Change In Mini-Mental State Examination Score Research Articles

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

Background: Better English proficiency and higher frequency of using English among non-native speakers are associated with lower dementia risk. Objective: 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. Methods: 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. Results: 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. Conclusions: 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.

Is Virtual Reality Orientation Therapy Useful to Optimize Cognitive and Behavioral Functioning Following Severe Acquired Brain Injury? An Exploratory Study.

Severe acquired brain injury (SABI) is a leading cause of death and disability, and it is defined as a brain injury that occurs after birth due to traumatic or non-traumatic causes. Reality orientation therapy (ROT) uses repeated time-place-person orientation and meaningful stimuli to develop a better understanding of the environment and has great potential as an effective strategy to improve cognitive and behavioral functioning. This study aims to investigate the feasibility and potential effects of virtual reality orientation therapy (VR-rot) on optimizing cognitive and behavioral functioning and depressive symptoms post-SABI. Forty patients with SABI were enrolled from October 2022 to December 2023 and divided into two groups: the experimental group (EG, n = 20) received VR_rot, while the control group (CG, n = 20) received standard ROT (S_rot). All patients were evaluated with a psychometric battery, including the Mini-Mental State Examination (MMSE) and the Hamilton Rating Scale for Depression (HRS-D), administered before (T0) and after the end (T1) of rehabilitation. Within-group comparisons indicated a statistically significant change in MMSE scores from T0 to T1 in the EG and CG, with the EG showing a greater improvement than the CG. Regarding HRS-D scores, the EG showed a statistically significant change. VR-ROT could be a valuable tool for improving cognitive-behavioral functioning in SABI patients. The VRRS can help reduce depressive symptoms and improve the reality orientation deficit caused by traumatic brain injury and stroke on brain tissue. This study highlights the benefits of virtual reality.

Mediterranean diet related to 3-year incidence of cognitive decline: results from a cohort study in Chinese rural elders

ABSTRACT Objective This study aims to examine the effect of the Mediterranean diet (MeDi) on cognitive decline among the Chinese elderly with a 3-year follow-up. Methods This study is divided into two waves: wave-1 January 2019 to June 2019 (n = 2313); wave-2 January 2022 to March 2022 (n = 1648). MeDi scores were calculated from the Mediterranean Diet Adherence Screener (MEDAS), with the scoring of low compliance (0–6 points) and high compliance (7–14 points). The Mini-Mental State Examination (MMSE) was used to assess cognitive function. An MMSE score dropping ≥ 2 points from baseline was defined as cognitive decline. The relationships between MeDi score and cognitive decline were analyzed by linear regression models or Binary logistic regression. Results During the 3-year follow-up, 23.8% of patients exhibited cognitive decline. The study revealed a significant difference in MMSE score changes between low and high MeDi adherence groups (p < 0.001). MeDi score was negatively correlated with cognitive deterioration (β = −0.020, p = 0.026). MeDi score was only negatively associated with cognitive decline in the female subgroup aged ≥65 years (β = −0.034, p = 0.033). The food beans (OR = 0.65, 95%CI:0.51, 0.84), fish (OR = 0.72, 95%CI:0.54, 0.97), and cooked vegetables (OR = 0.68, 95%CI:0.53, 0.84) were protective factors for cognitive decline. Conclusions This study suggests that greater adherence to the MeDi is linked to a reduced risk of cognitive decline in elderly people. However, this is found only in women who are 65 years old or older. It also found long-term adherence to beans, fish, and vegetables are more effective in improving cognitive function.

Sex differences in cognitive function trajectories and their determinants in older adults: Evidence from the Chinese longitudinal healthy longevity survey.

To examine sex differences in the cognitive trajectories of a nationally representative sample of older people living in China and to explore potential determinants of these trajectories. The study included 2230 women and 2171 men who were cognitively healthy and aged over 60 at the first observation from the Chinese Longitudinal Healthy Longevity Survey based on the 2008-2018 cohort. Cognitive function was measured using the Chinese version of the Mini-Mental State Examination (MMSE). Group-based trajectory modeling was used to identify potential heterogeneity of longitudinal changes over the 10years in each gender. Logistic regression was used to investigate associations between baseline characteristics (age, education, fertility history, sleep length, physical activity, and health status and behaviors) and trajectory classes. Three trajectories (labeled stable, slow decline, and rapid decline) were identified according to the changes in MMSE scores for both women and men. For the women, both the slow and rapid decline groups accounted for a larger proportion (14.7% and 11.0%, respectively) than the male decline groups (8.1% and 6.6%, respectively), and the women had a lower baseline MMSE score with a faster decline. In the multivariable logistic regression analyses, older age, less education, older age at first birth, poorer functional abilities, hearing impairment, and lower baseline MMSE scores were significantly associated with cognitive decline in both the female and male groups compared to the stable group. For the women, sleeping over 9h was also associated with a rapid cognitive decline trajectory, while current exercise and being overweight/obese were protective factors against cognitive decline. The women had an overall more serious cognitive decline than men. The potential determinants of cognitive decline identified in this study could be considered for developing specific intervention strategies aimed at promoting a healthy brain and preventing cognitive decline in different sexes, especially in low-income and developing countries.

Dementia subtypes, cognitive decline and survival among older adults attending a memory clinic in Cape Town, South Africa: a retrospective study

BackgroundThere are no published longitudinal studies from Africa of people with dementia seen in memory clinics. The aim of this study was to determine the proportions of the different dementia subtypes, rates of cognitive decline, and predictors of survival in patients diagnosed with dementia and seen in a memory clinic.MethodsData were collected retrospectively from clinic records of patients aged ≥ 60 seen in the memory clinic at Groote Schuur Hospital, Cape Town, South Africa over a 10-year period. Diagnostic and Statistical Manual of Mental Disorders (DSM–5) criteria were used to identify patients with Major Neurocognitive Disorders (dementia). Additional diagnostic criteria were used to determine the specific subtypes of dementia. Linear regression analysis was used to determine crude rates of cognitive decline, expressed as mini-mental state examination (MMSE) points lost per year. Changes in MMSE scores were derived using mixed effects modelling to curvilinear models of cognitive change, with time as the dependent variable. Multivariable cox survival analysis was used to determine factors at baseline that predicted mortality.ResultsOf the 165 patients who met inclusion criteria, 117(70.9%) had Major Neurocognitive Disorder due to Alzheimer’s disease (AD), 24(14.6%) Vascular Neurocognitive Disorder (VND), 6(3.6%) Dementia with Lewy Bodies (DLB), 5(3%) Parkinson disease-associated dementia (PDD), 3(1.8%) fronto-temporal dementia, 4(2.4%) mixed dementia and 6(3.6%) other types of dementia. The average annual decline in MMSE points was 2.2(DLB/PDD), 2.1(AD) and 1.3(VND). Cognitive scores at baseline were significantly lower in patients with 8 compared to 13 years of education and in those with VND compared with AD. Factors associated with shorter survival included age at onset greater than 65 (HR = 1.82, 95% C.I. 1.11, 2.99, p = 0.017), lower baseline MMSE (HR = 1.05, 95% C.I. 1.01, 1.10, p = 0.029), Charlson’s comorbidity scores of 3 to 4 (HR = 1.88, 95% C.I. 1.14, 3.10, p = 0.014), scores of 5 or more (HR = 1.97, 95% C.I. 1.16, 3.34, p = 0.012) and DLB/PDD (HR = 3.07, 95% C.I. 1.50, 6.29, p = 0.002). Being female (HR = 0.59, 95% C.I.0.36, 0.95, p = 0.029) was associated with longer survival.ConclusionsKnowledge of dementia subtypes, the rate and factors affecting cognitive decline and survival outcomes will help inform decisions about patient selection for potential future therapies and for planning dementia services in resource-poor settings.

Efficacy and Safety of Cilostazol in Mild Cognitive Impairment

Recent evidence indicates the efficacy of β-amyloid immunotherapy for the treatment of Alzheimer disease, highlighting the need to promote β-amyloid removal from the brain. Cilostazol, a selective type 3 phosphodiesterase inhibitor, promotes such clearance by facilitating intramural periarterial drainage. To determine the safety and efficacy of cilostazol in mild cognitive impairment. The COMCID trial (A Trial of Cilostazol for Prevention of Conversion from Mild Cognitive Impairment to Dementia) was an investigator-initiated, double-blind, phase 2 randomized clinical trial. Adult participants were registered between May 25, 2015, and March 31, 2018, and received placebo or cilostazol for up to 96 weeks. Participants were treated in the National Cerebral and Cardiovascular Center and 14 other regional core hospitals in Japan. Patients with mild cognitive impairment with Mini-Mental State Examination (MMSE) scores of 22 to 28 points (on a scale of 0 to 30, with lower scores indicating greater cognitive impairment) and Clinical Dementia Rating scores of 0.5 points (on a scale of 0, 0.5, 1, 2, and 3, with higher scores indicating more severe dementia) were enrolled. The data were analyzed from May 1, 2020, to December 1, 2020. The participants were treated with placebo, 1 tablet twice daily, or cilostazol, 50 mg twice daily, for up to 96 weeks. The primary end point was the change in the total MMSE score from baseline to the final observation. Safety analyses included all adverse events. The full analysis set included 159 patients (66 [41.5%] male; mean [SD] age, 75.6 [5.2] years) who received placebo or cilostazol at least once. There was no statistically significant difference between the placebo and cilostazol groups for the primary outcome. The least-squares mean (SE) changes in the MMSE scores among patients receiving placebo were -0.1 (0.3) at the 24-week visit, -0.8 (0.3) at 48 weeks, -1.2 (0.4) at 72 weeks, and -1.3 (0.4) at 96 weeks. Among those receiving cilostazol, the least-squares mean (SE) changes in MMSE scores were -0.6 (0.3) at 24 weeks, -1.0 (0.3) at 48 weeks, -1.1 (0.4) at 72 weeks, and -1.8 (0.4) at 96 weeks. Two patients (2.5%) in the placebo group and 3 patients (3.8%) in the cilostazol group withdrew owing to adverse effects. There was 1 case of subdural hematoma in the cilostazol group, which may have been related to the cilostazol treatment; the patient was successfully treated surgically. In this randomized clinical trial, cilostazol was well tolerated, although it did not prevent cognitive decline. The efficacy of cilostazol should be tested in future trials. ClinicalTrials.gov Identifier: NCT02491268.

Predictive Ability of Frontal Assessment Battery for Cognitive Improvement After Shunt Surgery in Individuals With Idiopathic Normal Pressure Hydrocephalus.

The predictive ability of the Frontal Assessment Battery (FAB) for postoperative cognitive improvement in idiopathic normal pressure hydrocephalus (iNPH) is unstudied. To compare the predictive ability of the FAB and the Mini-Mental State Examination (MMSE) for postoperative cognitive improvement in individuals with iNPH after shunt surgery. We retrospectively reviewed the medical records of individuals with iNPH who had shunt surgery between January 2016 and October 2018. Individuals had completed the tap test and clinical evaluations (FAB, MMSE, Timed Up and Go [TUG]) both before and 24-48 hours after CSF tapping and after surgery. We excluded individuals without complete clinical evaluations and those with shunt surgery performed >6 months after CSF tapping. Factors associated with postoperative FAB and MMSE improvement as per the 2011 iNPH guidelines were extracted using univariate and multivariate logistic regression analyses. Independent variables were baseline FAB and MMSE scores, FAB and MMSE score changes and TUG amelioration rate after CSF tapping, Evans index, age, and days from CSF tapping to surgery and from surgery to postoperative assessment. The mean number of days from CSF tapping to surgery and from surgery to postoperative assessment were 77.5 (SD = 36.0) and 42.0 (SD = 14.5), respectively. Logistic regression analyses showed significant associations in the univariate analyses of postoperative FAB improvement with baseline FAB scores ( P = 0.043) and with FAB score changes after CSF tapping ( P = 0.047). The FAB may help predict postoperative cognitive improvement after shunt surgery better than the MMSE.

Progression of brain cholinergic dysfunction in patients with isolated rapid eye movement sleep behavior disorder.

Reduced cortical acetylcholinesterase activity, as measured by 11 C-donepezil positron emission tomography (PET), has been reported in patients with isolated rapid eye movement (REM) sleep behavior disorder (iRBD). However, its progression and clinical implications have not been fully investigated. Here, we explored the relationship between longitudinal changes in brain acetylcholinesterase activity and cognitive function in iRBD. Twelve iRBD patients underwent 11 C-donepezil PET at baseline and after 3 years. PET images were interrogated with statistical parametric mapping (SPM) and a regions of interest (ROI) approach. Clinical progression was assessed with the Movement Disorder Society-Unified Parkinson's Disease Rating Scale-Part III (MDS-UPDRS-III). Cognitive function was rated using the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA). From baseline to follow-up, the mean 11 C-donepezil distribution volume ratio (DVR) decreased in the cortex (p = 0.006), thalamus (p = 0.013), and caudate (p = 0.013) ROI. Despite no significant changes in the group mean MMSE or MoCA scores being observed, individually, seven patients showed a decline in their scores on these cognitive tests. Subgroup analysis showed that only the subgroup of patients with a decline in cognitive scores had a significant reduction in mean cortical 11 C-donepezil DVR. Our results show that severity of brain cholinergic dysfunction in iRBD patients increases significantly over 3 years, and those changes are more severe in those with a decline in cognitive test scores.

Association of dietary patterns with cognitive function in older people: Results from the Chinese longitudinal healthy longevity survey

AbstractBackgroundDietary patterns are crucial for maintaining cognitive health among older people and can be modified through lifestyle interventions. We investigated the associations between dietary patterns, changes in these patterns over time, and cognitive function.MethodsThis cohort study utilized data from the Chinese Longitudinal Healthy Longevity Survey conducted between 2005 and 2014. The sample included 7472 participants (mean age: 81.45 ± 10.88 years). Dietary patterns were derived using cluster analysis. Cognitive function was assessed using the Mini‐Mental State Examination (MMSE). The relationships between dietary patterns/changes, MMSE scores, changes in MMSE scores, and cognitive impairment were analyzed using the generalized estimating equation method, linear regression, and logistic regression.ResultsCluster analysis identified three major dietary patterns: balanced diet, relatively balanced diet, and unbalanced diet. Mean MMSE scores decreased from 24.71 ± 7.24 in 2005 to 22.22 ± 9.29 in 2008, then increased to 24.10 ± 7.76 in 2014. Participants who adhered to balanced diet patterns exhibited significantly higher MMSE scores (1.56; 95% confidence interval: 1.34, 1.78) than those who followed unbalanced diet patterns. This association was particularly prominent among older individuals, women, individuals with no education, and underweight individuals. Participants with relatively balanced or balanced diets showed a significantly lower risk of cognitive impairment (adjusted odds ratio (OR) = 0.72, 95% CI: 0.65, 0.80; OR = 0.47, 95% CI: 0.42, 0.53, respectively) than those with unbalanced diets. Transitioning from an unhealthy diet to a healthy diet was associated with a smaller decline in MMSE scores and reduced risk of cognitive impairment.ConclusionsThese findings emphasize the importance of balanced or relatively balanced diets in preserving cognitive health in older individuals. These patterns relate to better MMSE scores and reduced cognitive impairment risk. Shifting from unhealthy to healthy diets is linked to improved MMSE scores and lower cognitive impairment risk. These results underscore the importance of dietary interventions in mitigating cognitive decline in older adults. Further research is warranted to understand the underlying mechanisms and develop targeted strategies for promoting healthy dietary habits in this population.

Fluctuations in Cognitive Test Scores and Loss to Follow-Up in Community-Dwelling Older Adults: The IRIDE Cohort Study

Introduction: We examined the relationship between previous fluctuations in Mini-Mental State Examination (MMSE) scores, future changes in MMSE scores, and attrition from follow-up surveys, which helps in a more comprehensive interpretation of repeatedly collected MMSE scores. Methods: This 4-year longitudinal study included 2,073 community-dwelling older adults aged ≥65 years in Japan. The MMSE was administered at baseline (T0), 2 years (T1), and 4 years (T2) follow-up. We performed multinomial logistic regression analysis with the dependent variable, indicating the change in MMSE score from T1 to T2 (categorized as increase, no change [reference category], and decrease) and attrition at T2. The independent variables included the change in MMSE scores from T0 to T1 and MMSE scores at T0 and T1. Results: The mean MMSE score was 29 across the three time points. A one-point decrease in MMSE score from T0 to T1 was associated with 79% (95% confidence interval: 1.62, 1.97) higher odds of an increase in MMSE score from T1 to T2 and 28% (1.17, 1.40) higher odds of attrition at T2. A one-point decrement in the MMSE score at T0 and T1 was also associated with an increase in the MMSE score from T1 to T2 and attrition at T2. Conclusion: Focusing on cognitive fluctuation for 2 years, rather than cognitive function at a point in time, would have no remarkable advantage when focusing on future cognitive function and attrition. Our results emphasize the need for further studies to identify factors that distinguish between those who continue to attend follow-up surveys and show improvements in cognitive test scores and those who drop out.

Effect of famotidine on cognitive and behavioral dysfunctions induced in post-COVID-19 infection: A randomized, double-blind, and placebo-controlled study

ObjectivesThis is an investigation of the efficacy and safety of famotidine, a selective histamine H2 receptor antagonist, on improvement of cognitive impairment, depression and anxiety symptoms developing post-COVID-19, in a 12-week, randomized controlled trial. MethodsA total of 50 patients with a confirmed diagnosis of COVID-19 and a score ≤ 23 on the Mini-Mental State Examination (MMSE) test or a score ≤ 22 on the Montreal Cognitive Assessment (MoCA) were randomly assigned to either the famotidine (40 mg twice daily) or the placebo group. Changes in MMSE scores at weeks 6 and 12 were the primary outcome, while changes in other scales were the secondary outcomes. Participants and evaluators were blinded. ResultsAt weeks 6 and 12, patients in the famotidine group had significantly higher MMSE scores (p = 0.014, p < 0.001, respectively). Regarding the MoCA scale, the famotidine group had a significantly higher score at weeks 6 and 12 (p = 0.001, p < 0.001, respectively). Considering the HAM-D scale (Hamilton Depression Rating Scale), at weeks 6 and 12, the famotidine group experienced a larger reduction (p = 0.009, p = 0.02, respectively). Additionally, comparison of the HAM-A scale scores (Hamilton Anxiety Rating Scale) at weeks 6 and 12 showed a statistically significant larger reduction in the famotidine group (p = 0.04, p = 0.02, respectively). The two groups did not differ in the frequency of adverse effects. ConclusionOur study supports safety and efficacy of famotidine in treating cognitive impairment, depression and anxiety symptoms induced by COVID-19. Trial registrationThis trial was registered at the Iranian registry of clinical trials (IRCT: www.irct.ir; registration number: IRCT20090117001556N138).

Protecting cognitive function in older adults with age-related hearing loss: Insights from The Irish Longitudinal Study on Ageing (TILDA) and the role of hearing aids

BackgroundAge-related hearing loss (ARHL) is prevalent in adults over 70, impairing hearing sensitivity and speech perception. ARHL has been linked to an increased risk of cognitive decline and dementia. However, most affected adults are not receiving adequate treatment, including hearing aids. ObjectiveThis study aimed to evaluate the impact of ARHL on cognitive decline in older adults participating in the Irish Longitudinal Study on Aging (TILDA). Design: MethodsData from four TILDA waves, a 6-year follow-up, was collected and analyzed using zero-inflated Poisson regression. The primary outcome, cognitive function, was assessed using Mini-Mental State Examination (MMSE) total score and error counts. ResultsOur analysis revealed that age, education, use of aids to help with hearing, and history of stroke were significantly associated with error counts at baseline. Additionally, poor hearing was associated with a negative change in MMSE score from wave 4, indicating the potential role of ARHL in cognitive decline. When further adjusted for age, sex, history of stroke, hypertension, any emotional, nervous, or psychiatric problem, polypharmacy, and hearing aids, the zero-inflated Poisson model indicated that poor hearing, use of hearing aids, stroke, hypertension, and polypharmacy all predicted MMSE error counts in follow-up assessments. Moreover, the use of hearing aids was associated with a decreased likelihood of cognitive decline. ConclusionARHL was independently associated with cognitive decline, underscoring the importance of addressing hearing loss in older adults. Future research should explore the potential of hearing aids to protect cognitive functioning in older adults.

Circadian rest-activity rhythm and longitudinal brain changes underlying late-life cognitive decline.

The neurobiological substrates underlying the relationship of circadian rest-activity rhythm (RAR) alteration with accelerated late-life cognitive decline are not clearly understood. In the present study, the longitudinal relationship of objectively measured circadian RAR with in vivo Alzheimer disease (AD) pathologies and cerebrovascular injury was investigated in older adults without dementia. The present study included 129 participants without dementia who participated in the KBASE (Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer's Disease) cohort. All participants underwent actigraphy at baseline and two consecutive [11 C] Pittsburgh compound-B positron emission tomography (PET), [18 F] fluorodeoxyglucose-PET, magnetic resonance imaging, and Mini-Mental State Examination (MMSE) at baseline and at a 2-year follow-up assessment. The associations of circadian RAR with annualized change in neuroimaging measures including global amyloid-beta retention, AD-signature region cerebral glucose metabolism (AD-CM), and white matter hyperintensity volume were examined. Delayed acrophase at baseline was significantly associated with greater annualized decline of AD-CM over a 2-year period, but not with that of other neuroimaging measures. In contrast, other circadian RAR parameters at baseline had no association with annualized change of any neuroimaging measures. Annualized decline of AD-CM was also significantly positively associated with the annual change in MMSE scores. Furthermore, a mediation analysis showed that greater reduction in AD-CM mediated the effect of delayed acrophase at baseline on faster decline of MMSE score. The findings indicate that delayed acrophase in late life may cause or predict hypometabolism at AD-signature brain regions, which underlies cognitive decline in the near future.

Geo‐Cultural Influence on Change in CDR and MMSE Scores

AbstractBackgroundAlzheimer’s disease (AD) clinical trials are increasingly global. Most measures used were validated and standardized with North American, White, English‐speaking populations with limited consideration of cultural nuance. Prior research suggests that both the Clinical Dementia Rating (CDR) and Mini Mental State Examination (MMSE) are not free from cultural and linguistic influence. It is important to understand how geo‐cultural factors influence longitudinal change in scores on these measures, which is often used as the primary endpoint for study efficacy. In this study, we examined whether change in CDR and MMSE scores over one‐year follow‐up varied across geo‐cultural regions.MethodThis study included electronic CDR (eCDR) and electronic MMSE (eMMSE) data from four multi‐national AD clinical trials of subjects with prodromal to mild AD. Data were collected at screening and one‐year follow‐up from seven geo‐cultural regions: East Asia (n = 138); Eastern Europe (n = 170); Western Europe (n = 484); North America (n = 496); South America (n = 55); Middle East/Africa (n = 26); and Oceania (n = 26).ResultThe Kruskal–Wallis test found statistically significant variance in CDR‐Sum of Box (CDR‐SB) scores across geo‐cultural regions (p &lt;0.0001). Results of the Dunn’s test indicated mean change in CDR‐SB scores for South America was significantly lower than those for North America, Eastern Europe, Western Europe, and Mideast/Africa. Additionally, mean change in CDR‐SB scores for East Asia was significantly lower than those for Western and Eastern Europe. Change in MMSE total scores did not vary across geo‐cultural regions.ConclusionOur study found average change in CDR‐SB but not MMSE total scores differed significantly across geo‐cultural regions. CDR‐SB scores were relatively more stable in South America compared to most other regions, and in East Asia compared to Western/Eastern Europe. The CDR may be more susceptible to cultural factors due to its reliance on subjective information from caregivers, in contrast with the MMSE, a standardized, objective measure. Different social norms and expectations for aging, functional independence, and trial participation in these regions may have contributed to the variance. Future studies should examine if specific CDR or MMSE items are more contextually dependent on the local culture.

Effects of Depression on Changes in Cognitive Function in Older Adults: A Fixed-effects Model Analysis Using the Korean Longitudinal Study of Aging (KLoSA).

This study identified the rate of change in cognitive function of community-based middle-aged and older adults and investigated the longitudinal effects of depression, health status, and health behavior by cognitive function group [normal, mild cognitive impairment (MCI), dementia] using data from the Korean Longitudinal Study of Aging. This longitudinal panel analysis collected 21,425 data points from 4285 participants. Cognitive function change patterns in the groups were examined through descriptive analysis. A fixed-effects model was estimated using demographic factors, such as depression, health behavior, and disease states as independent variables. Compared with the baseline score of the mini-mental state examination (MMSE), the 8-year mean score decreased by 10.51, 8.6, and 1.21 for the dementia, MCI, and normal groups, respectively. The estimates for the normal group showed that an increase in the depression score significantly negatively impacted the MMSE score (B=-0.059, P <0.001). However, compared with those of the MCI group (B=-0.044, P >0.05), the estimates of the dementia group confirmed that depression significantly negatively affected cognitive function (B=-0.146, P <0.05). Each group showed different patterns of cognitive decline. An annual follow-up cognitive impairment screening to investigate changes in MMSE score in community-based older individuals can enable early detection of dementia.

Extracellular microRNA and cognitive function in a prospective cohort of older men: The Veterans Affairs Normative Aging Study.

Background: Aging-related cognitive decline is an early symptom of Alzheimer’s disease and other dementias, and on its own can have substantial consequences on an individual’s ability to perform important everyday functions. Despite increasing interest in the potential roles of extracellular microRNAs (miRNAs) in central nervous system (CNS) pathologies, there has been little research on extracellular miRNAs in early stages of cognitive decline. We leverage the longitudinal Normative Aging Study (NAS) cohort to investigate associations between plasma miRNAs and cognitive function among cognitively normal men.Methods: This study includes data from up to 530 NAS participants (median age: 71.0 years) collected from 1996 to 2013, with a total of 1,331 person-visits (equal to 2,471 years of follow up). Global cognitive function was assessed using the Mini-Mental State Examination (MMSE). Plasma miRNAs were profiled using small RNA sequencing. Associations of expression of 381 miRNAs with current cognitive function and rate of change in cognitive function were assessed using linear regression (N = 457) and linear mixed models (N = 530), respectively.Results: In adjusted models, levels of 2 plasma miRNAs were associated with higher MMSE scores (p < 0.05). Expression of 33 plasma miRNAs was associated with rate of change in MMSE scores over time (p < 0.05). Enriched KEGG pathways for miRNAs associated with concurrent MMSE and MMSE trajectory included Hippo signaling and extracellular matrix-receptor interactions. Gene targets of miRNAs associated with MMSE trajectory were additionally associated with prion diseases and fatty acid biosynthesis.Conclusions: Circulating miRNAs were associated with both cross-sectional cognitive function and rate of change in cognitive function among cognitively normal men. Further research is needed to elucidate the potential functions of these miRNAs in the CNS and investigate relationships with other neurological outcomes.

Effectiveness of Nootropics in Combination with Cholinesterase Inhibitors on Cognitive Function in Mild-to-Moderate Dementia: A Study Using Real-World Data.

The clinical benefits of nootropics in the treatment of cognitive decline has been either limited or controversial. This study aimed to observe the effectiveness of cholinesterase inhibitor (ChEI) and nootropics combination in the treatment of cognitive impairment in dementia. Data were based on electronic medical records in a university health system. Patients with mild-to-moderate dementia and no history of prior cognitive enhancer use were included (n = 583). The subjects were categorized into the ChEI only group and the ChEI and nootropics combination group. The primary outcome measure was the change in cognitive function, as assessed by the mini-mental state examination (MMSE) from baseline to 300–400 days after the first ChEI prescription. Subsequent analyses were conducted in consideration of the dementia type, medical adherence, and type of nootropics. The changes in MMSE scores from baseline to endpoint were not significantly different between the two groups. In Alzheimer’s dementia, the combination group showed significantly less deterioration in MMSE language subscale scores compared to the ChEI only group (F = 6.86, p = 0.009), and the difference was consistent in the highly adherent subjects (F = 10.16, p = 0.002). The choline alfoscerate and the ginkgo biloba extract subgroups in Alzheimer’s dementia showed more significant improvements in the MMSE language subscale scores compared to the other nootropics subgroup (F = 7.04, p = 0.001). The present study showed that the effectiveness of ChEI and nootropics combination on cognition may appear differently according to the dementia type. This emphasizes the need for well-controlled studies to generalize the effectiveness of nootropics across various clinical settings.

Migraine, Cognitive Decline, and Dementia in Older Adults: A Population-Based Study.

The potential impact of migraine on cognitive aging among older adults remains controversial. To examine the relationship of migraine and subtypes with cognitive decline and dementia in an older Swedish population. This population-based study included 3,069 participants (age ≥ 60 years) from the Swedish National study on Aging and Care in Kungsholmen, Stockholm. Baseline examination was conducted in 2001-2004, and participants were followed every 3 or 6 years until 2013-2016. Data were collected through face-to-face interviews, clinical examinations, laboratory tests, and linkage with registers. Global cognitive function was measured with the Mini-Mental State Examination (MMSE). Dementia was diagnosed according to the DSM-IV criteria. Migraine and subtypes were defined following the international classification system. Data were analyzed using logistic regression, Cox regression, and linear mixed-effects models. At baseline, 305 participants were defined with non-migraine headache and 352 with migraine. The cross-sectional analysis showed that the multivariable-adjusted odds ratio (95% confidence interval) of prevalent dementia was 0.49 (0.20-1.21) for migraine and 0.66 (0.26-1.66) for migraine without aura. The longitudinal analysis showed that the multivariable-adjusted hazard ratios of incident dementia associated with migraine and subtypes ranged 0.68-0.89 (p > 0.05). Furthermore, migraine and subtypes were not significantly associated with either baseline MMSE score or MMSE changes during follow-ups (p > 0.05). The nonsignificant associations did not vary substantially by age, APOEɛ4 allele, cerebrovascular disease, and antimigraine treatment (p for interactions > 0.05). This study shows no evidence supporting the associations of migraine and its subtypes with cognitive decline and dementia among older adults.

IMPACT OF SEX AND ANTIHYPERTENSIVE MEDICATION ON GLOBAL COGNITION IN PRIMARY CARE OLDER ADULTS

Objective: The goal of this study is to determine the impact of sex on the effects of different antihypertensive drugs classes, whether in monotherapy or in combination therapy, on the global cognition scores of older adults to identify the most appropriate medication regime in men and women. Design and method: This study used the ESA - Services study, consisting of a sample of 1811 older adults (&gt;65 years) recruited in primary care practices in Quebec-Canada. Participants were examined for the Mini-Mental State Examination (MMSE), at three-time points: baseline, + 3 years, and + 4 years. Participants granted access to their provincial health record to assess: hypertension status, time since diagnosis, list of medications, and ptimisesations. Antihypertensives consumed by participants were divided into six categories: Diuretics, angiotensin II receptor blockers, beta-blockers, calcium channel blockers, angiotensin-converting enzyme inhibitors, and others. We assessed the changes in MMSE scores during the 4-year follow-up on the six antihypertensive groups per sex. Results were adjusted for age, years of education, and the Carlson Comorbidity Index. Results: Women had higher mean MMSE scores than men regardless of their blood pressure status, even though men had more years of formal education (10.65 vs 11.74 years, p &lt; .001). Compared to normotensive individuals, hypertensive women had the highest mean MMSE score at each time point (T1 28.591 (SE .064); T2 28.282 (SE .118); T3 28.524 (SE .119)), while hypertensive men had the worst (T1 28.038 (SE .070); T2 27.694 (SE .125); 27.809 (SE .128)). Women taking angiotensin II receptor antagonists showed the highest MMSE scores (p &lt; .003), and men taking diuretics had the lowest MMSE scores (p &lt; .001) after a 3-year follow-up. Combination therapy of two or three antihypertensives drugs was associated with higher scores in women at T1 and T2 (p &lt; .001). In men, the use of three antihypertensives showed a sharp decrease in MMSE scores from T1 to T3 (p &lt; .001). Conclusions: Sex differences in global cognition outcomes in older adults are related to the type and number of antihypertensive drugs used. Effective antihypertensive treatment should consider the impact of sex to ptimise the effect of pharmacological interventions on cognition.

Diagnostic and prognostic performance to detect Alzheimer’s disease and clinical progression of a novel assay for plasma p-tau217

BackgroundRecent advances in disease-modifying treatments highlight the need for accurately identifying individuals in early Alzheimer’s disease (AD) stages and for monitoring of treatment effects. Plasma measurements of phosphorylated tau (p-tau) are a promising biomarker for AD, but different assays show varying diagnostic and prognostic accuracies. The objective of this study was to determine the clinical performance of a novel plasma p-tau217 (p-tau217) assay, p-tau217+Janssen, and perform a head-to-head comparison to an established assay, plasma p-tau217Lilly, within two independent cohorts.MethodsThe study consisted of two cohorts, cohort 1 (27 controls and 25 individuals with mild-cognitive impairment [MCI]) and cohort 2 including 147 individuals with MCI at baseline who were followed for an average of 4.92 (SD 2.09) years. Receiver operating characteristic analyses were used to assess the performance of both assays to detect amyloid-β status (+/−) in CSF, distinguish MCI from controls, and identify subjects who will convert from MCI to AD dementia. General linear and linear mixed-effects analyses were used to assess the associations between p-tau and baseline, and annual change in Mini-Mental State Examination (MMSE) scores. Spearman correlations were used to assess the associations between the two plasma measures, and Bland-Altmann plots were examined to assess the agreement between the assays.ResultsBoth assays showed similar performance in detecting amyloid-β status in CSF (plasma p-tau217+Janssen AUC = 0.91 vs plasma p-tau217Lilly AUC = 0.89), distinguishing MCI from controls (plasma p-tau217+Janssen AUC = 0.91 vs plasma p-tau217Lilly AUC = 0.91), and predicting future conversion from MCI to AD dementia (plasma p-tau217+Janssen AUC = 0.88 vs p-tau217Lilly AUC = 0.89). Both assays were similarly related to baseline (plasma p-tau217+Janssen rho = −0.39 vs p-tau217Lilly rho = −0.35), and annual change in MMSE scores (plasma p-tau217+Janssenr = −0.45 vs p-tau217Lillyr = −0.41). Correlations between the two plasma measures were rho = 0.69, p < 0.001 in cohort 1 and rho = 0.70, p < 0.001 in cohort 2. Bland-Altmann plots revealed good agreement between plasma p-tau217+Janssen and plasma p-tau217Lilly in both cohorts (cohort 1, 51/52 [98%] within 95%CI; cohort 2, 139/147 [95%] within 95%CI).ConclusionsTaken together, our results indicate good diagnostic and prognostic performance of the plasma p-tau217+Janssen assay, similar to the p-tau217Lilly assay.