk of developing dementia. Acupuncture has been demonstrated in improving sleep quality and cognitive function. This study aims to explore the functional brain characteristics of CID with MCI patients and to assess the effects of acupuncture therapy using functional near-infrared spectroscopy (fNIRS). This study is a single-center randomized controlled trial. Participants will be randomly assigned to the manual acupuncture group or the placebo acupuncture group for an 8-week intervention period. fNIRS data will be collected during resting test and working memory test at baseline and at end of the intervention. The primary outcome is the change of the Montreal Cognitive Assessment (MoCA) score, secondary outcomes include the change of Mini-Mental State Examination (MMSE), Insomnia Severity Index (ISI), Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder Scale (GAD-7), and Apathy Evaluation Scale-Informant (AES-I). The results of the study will provide insights into the effects of acupuncture on sleep quality and cognitive performance in CID with MCI patients. By utilizing fNIRS technology, we will elucidate the neural functional characteristic underlying the therapeutic benefits of acupuncture. https://ClinicalTrials.gov, identifier ChiCTR2300076182.

Association of polygenic liabilities for schizophrenia and bipolar disorder with educational attainment and cognitive aging

To elucidate the specific and shared genetic background of schizophrenia (SCZ) and bipolar disorder (BPD), this study explored the association of polygenic liabilities for SCZ and BPD with educational attainment and cognitive aging. Among 106,806 unrelated community participants from the Taiwan Biobank, we calculated the polygenic risk score (PRS) for SCZ (PRSSCZ) and BPD (PRSBPD), shared PRS between SCZ and BPD (PRSSCZ+BPD), and SCZ-specific PRS (PRSSCZvsBPD). Based on the sign-concordance of the susceptibility variants with SCZ/BPD, PRSSCZ was split into PRSSCZ_concordant/PRSSCZ_discordant, and PRSBPD was split into PRSBPD_concordant/PRSBPD_discordant. Ordinal logistic regression models were used to estimate the association with educational attainment. Linear regression models were used to estimate the associations with cognitive aging (n = 27,005), measured by the Mini-Mental State Examination (MMSE), and with MMSE change (n = 6194 with mean follow-up duration of 3.9 y) in individuals aged≥ 60 years. PRSSCZ, PRSBPD, and PRSSCZ+BPD were positively associated with educational attainment, whereas PRSSCZvsBPD was negatively associated with educational attainment. PRSSCZ was negatively associated with MMSE, while PRSBPD was positively associated with MMSE. The concordant and discordant parts of polygenic liabilities have contrasting association, PRSSCZ_concordant and PRSBPD_concordant mainly determined these effects mentioned above. PRSSCZvsBPD predicted decreases in the MMSE scores. Using a large collection of community samples, this study provided evidence for the contrasting effects of polygenic architecture in SCZ and BPD on educational attainment and cognitive aging and suggested that SCZ and BPD were not genetically homogeneous.

Changes in brain functional connectivity between on and off states and their relationship with cognitive impairment in Parkinson’s disease

Parkinson’s disease (PD) is characterized by motor and non-motor symptoms. Cognitive decline is crucial in disease progression and affect quality of life; however, their underlying mechanisms in PD remain unclear. We explored the relationship between cognitive impairment and functional connectivity (FC) using resting-state functional magnetic resonance imaging in 26 patients with sporadic PD, focusing on the changes in FC between on and off states. Cognitive function was assessed using the Mini-Mental State Examination (MMSE) score. The correlation between MMSE scores and changes in FC values during on and off states was assessed using Pearson’s correlation coefficient. The correlation between changes in FC during the on and off periods and cognitive function differed for each cognitive function item. MMSE memory scores were positively correlated with FC between the brainstem and the left cerebral hemisphere. MMSE attention scores were positively correlated with FC between the bilateral thalamus and frontal lobes and negatively correlated with FC between the left cerebral hemispheres. These findings may facilitate our understanding of the neural correlates underlying cognitive impairment in PD and help develop treatment strategies to preserve cognitive function.

Predicting cognitive function changes from oral health status: a longitudinal cohort study

Recent studies indicate a potential link between oral health and cognitive function; however, long-term associations remain unclear. This study aimed to identify oral health factors that predict changes in cognitive function among older adults over time. The study included 583 independent older adults (201 male, 382 female) with a mean age of 72.7 years. Cognitive function was assessed using Mini-Mental State Examination (MMSE) at baseline and follow-up over two years, with relative change in MMSE (rMMSE) calculated. Baseline oral health variables included number of remaining teeth, masticatory performance, occlusal force, oral diadochokinesis and tongue pressure. Physical performance and confounding factors were also considered. The relationship between rMMSE and the variables was analyzed using Pearson’s correlation, Mann-Whitney U test, and multiple linear regression analysis. Cognitive function declined in 196 subjects, with rMMSE significantly correlated with oral diadochokinesis. Regression analysis revealed significant associations between cognitive changes and oral diadochokinesis (p = 0.020) and knee extension strength as a physical performance (p = 0.047). Our findings suggest that cognitive decline may be indicated by declines in both physical and oral motor performance. Incorporating oral diadochokinesis testing into health screenings could aid early detection of cognitive decline, improving outcomes and reducing healthcare burdens.

Longitudinal trajectories of general cognitive and daily functions in data-driven subtypes of MCI: A longitudinal cohort analysis of older adults

ObjectivesTo derive data-driven subtypes of mild cognitive impairment (MCI) and characterize the complicated changes of general cognitive and daily functions over time in MCI subtypes. MethodsA total of 813 subjects diagnosed as MCI at baseline from the Alzheimer's Disease Neuroimaging Initiative (ADNI) were included. Data-driven MCI subtypes were derived from group-based multi-trajectory modeling (GBMTM) analyses using longitudinal measurement scores in the cognitive domains of visuospatial function, language, and executive function. General cognitive and daily functions were measured by the Mini-Mental State Examination (MMSE) and the Functional Assessment Questionnaire (FAQ), respectively, whose longitudinal trajectory changes were depicted by Linear mixed models. ResultsThree MCI subtypes were derived, which were defined as “Cognitive decline group”, “Mild cognitive decline group” and “No cognitive decline group”. The “Mild cognitive decline group” had the highest percentage in the sample (46.2 %), followed by the “No cognitive decline group” (35.2 %). Patients in the “Cognitive decline group” had the highest mean age (74.69 years) at baseline, the highest APOE ε4 carriers (63.2 %), and the greatest dementia conversion rate (77.0 %). The changes in MMSE and FAQ score trajectories were fastest in the “Cognitive decline group” in the first 36 months and most slowly in the “No cognitive decline group”. ConclusionMCI individuals could be subdivided into more fine-grained cognitive subtypes, and identifying these distinct MCI subtypes and their different trajectories of cognitive decline may have important prognostic value for improving clinical course prediction.

Effects of long-term Tai Chi vs. aerobic exercise on antioxidant activity and cognitive function in individuals with Parkinson’s disease

An imbalance between the generation of reactive oxygen species and the body’s antioxidant defense mechanisms is closely related to the development and progression of Parkinson’s disease (PD). Considering that physical exercise is a potential therapeutic intervention for modulating oxidative stress markers and cognitive function in PD, the primary purpose of this study was to compare the effects of different long-term exercise modalities on antioxidants and cognitive performance in patients with PD. In addition, the secondary purpose was to explore whether changes in the levels of these biochemical markers are associated with alterations in cognitive performance pre- and post-intervention. In all, 61 participants were randomly divided into the aerobic exercise (AE, n=20), Tai Chi exercise (TCE, n=21), or control (n=20) group. Blood samples were collected before and after a 12-week intervention period for the analysis of antioxidant markers [leukocyte 8-hydroxydeoxyguanosine (8-OHdG), catalase (CAT), glutathione (GSH), glutathione peroxidase (GSH-Px), oxidized glutathione (GSSG), superoxide dismutase (SOD), and uric acid (UA)]. Cognitive function was evaluated using the Mini-Mental State Examination (MMSE). Although no significant changes were observed in the activity of 8-OhdG, GSH-Px, GSSG, GSH:GSSG ratio, SOD, and cognitive performance in the AE and TCE groups, the 12-week AE intervention led to a significant increase in CAT and GSH levels, along with a significantly decrease in UA levels among individuals with PD. Conversely, the TCE intervention resulted in a significant increase in GSH levels. However, SOD activity and MMSE scores were significantly decreased after 12 weeks in the control group. The correlations between changes in MMSE scores and changes in the levels of GSH and UA prior to and after the intervention reached significance in the AE group. Thus, long-term AE and TCE might serve as effective strategies for reducing oxidative damage and preserving cognitive function in PD, with AE exhibiting greater benefits compared with TCE. These findings hold potential clinical relevance as complementary measures to standard medical treatments and alternative therapies, such as antioxidant supplements and dietary adjustments, particularly for individuals in the early stages of PD.

Different associations between body mass index and Alzheimer’s markers depending on metabolic health

BackgroundIncreasing evidence supports the association between body mass index (BMI), Alzheimer’s disease, and vascular markers. Recently, metabolically unhealthy conditions have been reported to affect the expression of these markers. We aimed to investigate the effects of BMI status on Alzheimer’s and vascular markers in relation to metabolic health status.MethodsWe recruited 1,736 Asians without dementia (71.6 ± 8.0 years). Participants were categorized into underweight, normal weight, or obese groups based on their BMI. Each group was further divided into metabolically healthy (MH) and unhealthy (MU) groups based on the International Diabetes Foundation definition of metabolic syndrome. The main outcome was Aβ positivity, defined as a Centiloid value of 20.0 or above and the presence of vascular markers, defined as severe white matter hyperintensities (WMH). Logistic regression analyses were performed for Aβ positivity and severe WMH with BMI status or interaction terms between BMI and metabolic health status as predictors. Mediation analyses were performed with hippocampal volume (HV) and baseline Mini-Mental State Examination (MMSE) scores as the outcomes, and linear mixed models were performed for longitudinal change in MMSE scores.ResultsBeing underweight increased the risk of Aβ positivity (odds ratio [OR] = 2.37, 95% confidence interval [CI] 1.13–4.98), whereas obesity decreased Aβ positivity risk (OR = 0.63, 95% CI 0.50–0.80). Especially, obesity decreased the risk of Aβ positivity (OR = 0.38, 95% CI 0.26–0.56) in the MH group, but not in the MU group. Obesity increased the risk of severe WMH (OR = 1.69, 1.16–2.47). Decreased Aβ positivity mediate the relationship between obesity and higher HV and MMSE scores, particularly in the MH group. Obesity demonstrated a slower decline in MMSE (β = 1.423, p = 0.037) compared to being normal weight, especially in the MH group.ConclusionsOur findings provide new evidence that metabolic health has a significant effect on the relationship between obesity and Alzheimer’s markers, which, in turn, lead to better clinical outcomes.

Effects of intraoperative body temperature, blood pressure, cerebral tissue oxygenation, and anesthesia type on postoperative cognitive functions in geriatric arthroplasty surgery for hip fracture.

This study aimed to explore the effects of cerebral oxygenation, body temperature, hemodynamic changes, and anesthesia type on postoperative cognitive dysfunction (POCD) in geriatric patients undergoing hip fracture surgery. One hundred five elderly patients (59 males, 46 females; mean age: 76.7±8.8 years; range, 65 to 95 years) who were scheduled for hip fracture surgery under general or spinal anesthesia between March 2021 and March 2023 were enrolled in the prospective observational study. The cognitive functions were evaluated using the Mini-Mental State Examination (MMSE). Postoperative MMSE values <24 were considered indicative of POCD. Cerebral oxygenation was evaluated before and during the operation using near-infrared spectroscopy (NIRS), and body temperature was measured using a tympanic thermometer, with values <36℃ considered hypothermia. The relationship between decreases in blood pressure ≥30% and POCD was investigated. The relationship between decreases in NIRS of 25% and POCD was also investigated. Postoperative cognitive dysfunction was observed in 29 (27.25%) of the 105 patients. The MMSE value was 24 in 67.06% of 29 patients, and all these patients developed POCD. The incidence of POCD in patients with a preoperative MMSE1 score of 30 was 12.30% (p=0.001). No relationship was identified between MMSE changes and anesthesia type, hypotension, and decreases in the NIRS (p=0.439, p=0.399). Hypothermia was found to be significantly related to POCD (p=0.013). The degree of hypothermia decreased the postoperative MMSE value at different rates. A 1°C body temperature decrease caused a 16.7%, 44.4%, and 50% decrease in MMSE scores of one, one, and two patients, respectively. Hypothermia was found to be significantly related to POCD. The same degree of hypothermia caused different MMSE changes. Since the number of patients with POCD was very low, the effect of amounts of body temperature changes on clinically significant MMSE changes could not be supported by logistic regression. The preoperative MMSE values, MMSE change rates, and age were found to be effective in POCD. Maintaining the body temperature throughout the operation will ensure the preservation of postoperative cognitive functions.

Association of glial fibrillary acid protein, Alzheimer's disease pathology and cognitive decline.

Increasing evidence shows that neuroinflammation is a possible modulator of tau spread effects on cognitive impairment in Alzheimer's disease. In this context, plasma levels of the glial fibrillary acidic protein (GFAP) have been suggested to have a robust association with Alzheimer's disease pathophysiology. This study aims to assess the correlation between plasma GFAP and Alzheimer's disease pathology, and their synergistic effect on cognitive performance and decline. A cohort of 122 memory clinic subjects with amyloid and tau PET, MRI scans, plasma GFAP and Mini-Mental State Examination (MMSE) was included in the study. A subsample of 94 subjects had a follow-up MMSE score at ≥1 year after baseline. Regional and voxel-based correlations between Alzheimer's disease biomarkers and plasma GFAP were assessed. Mediation analyses were performed to evaluate the effects of plasma GFAP on the association between amyloid and tau PET and between tau PET and cognitive impairment and decline. GFAP was associated with increased tau PET ligand uptake in the lateral temporal and inferior temporal lobes in a strong left-sided pattern independently of age, sex, education, amyloid and APOE status (β = 0.001, P < 0.01). The annual rate of MMSE change was significantly and independently correlated with both GFAP (β = 0.006, P < 0.01) and global tau standardized uptake value ratio (β = 4.33, P < 0.01), but not with amyloid burden. Partial mediation effects of GFAP were found on the association between amyloid and tau pathology (13.7%) and between tau pathology and cognitive decline (17.4%), but not on global cognition at baseline. Neuroinflammation measured by circulating GFAP is independently associated with tau Alzheimer's disease pathology and with cognitive decline, suggesting neuroinflammation as a potential target for future disease-modifying trials targeting tau pathology.

Longitudinal assessment of plasma biomarkers for early detection of cognitive changes in subjective cognitive decline.

Individuals experiencing subjective cognitive decline (SCD) are at an increased risk of developing mild cognitive impairment and dementia. Early identification of SCD and neurodegenerative diseases using biomarkers may help clinical decision-making and improve prognosis. However, few cross-sectional and longitudinal studies have explored plasma biomarkers in individuals with SCD using immunomagnetic reduction. To identify plasma biomarkers for SCD. Fifty-two participants [38 with SCD, 14 healthy controls (HCs)] underwent baseline assessments, including measurements of plasma Aβ42, Aβ40, t-tau, p-tau, and α-synuclein using immunomagnetic reduction (IMR) assays, cognitive tests and the Mini-Mental State Examination (MMSE). Following initial cross-sectional analysis, 39 individuals (29 with SCD, 10 HCs) entered a longitudinal phase for reassessment of these biomarkers and the MMSE. Biomarker outcomes across different individual categories were primarily assessed using the area under the receiver operating characteristic (ROC) curve. The SCD subgroup with an MMSE decline over one point was compared to those without such a decline. Higher baseline plasma Aβ1-42 levels significantly discriminated participants with SCD from HCs, with an acceptable area under the ROC curve (AUC) of 67.5% [95% confidence interval (CI), 52.7-80.0%]. However, follow-up and changes in MMSE and IMR data did not significantly differ between the SCD and HC groups (p > 0.05). Furthermore, lower baseline plasma Aβ1-42 levels were able to discriminate SCD subgroups with and without cognitive decline with a satisfied performance (AUC, 75.0%; 95% CI, 55.6-89.1%). At last, the changes in t-tau and Aβ42 × t-tau could differentiate between the two SCD subgroups (p < 0.05). Baseline plasma Aβ42 may help identify people with SCD and predict SCD progression. The role of plasma Aβ42 levels as well as their upward trends from baseline in cases of SCD that progress to mild cognitive impairment and Alzheimer's disease require further investigation.

Dual-Language Use and Cognitive Function Among Mexican Americans Aged 65 and Older.

Better English proficiency and higher frequency of using English among non-native speakers are associated with lower dementia risk. We investigated if Mexican American older adults who use English and Spanish to a more similar degree demonstrate better cognitive function than those who use one language more than the other. We used data from waves one (1992/93) to eight (2012/13) of the Hispanic Established Population for the Epidemiological Study of the Elderly. At baseline, participants were asked what language they usually use across communicative contexts. We based dual language on participants' use of Spanish and English within and across contexts. We categorized participants as low (n = 1,145), medium (n = 717), and high (n = 702) dual-language users. Linear mixed models were used to estimate the association between dual-language use, baseline Mini-Mental State Examination (MMSE) scores, and change in MMSE. Participants in the medium and high dual-language use categories scored 1.91 points and 3.03 points higher at wave one compared to the low dual-language use category. Adjusting for education reduced the association between dual-language use and baseline MMSE (medium B = 0.99 SE = 0.19 p < 0.01; high B = 1.41 SE = 0.21 p < 0.01). The association between dual-language use and decline in the MMSE was not statistically significant. Greater dual-language use was associated with higher MMSE scores but not change in MMSE scores among Mexican Americans aged 65 and older. Future work should characterize bilingualism with greater nuance and use more rigorous cognitive measures to identify the components of the bilingual experience that may benefit the cognitive functioning of older adult bilinguals.

Comparing a pre-defined versus deep learning approach for extracting brain atrophy patterns to predict cognitive decline due to Alzheimer’s disease in patients with mild cognitive symptoms

BackgroundPredicting future Alzheimer’s disease (AD)-related cognitive decline among individuals with subjective cognitive decline (SCD) or mild cognitive impairment (MCI) is an important task for healthcare. Structural brain imaging as measured by magnetic resonance imaging (MRI) could potentially contribute when making such predictions. It is unclear if the predictive performance of MRI can be improved using entire brain images in deep learning (DL) models compared to using pre-defined brain regions.MethodsA cohort of 332 individuals with SCD/MCI were included from the Swedish BioFINDER-1 study. The goal was to predict longitudinal SCD/MCI-to-AD dementia progression and change in Mini-Mental State Examination (MMSE) over four years. Four models were evaluated using different predictors: (1) clinical data only, including demographics, cognitive tests and APOE ε4 status, (2) clinical data plus hippocampal volume, (3) clinical data plus all regional MRI gray matter volumes (N = 68) extracted using FreeSurfer software, (4) a DL model trained using multi-task learning with MRI images, Jacobian determinant images and baseline cognition as input. A double cross-validation scheme, with five test folds and for each of those ten validation folds, was used. External evaluation was performed on part of the ADNI dataset, including 108 patients. Mann-Whitney U-test was used to determine statistically significant differences in performance, with p-values less than 0.05 considered significant.ResultsIn the BioFINDER cohort, 109 patients (33%) progressed to AD dementia. The performance of the clinical data model for prediction of progression to AD dementia was area under the curve (AUC) = 0.85 and four-year cognitive decline was R2 = 0.14. The performance was improved for both outcomes when adding hippocampal volume (AUC = 0.86, R2 = 0.16). Adding FreeSurfer brain regions improved prediction of four-year cognitive decline but not progression to AD (AUC = 0.83, R2 = 0.17), while the DL model worsened the performance for both outcomes (AUC = 0.84, R2 = 0.08). A sensitivity analysis showed that the Jacobian determinant image was more informative than the MRI image, but that performance was maximized when both were included. In the external evaluation cohort from ADNI, 23 patients (21%) progressed to AD dementia. The results for predicted progression to AD dementia were similar to the results for the BioFINDER test data, while the performance for the cognitive decline was deteriorated.ConclusionsThe DL model did not significantly improve the prediction of clinical disease progression in AD, compared to regression models with a single pre-defined brain region.

Vortioxetine Treatment for Depression in Patients with Prodromal vs Mild Alzheimer’s Disease: A Six-Month, Open-Label, Observational Study

BackgroundDepressive symptoms are common in Alzheimer disease (AD) from the prodromal stage. The benefits of antidepressants have been investigated in patients with AD dementia with mixed results.ObjectivesThis study aimed to compare the efficacy of vortioxetine in prodromal and mild-to-moderate AD patients with depression, and to assess the comparative effect on secondary measures, including behavioral disturbances, cognitive function, and activities of daily living.ParticipantsAll subjects with AD at a single-center dementia center underwent a standard evaluation with mini-mental state examination (MMSE), basic and instrumental activities of daily living (BADL and IADL), geriatric depression scale (CDS), neuropsychiatrie inventory (NPI), and clinical evaluation every six months.MeasurementsThe study specifically assessed patients on vortioxetine with available six-month follow-up data. The changes in CDS, NPI, MMSE, BADL/IADL at six months in the entire AD population and mild-to-moderate AD vs prodromal population were analyzed using repeated measure multivariate analyses. Linear regression analyses were implemented to evaluate baseline demographics and clinical characteristics associated with depressive and cognitive improvements at six months.ResultsOut of 680 AD patients, 115 were treated with vortioxetine, and 89 with six-month follow-up data were included in the analyses. A significant improvement at follow-up was observed for CDS, NPI total and sub score items (mood, anxiety, apathy, sleep disturbances, eating abnormalities). Both mild-to-moderate and prodromal AD showed a positive CDS response, whereas mild-to-moderate AD showed a better improvement on total NPI and apathy/nighttime behaviors subitems compared to prodromal AD. Higher baseline CDS score was the only variable associated with higher responses in linear regression analyses. MMSE showed a significant improvement at six months in the entire cohort, with a greater effect in prodromal vs mild-to-moderate AD. Cognitive improvement (i.e., MMSE changes) was associated with cognitive status at baseline but independent of the antidepressant/behavioral changes (i.e., GDS/NPI).ConclusionsOur results suggest that vortioxetine is highly tolerable and clinically effective in both prodromal and mild-to-moderate AD with depression. Patients with mild-to-moderate AD benefited more from a wide range of behavioral disturbances. The study also showed significant improvement in global cognitive measures, especially in prodromal AD subjects. Further studies are needed to investigate the independent beneficial effect of vortioxetine on depression and cognition in AD.

Examination of the proportion and characteristics of cognitive function changes during hospitalization in patients with cardiovascular diseases.

Cognitive function decline is influenced by cardiovascular diseases and associated risk factors. However, changes in the cognitive function of patients with cardiovascular diseases during hospitalization and the factors influencing these changes remain unclear. This study elucidated the proportion and characteristics of changes in cognitive function during hospitalization in patients with cardiovascular diseases. We conducted cognitive function assessments at admission and discharge for patients with cardiovascular diseases. Using the Mini-Mental State Examination (MMSE) and the Japanese version of the Montreal Cognitive Assessment (MoCA-J), we categorized the patients into cognitive impairment, mild cognitive impairment (MCI), and non-cognitive impairment. Changes in MMSE or MoCA-J scores of ≥2 points at discharge were classified as improvement or decline, and all others as maintenance. The cognitive impairment, MCI, and non-cognitive impairment categories comprised 215 (41.3%), 224 (40.2%), and 103 (18.5%) patients, respectively. The results of the cognitive function assessment at the time of discharge classified 90 patients (35.9%) into the maintenance group, 117 (46.6%) into the improvement group, and 44 (17.5%) into the decline group based on changes during hospitalization. There was a statistically significant difference among the three groups only in cognitive function at admission (P = 0.026). In multivariate analysis, those with MCI or cognitive impairment at admission and younger patients were associated with improved cognitive function during hospitalization. No factors were extracted that showed statistically significant associations with cognitive decline. Approximately half of the patients with cardiovascular disease experienced improvements in cognitive function during hospitalization, while approximately 20% showed a decline in cognitive function during the same period. These findings demonstrate the importance of assessing cognitive changes in hospitalized patients with cardiovascular disease. Future studies are needed to identify factors associated with changes in cognitive function.

Evaluation of the association between circulatory markers of neuroinflammation and Alzheimer’s disease pathology

AbstractBackgroundIncreasing evidence suggests that neuroinflammation and astrogliosis have a prominent role in the spread of pathology and the development of cognitive impairment in Alzheimer’s disease (AD). Circulating plasma markers of neuroinflammation, such as the glial fibrillary acid protein (GFAP), have recently become available, and early observations suggest a robust association with brain pathology. Positron emission tomography (PET) is a molecular imaging technique that allows visualisation and quantification of AD pathology in vivo. The aim of this study was to evaluate the association between GFAP and AD pathology, and its interaction with cognitive decline.Method121 subjects from the Geneva Memory Centre underwent amyloid and tau PET, blood collection, and mini‐mental state examination (MMSE). Amyloid uptake was calculated as centiloid whereas tau was quantified as standardised uptake value ratio. Association of centiloid and tau with GFAP was assessed using a multivariate linear regression model, corrected for age, gender, and MMSE. Mediation analysis described the mediating effect of GFAP on the association between centiloid and tau. Ninety‐four subjects had a follow‐up MMSE after at least 12 months. Linear regression was used to assess the effect of GFAP on the annual rate of change of MMSE (corrected for centiloid, global tau, age, and gender). Mediation analysis was used to test whether the relationship between rate of MMSE change and tau could be explained by a mediation of GFAP.ResultThe mean (SD) age of the participants was 72.6 (7.6) years, and 61 of 121 subjects were men. GFAP was significantly associated with increased tau, but not with centiloid. GFAP partially mediated the effect of centiloid on global tau (mediated proportion = 14%, p = 0.03). The rate of MMSE change was significantly associated with GFAP, and global tau, but not with centiloid. Moreover, GFAP partially mediated the effect between global tau SUVR and change of MMSE scores (52%, p&lt;0.01).ConclusionElevated GFAP is associated with tau. GFAP also partially explains the effect of amyloid pathology on tau accumulation and of tau pathology on subsequent cognitive decline. These results support neuroinflammation and astrogliosis as a relevant contributor to AD pathology, which can be monitored in blood.

Effect of Virgin Coconut Oil on Cognition of Mild‐to‐moderate Alzheimer’s Disease Patients with APOE ε4 Allele

AbstractBackgroundVirgin coconut oil (VCO) is an excellent source of medium chain fatty acids and thus, a potential natural ketogenic agent that can be used to substitute glucose in Alzheimer’s disease (AD) brain, in which the glucose metabolism is compromised. High content of polyphenols in VCO will also support to reduce inflammation and oxidative stress associated with AD. The aims of this double‐blind placebo‐controlled trial were to investigate the effect of VCO on cognition in mild‐to‐moderate AD patients and the association of apolipoprotein E (APOE) ε4 genotype on the outcome.MethodStudy participants were 120 mild‐to‐moderate AD patients [Mini‐Mental State Examination (MMSE) score = 15‐25, age ≥65 years], randomly allocated to either treatment or control groups and orally fed 30 mL/ day of VCO as the treatment and a same amount of canola oil as the placebo for 24 weeks. Cognition was assessed by MMSE, Montreal Cognitive Assessment (MOCA), and executive clock drawing task (CLOX) at the baseline and at the end of the intervention. APOE genotyping was conducted at the baseline. Fasting lipid profile and glycated hemoglobin (HbA1C) levels were analyzed at the baseline and at the end of the intervention.ResultThere was no significant difference in the post‐intervention changes of cognitive assessment scores, lipid profile and HbA1C levels between the treatment and control groups. The MMSE scores of the APOE ε4 carriers in the treatment group was improved compared to the non‐carriers (change of MMSE = 2.37, p = 0.021), whereas there was no difference in the control group. In both treatment and control groups, the lipid parameters were not compromised during the intervention.ConclusionOral supplementation of 30 mL/day of VCO for 24 weeks did not improve cognition of mild‐to‐moderate AD patients compared to canola oil. However, VCO improved the MMSE scores of APOE ε4 carriers compared to non‐carriers. Consumption of VCO was safe as it did not compromise lipid parameters.

Multipredictor risk models for predicting individual risk of Alzheimer’s disease

BackgroundEarly prevention of Alzheimer’s disease (AD) is a feasible way to delay AD onset and progression. Information on AD prediction at the individual patient level will be useful in AD prevention. In this study, we aim to develop risk models for predicting AD onset at individual level using optimal set of predictors from multiple features.MethodsA total of 487 cognitively normal (CN) individuals and 796 mild cognitive impairment (MCI) patients were included from Alzheimer's Disease Neuroimaging Initiative. All the participants were assessed for clinical, cognitive, magnetic resonance imaging and cerebrospinal fluid (CSF) markers and followed for mean periods of 5.6 years for CN individuals and 4.6 years for MCI patients to ascertain progression from CN to incident prodromal stage of AD or from MCI to AD dementia. Least Absolute Shrinkage and Selection Operator Cox regression was applied for predictors selection and model construction.ResultsDuring the follow-up periods, 139 CN participants had progressed to prodromal AD (CDR ≥ 0.5) and 321 MCI patients had progressed to AD dementia. In the prediction of individual risk of incident prodromal stage of AD in CN individuals, the AUC of the final CN model was 0.81 within 5 years. The final MCI model predicted individual risk of AD dementia in MCI patients with an AUC of 0.92 within 5 years. The models were also associated with longitudinal change of Mini-Mental State Examination (p < 0.001 for CN and MCI models). An Alzheimer’s continuum model was developed which could predict the Alzheimer’s continuum for individuals with normal AD biomarkers within 3 years with high accuracy (AUC = 0.91).ConclusionsThe risk models were able to provide personalized risk for AD onset at each year after evaluation. The models may be useful for better prevention of AD.