Lower Mini-Mental State Examination Scores Research Articles

Superoxide Dismutase Modified the Association of Serum Malondialdehyde Levels with Cognitive Decline Among Older Adults: Findings from the Chinese Longitudinal Healthy Longevity Survey.

Numerous studies have investigated the correlation between malondialdehyde (MDA) and cognitive decline. However, limited research has explored the interplay between superoxide dismutase (SOD), C-reactive protein (CRP), and MDA. This study aims to scrutinize the association between MDA and cognitive function in older adults, while also elucidating the roles of SOD and CRP within this relationship. Utilizing data from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) spanning 2008-2009, 2011-2012, and 2014, this study included 2,696 eligible subjects. Cognitive function was evaluated using the Chinese version of the Mini-Mental State Examination (MMSE). Linear mixed-effects models were employed to examine the links between MDA, SOD, CRP, and their interactions with cognitive function. Elevated serum levels of MDA and CRP, as well as decreased serum SOD levels, were related to decreased cognitive function (β= -0.220 and -0.346, 95% CI: -0.399, -0.041 and -0.526, -0.167 for MDA and CRP; β= 0.384, 95% CI: 0.204, 0.564 for SOD). Notably, a significant interaction between MDA and SOD was detected (p = 0.001). An increase per standard deviation in serum MDA levels was significantly associated with a 0.347-point lower MMSE score only in participants with normal cognitive function and high SOD levels (β= -0.347, 95% CI: -0.497, -0.197; p < 0.001). Elevated serum MDA levels in the normal population with high SOD levels suggested diminished cognitive performance. Combining MDA with SOD could be pivotal in identifying older adults at risk of cognitive decline in clinical settings.

Normal pressure hydrocephalus and cognitive impairment: The gait phenotype matters too.

Idiopathic normal pressure hydrocephalus (iNPH) is a chronic neurological disease resulting in progressive gait and cognitive disorders. We investigated whether the gait phenotype is associated with the severity of cognitive deficits in iNPH. This retrospective study recruited 88 patients (mean age = 76.18 ± 7.21 years, 42% female). Patients were initially referred for suspicion of iNPH and underwent a comprehensive analysis, including gait analysis and cognitive evaluation. In this cohort (27% normal gait, 25% frontal gait, 16% parkinsonian gait, 27% other gait abnormalities), patients with parkinsonian and frontal gait had the lowest Mini-Mental State Examination (MMSE) scores and the slowest gait speed. Patients with normal gait had the highest MMSE scores and gait speed. Frontal gait was associated with lower MMSE score, even after adjusting for age, gender, comorbidities, white matter lesions, and education level (β = -0.221 [95% confidence interval (CI) = -3.718 to -0.150], p = 0.034). Normal gait was associated with the best MMSE scores, even after adjusting for the abovementioned variables (β = 0.231 [95% CI = 0.124-3.639], p = 0.036). Gait phenotypes among iNPH patients are linked to global cognition as assessed with MMSE.

Tracing Neurogenetic Pathways: SIRT1 Gene's Influence on Autism, Alzheimer's, Type II Diabetes, Dementia, and its role in Neurodevelopmental Dynamics

Background: Autism Spectrum Disorder (ASD) encompasses a range of neurodevelopmental conditions characterized by challenges in social interaction, communication, and repetitive behaviors. Concurrent conditions such as Type II Diabetes Mellitus (DM) and dementia are prevalent comorbidities that exacerbate the cognitive impairments associated with ASD. The SIRT1 gene, known for its role in neuroprotection and longevity, has been implicated in the pathophysiology of these disorders. Objective: To determine the expression of the SIRT1 gene in patients with diabetes and dementia and to investigate its potential as a biomarker for cognitive impairment in these populations. Methods: A cohort of 108 diabetic dementia patients and 32 healthy controls were enrolled. SIRT1 expression levels were quantified using chemiluminescent immunoassay (CLIA) and methylation-specific PCR after bisulfite DNA modification. Cognitive function was assessed using the Mini-Mental State Examination (MMSE), and demographic data, along with biochemical parameters such as fasting glucose and HbA1c levels, were analyzed using SPSS version 25. Results: Diabetic dementia patients exhibited significantly lower SIRT1 levels (4.37 ± 1.38 µg/mL) and MMSE scores (12.26 ± 4.56) compared to healthy controls (SIRT1: 11.37 ± 3.64 µg/mL, MMSE: 24.1 ± 3.12). The relative gene expression of SIRT1 in diabetic dementia patients showed a 6.7-fold decrease compared to healthy individuals. Statistical analysis revealed a significant difference in both SIRT1 levels and MMSE scores between the two groups (P&lt;0.05). Conclusion: The underexpression of SIRT1 in diabetic dementia patients and its correlation with lower MMSE scores suggest that SIRT1 could serve as a biomarker for cognitive impairment in this population. The findings advocate for further exploration into SIRT1-targeted interventions, which may improve diagnostics and therapeutic approaches for neurodegenerative conditions associated with ASD.

Comparing the Efficacy of Two Cognitive Screening Tools in Identifying Gray and White Matter Brain Damage among Older Adults.

Ageing is associated with structural changes in brain regions and functional decline in cognitive domains. Noninvasive tools for identifying structural damage in the brains of older adults are relevant for early treatment. This study aims to evaluate and compare the accuracy of the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA©) in identifying gray and white matter brain damage in older individuals with varying degrees of cognitive impairment. Ninety older adults (62 women) with an average age of 69 ± 7 years were enrolled and categorized as having no cognitive impairment (NCI), mild cognitive impairment (MCI), or moderate cognitive impairment (MoCI). Magnetic resonance imaging (MRI) was utilized to assess the number, volume, and distribution of brain damage. The Fazekas and Scheltens scales were applied to the brain MRIs, and inferential statistics were employed to compare variables among the groups. Cognitive impairment was observed in 56.7% of the participants (95% confidence interval (CI): 46.4-66.4%), with thirty-six older adults (40%) classified as MCI and 15 (17%) as MoCI. Cognitive impairment and medial temporal lobe (MTL) atrophy were found to be associated (p=0.001), exhibiting higher mean volume scales of the MTL atrophied area in the MoCI group (p < 0.001). The MMSE accurately revealed MTL atrophy based on the Scheltens (p < 0.05) and Fazekas (p < 0.05) scales. At the same time, the MoCA accurately identified periventricular white matter (PWM) abnormalities according to the Fazekas scale (p < 0.05). The MMSE and MoCA screening tools effectively identified gray and white matter brain damage in older adults with varying degrees of cognitive impairment. Lower MMSE scores are associated with MTL atrophy and lesions, and lower MoCA scores are related to PWM lesions. The concurrent use of MMSE and MoCA is recommended for assessing structural changes in distinct brain regions.

Freezing of gait in idiopathic normal pressure hydrocephalus

BackgroundReports of freezing of gait (FoG) in idiopathic normal pressure hydrocephalus (iNPH) are few and results are variable. This study’s objective was to evaluate the frequency of FoG in a large cohort of iNPH patients, identify FoG-associated factors, and assess FoG’s responsiveness to shunt surgery.MethodsVideotaped standardized gait protocols with iNPH patients pre- and post-shunt surgery (n = 139; median age 75 (71–79) years; 48 women) were evaluated for FoG episodes by two observers (Cohens kappa = 0.9, p < 0.001). FoG episodes were categorized. Mini-mental state examination (MMSE) and MRI white matter hyperintensities (WMH) assessment using the Fazekas scale were performed. CSF was analyzed for Beta-amyloid, Tau, and Phospho-tau. Patients with and without FoG were compared.ResultsTwenty-two patients (16%) displayed FoG at baseline, decreasing to seven (8%) after CSF shunt surgery (p = 0.039). The symptom was most frequently exhibited during turning (n = 16, 73%). Patients displaying FoG were older (77.5 vs. 74.6 years; p = 0.029), had a slower walking speed (0.59 vs. 0.89 m/s; p < 0.001), a lower Tinetti POMA score (6.8 vs. 10.8; p < 0.001), lower MMSE score (21.3 vs. 24.0; p = 0.031), and longer disease duration (4.2 vs. 2.3 years; p < 0.001) compared to patients not displaying FoG. WMH or CSF biomarkers did not differ between the groups.ConclusionsFoG is occurring frequently in iNPH patients and may be considered a typical feature of iNPH. FoG in iNPH was associated with higher age, longer disease duration, worse cognitive function, and a more unstable gait. Shunt surgery seems to improve the symptom.

Neighborhood disadvantage reduces cognitive reserve independent of neuropathologic change.

Individuals in socioeconomically disadvantaged neighborhoods exhibit increased risk for impaired cognitive function. Whether this association relates to the major dementia-related neuropathologies is unknown. This cross-sectional study included 469 autopsy cases from 2011 to 2023. The relationships between neighborhood disadvantage measured by Area Deprivation Index (ADI) percentiles categorized into tertiles, cognition evaluated by the last Mini-Mental State Examination (MMSE) scores before death, and 10 dementia-associated proteinopathies and cerebrovascular disease were assessed using regression analyses. Higher ADI was significantly associated with lower MMSE score. This was mitigated by increasing years of education. ADI was not associated with an increase in dementia-associated neuropathologic change. Moreover, the significant association between ADI and cognition remained even after controlling for changes in major dementia-associated proteinopathies or cerebrovascular disease. Neighborhood disadvantage appears to be associated with decreased cognitive reserve. This association is modified by education but is independent of the major dementia-associated neuropathologies.

Impact of frailty severity and severe pain on cognitive function for community-dwelling older adults with arthritis: a cross-sectional study in Korea

Pain is a major symptom of arthritis in older adults, often leading to frailty and cognitive decline. However, few studies have investigated the relationship among pain, frailty, and cognitive function in older adults with arthritis. This study aimed to investigate the factors influencing cognitive function and the impact of frailty severity and pain on cognitive function in older adults with arthritis using a Korean population-based dataset. This cross-sectional descriptive study involved the secondary data of 1089 participants from the seventh and eighth waves of the Korean Longitudinal Study on Aging. We examined general characteristics, health behaviors, health conditions (including severe pain and frailty), and cognitive function. Participants were categorized based on the presence or absence of pain severity and frailty status as follows: robust, only severe pain, only prefrail, prefrail with severe pain, only frail, and frail with severe pain. Multiple linear regression analysis was performed to establish correlations between groups and cognitive function. The only-prefrail group was the largest (19.7%) among participants experiencing either pain or frailty. Advanced age, sex, level of education, and visual and hearing impairments were significantly associated with cognitive function. Compared to the robust group, only prefrail (β = -1.54, confidence interval [CI] = − 2.33; − 0.76), prefrail with severe pain (β = − 2.69, CI = − 3.52; − 1.87), only frail (β = − 4.02, CI = − 5.08; − 2.97), and frail with severe pain (β = − 5.03, CI = − 5.99; − 4.08) groups were associated with lower Mini-Mental State Examination scores. The study confirmed that severe pain alone does not significantly impact cognitive function in older adults with arthritis. To prevent cognitive decline in this group, assessment of both pain and frailty severity is essential to predict high-risk groups and provide appropriate interventions, such as transfer to hospitals or primary clinics according to the severity of pain and frailty.

Hippocampal ΔFosB expression is associated with cognitive impairment in a subgroup of patients with childhood epilepsies.

Epilepsy is a chronic neurological disorder characterized by recurrent seizures, and is often comorbid with other neurological and neurodegenerative diseases, such as Alzheimer's disease (AD). Patients with recurrent seizures often present with cognitive impairment. However, it is unclear how seizures, even when infrequent, produce long-lasting deficits in cognition. One mechanism may be seizure-induced expression of ΔFosB, a long-lived transcription factor that persistently regulates expression of plasticity-related genes and drives cognitive dysfunction. We previously found that, compared with cognitively-intact subjects, the activity-dependent expression of ΔFosB in the hippocampal dentate gyrus (DG) was increased in individuals with mild cognitive impairment (MCI) and in individuals with AD. In MCI patients, higher ΔFosB expression corresponded to lower Mini-Mental State Examination scores. Surgically resected DG tissue from patients with temporal lobe epilepsy also showed robust ΔFosB expression; however, it is unclear whether ΔFosB expression also corresponds to cognitive dysfunction in non-AD-related epilepsy. To test whether DG ΔFosB expression is indicative of cognitive impairment in epilepsies with different etiologies, we assessed ΔFosB expression in surgically-resected hippocampal tissue from 33 patients with childhood epilepsies who had undergone Wechsler Intelligence Scale for Children (WISC) testing prior to surgery. We found that ΔFosB expression is inversely correlated with Full-Scale Intelligence Quotient (FSIQ) in patients with mild to severe intellectual disability (FSIQ < 85). Our data indicate that ΔFosB expression corresponds to cognitive impairment in epilepsies with different etiologies, supporting the hypothesis that ΔFosB may epigenetically regulate gene expression and impair cognition across a wide range of epilepsy syndromes.

COGNITIVE AND FUNCTIONAL IMPACTS OF CHILD LABOR IN INDIA: THE MEDIATING ROLE OF EDUCATION

Abstract This study aims to examine how entry into the labor market in childhood is associated with deficits in late-life cognitive and functional health. Using the Cumulative Advantage/Disadvantage Theory, it further explores how educational attainment, an indicator of socio-economic status, mediates the associations between child labor and cognitive and functional health among older adults in India. Lastly, it investigates if the results vary by gender. We use the nationally representative World Health Organization Study on global AGEing and Health (SAGE), and select respondents aged 50 years or older (n = 6,215 for Mini-Mental State Examination (MMSE); n=6,408 for the Functional Limitation (FL)). Mediation models were performed for each dependent variable using the sgmediation2 program, bootstrapped 5,000 resamples, and percentile bootstrap confidence interval. The indirect and total effects of child labor on MMSE were significant, while the direct effect of child labor was not. For FL, the indirect effect was significant, but the direct and total effects were not. Gender difference was found in terms of the direct effect, child work was directly associated with a lower MMSE score in older women (p &amp;lt; .01), whereas it was not significant for older men. Findings suggest that early entry into the labor market (as a child) has a negative impact on older adults’ MMSE and FL through deprivation of educational opportunities. Providing opportunities for completing certain level of education can mitigate the negative impact of child labor on health in old age.

THE ASSOCIATION OF A NOVEL PHYSICAL ACTIVITY METRIC WITH COGNITION AND RISK OF DEMENTIA

Abstract Physical activity (PA) is associated with cognitive function and Alzheimer’s disease and related dementias (ADRD). Although associations between continuously measured PA and ADRD have been assessed, multiscale entropy (MSE), which quantifies dynamics of physiological systems over multiple time scales, has not been used to quantify daily activity rhythms in older adults by cognitive status. We examined the association of this novel metric of PA complexity with cognitive function, mild cognitive impairment (MCI), and dementia in participants of the Baltimore Longitudinal Study of Aging. A total of 615 older adults (mean age=73.9±11.3 years, 54.5% women) completed a 7-day wrist-worn accelerometer assessment between 2015-2019. Global cognitive function was measured using the Mini-Mental State Examination (MMSE). Mild cognitive impairment (MCI) or dementia was diagnosed based on Petersen criteria and Diagnostic and Statistical Manual of Mental Disorders, respectively. Unadjusted logistic regression models showed that participants in the lowest tertile of complexity had 2.31 times the odds of low MMSE score (≤26) compared to those in the highest tertile (odds ratio [OR]=2.31, 95% confidence interval [CI]=1.09-4.89). This association lost significance after adjusting for age, sex, race, and education years. The lowest tertile of complexity was also associated with 2.58 times the odds of MCI/dementia diagnosis, adjusting for demographics (OR=2.58, 95% CI=1.06-6.31). These results suggest that lower complexity of accelerometry-detected movement is associated with poorer cognitive function and greater risk of MCI/dementia. Future longitudinal studies are warranted to examine whether altered complexity of daily activity rhythms may act as a preclinical indicator of ADRD.

RISK AND PROTECTIVE FACTORS OF COGNITIVE FUNCTIONING AND DEMENTIA: COMPARING MEXICAN AND NON-MEXICAN HISPANICS

Abstract This study investigates the cognitive functioning of Hispanic individuals aged 65 and above, focusing on the unique risk and protective factors associated with dementia in Mexican Hispanics and non-Mexican Hispanics. The study utilizes data from the Harmonized Cognitive Assessment Protocol (HCAP) subsample of the Health and Retirement Study (HRS), comprising 388 Hispanic older individuals who participated in the HCAP in 2016 (traced back to 2000), allowing for a comprehensive examination of cognitive health within this population. Cognitive function was measured using the Mini-Mental State Examination (MMSE) score and to classify dementia. The findings reveal distinct patterns in cognitive functioning between Mexican Hispanic and non-Mexican Hispanic populations. Mexican Hispanic males exhibit lower MMSE scores across all age groups, while Mexican Hispanic females show slightly higher scores compared to non-Mexican Hispanic females. Education and wealth levels do not significantly affect cognitive scores in either group. Mexican Hispanics have lower odds of dementia compared to non-Mexican Hispanics, even when accounting for sociodemographic, midlife, and late-life characteristics. Both educational attainment and wealth emerge as protective factors against dementia for both groups. Additionally, midlife obesity, hearing loss, and later-life physical inactivity are identified as specific risk factors for dementia in Mexican Hispanics but have an insignificant impact on non-Mexican Hispanics. These findings have implications for targeted interventions and policies to promote cognitive well-being and address health disparities in older Hispanics. The aim is to improve the overall quality of life and achieve equitable healthcare outcomes.

Determinants of Cognitive Trajectories in Lower Educated Older Adults: Evidence from Brazil.

AbstractBackgroundPatterns of cognitive change and modifiable factors for declining versus stable cognitive trajectories have rarely been described in a lower‐educated older population. Our goal was to identify heterogeneous long‐term trajectories of cognitive functioning and explore possible factors associated with cognitive decline beyond education, among older Brazilian adults.MethodWe used data on n = 1,042 adults aged ≥ 60 from the Health, Welfare and Aging (SABE) without cognitive impairment at baseline over four waves (2000‐2015) in São Paulo, Brazil. We applied group‐based trajectory modelling to identify cognitive trajectories. Cognition was measured using the abbreviated version of the Mini‐Mental State Examination (MMSE).ResultWe identified three cognitive groups: stable (n = 754), mild declining (n = 183), and strongly declining (n = 105). The probability of being in the strongly declining group membership was 10.7%. According to the MMSE classification, the mild declining group reached the average threshold for cognitive impairment on the last follow‐up, while the strongly declining group was on the second follow‐up. Furthermore, respondents in the stable trajectory were more likely to report more than primary education, to be white and married, to earn more than four times the minimum wage/month, to live in urban areas during childhood, and to practice vigorous physical activity at least three times a week. On the other hand, those in the strongly declining trajectory were more likely to identify as black or mixed, to self‐report subjective emptiness, and to have lower BMI, diabetes, and stroke. Moreover, both mild and strongly declining participants presented higher average age and lower MMSE scores at baseline compared to the stable trajectory. The multinomial logistic regression analysis revealed that respondents who self‐reported being mixed, had higher age, had primary education, had a stroke, and smoked at baseline were more likely to be in the strongly declining group.ConclusionOur findings suggest that besides education, interventions to reduce cognitive decline might include health and social policies addressing inequalities and modifiable risk factor burdens to improve later‐life cognitive functioning of at‐risk individuals. Sample attrition suggests estimates of the magnitude of the risk factors for cognitive decline to be conservative.

Anosognosia is associated with increased prevalence and faster development of neuropsychiatric symptoms in Mild Cognitive Impairment

AbstractBackgroundBoth the loss of awareness for cognitive decline (a.k.a anosognosia) and neuropsychiatric symptoms (NPS) are commonly seen in patients with Alzheimer’s disease (AD) dementia, even in the prodromal stages. Anosognosia and NPS may negatively affect caregiver burden and patient’s activities of daily living. Despite the high impact of these symptoms on patients and their caregivers, our knowledge of how they develop across the AD spectrum is limited. Here, we explored the cross‐sectional and longitudinal associations between anosognosia and NPS in individuals with mild cognitive impairment (MCI).MethodWe included 310 participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) with a baseline Clinical Dementia Rating global score of 0.5. Everyday Cognition (ECog) questionnaire scores were used to measure complaints from participants and study‐partners at baseline and annually over a mean of 4 years (SD = 3). Anosognosia was defined as the study‐partner having an ECog score ≥2.5/4 and the participant having an ECog score ≤2.5/4 on their baseline measure and their last observation and without having more than 2 consecutive deviating observations during the follow‐up period. The 12 study‐partner‐rated Neuropsychiatric Inventory items determined the presence or absence of specific NPS (see Table 1). The Mini‐Mental State Examination (MMSE), an assessment used to screen for cognitive impairment, was administered annually. Survival analyses were performed to analyze the rate of appearance of NPS over time in individuals with and without anosognosia.ResultSixty participants displayed anosognosia, while 250 did not. At baseline, groups had similar lengths of follow‐up. Participants with anosognosia had lower MMSE scores and a higher proportion of amyloid positivity (see Table 1). At baseline, the frequency of agitation and disinhibition was higher in the anosognosia group. Survival analyses showed earlier onset of all NPS in the anosognosia group (see Figure 1). Specifically, aberrant motor behavior, irritability, disinhibition, apathy, agitation, and hallucinations were highly significant.ConclusionLoss of awareness for cognitive decline is associated with greater frequency and faster onset of NPS over time in participants with MCI. These results support the hypothesis of a potential common underlying neurophysiological process, a finding that needs to be addressed further in future studies.

Speech changes in neurodegenerative diseases relate to clinical outcomes

AbstractBackgroundThe detection and characterization of speech changes may help in the identification of neurodegenerative diseases and have the potential to help with patient characterization and monitoring. Yet, there is limited research validating the presence of speech changes across different types of neurodegenerative disease. We report on the relationships between speech and other clinical assessments in the individuals with different dementia diagnoses and in comparison to healthy older adults.MethodWe analyzed speech recordings from 109 patients (52F, 57M; Age = 72.63± 8.61) who were diagnosed with various neurodegenerative diseases, including Alzheimer’s disease, Frontotemporal Dementia, and Vascular Cognitive Impairment, in a cognitive neurology memory clinic. Speech recordings of an open‐ended picture description task were processed using the Winterlight speech analysis platform which generates &gt;500 acoustic and linguistic features. We investigated the linear relationship between the speech features and clinical assessments including the Mini Mental State Examination (MMSE), Western Aphasia Battery (WAB), and Mattis Dementia Rating Scale while controlling for age, sex and years of education. Speech features that were significantly associated with clinical measures were then included in group comparisons with healthy older adults (N = 74, ∼39F; Age = 61.31±7.29).ResultSpeech features including lexical and syntactic features were significantly correlated with clinical assessments in patients, across diagnoses. Lower MMSE scores were associated with the use of more familiar nouns (β = ‐1.60, p&lt;.001). Similarly, increased impairment as assessed by the WAB was correlated with the use of higher frequency nouns (β = ‐0.01, p&lt;.001). Patients used significantly more nouns (z = 6.25, p&lt;.001) and shorter words (z = 8.33, p&lt;.001) than the healthy older adults. Their speech duration was also significantly shorter (z = 7.98, p&lt;.001) and they paused more (z = 5.19, p&lt;.001).ConclusionSpeech changes representing decreased speech, with simpler vocabularies and syntax, were detectable in patients with different neurodegenerative diseases and correlated with clinical outcomes. These same speech patterns differed in patients with neurodegenerative disease compared to healthy older adults. Speech has the potential to be a sensitive measure for detecting cognitive impairments across various neurodegenerative diseases.

Associations of oral health status and swallowing function with cognitive impairment in the aging population: a cross-sectional study

BackgroundThe purpose of this study was to investigate the relationships of oral health status and swallowing function with cognitive impairment in community-dwelling older adults from Changsha, Hunan Province, China.MethodsIn this cross-sectional study, we analyzed the data of 215 participants aged ≥ 50 years which were retrieved from the Xiangya and Panasonic mild cognitive impairment (MCI) Study, a community-based study conducted among the residents of the urban areas of Hunan province in China. Demographic information of all participants was collected. We determined oral function by evaluating oral hygiene, oral dryness, occlusal force, tongue pressure, chewing function, swallowing function, remaining teeth number, and other indicators. The mini-mental state examination (MMSE) was used to screen for cognitive function. The relationship between each oral function evaluation item and cognitive function was investigated using correlation analysis. The associations between oral health status and swallowing function with cognitive impairment were inferred using multiple regression analysis.ResultsThe general characteristics of participants showed statistically significant correlation coefficients in number of teeth remaining (p = 0.003) and number of teeth lost (p < 0.0001). Almost half of the 25 participants (48%) were aged from 70–80 years. Only 25 older adults (11.6% of the participants) were determined to have cognitive impairment by MMSE sores less than 24. Tongue pressure in male participants was the only significant independent variable that was associated with cognitive impairment (p = 0.01971). The results indicate that male participants with lower MMSE scores had a relative deficiency in tongue pressure.ConclusionsIn this cross-sectional study, the oral health status and swallowing function of participants were in relatively good condition and showed low correlations with cognitive impairment. However, lower tongue pressures were associated with lower MMSE scores in males, indicating it could serve as a novel oral function index for evaluating cognitive impairment.

Gender-specific linkages: frailty, polypharmacy, anti-cholinergic burden, and 5-year mortality risk-a real-world analysis.

With higher age, frailty escalates the risk of falls, unexpected physical dysfunction, hospitalization, and mortality. Polypharmacy in the older population is a major challenge that not only increases medical costs, but also may worsen the risk of hospitalization and death. More importantly, the properties of anti-cholinergic drugs contribute various negative effects. This study aimed to investigate the sex difference in the association of polypharmacy, anticholinergic burden, and frailty with mortality. Participants older than 65 years who attended the geriatric outpatient clinic of the study center between January 2015 and July 2020 were invited to participate in this retrospective study. Comprehensive geriatric assessment data were collected and the phenotype of frailty was determined by Fried's criteria. Cox regression and the Kaplan-Meier curve were used to identify risk factors of 5-year survival along with intergroup differences in the risks. Of the 2,077 participants, 47.5% were female. The prevalence of frailty and the rate of polypharmacy were 44.7% and 60.6%, respectively. Higher age, male sex, low body mass index, low Mini-Mental State Examination scores, low activities of daily living, frailty status, polypharmacy, and a high Charlson Comorbidity Index score, and greater anticholinergic burden were significant risk factors that were associated with the 5-year all-cause mortality. Male patients with frailty exhibited the highest risks of mortality compared with male patients without frailty and female patients with or without frailty. Polypharmacy was significantly associated with a higher 5-year mortality rate in the frail male group compared with the non-frail male. In frail female group, individuals with a higher anticholinergic burden (as indicated by the Anticholinergic Cognitive Burden Scale) from drug usage exhibited an elevated 5-year mortality rate. Polypharmacy and greater anticholinergic burden, synergistically interacted with frailty and intensified the 5-year mortality risk in a gender-specific manner. To mitigate mortality risks, clinicians should prudently identify polypharmacy and anticholinergic burden in the older population.

Contribution of the APOE Genotype to Cognitive Impairment in Individuals With NOTCH3 Cysteine-Altering Variants.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most prevalent monogenic cerebral small-vessel disease. Phenotype variability in CADASIL suggests the possible role of genetic modifiers. We aimed to investigate the contributions of the APOE genotype and Neurogenic locus notch homolog protein 3 (NOTCH3) variant position to cognitive impairment associated with CADASIL. Patients with the cysteine-altering NOTCH3 variant were enrolled in a cross-sectional study, including the Mini-Mental State Examination (MMSE), brain magnetic resonance imaging, and APOE genotyping. Cognitive impairment was defined as an MMSE score <24. The associations between the MMSE score and genetic factors were assessed using linear regression models. Bayesian adjustment for confounding was used to identify clinical confounders. A total of 246 individuals were enrolled, among whom 210 (85%) harbored the p.R544C variant, 96 (39%) had cognitive impairment, and 150 (61%) had a history of stroke. The APOE ɛ2 allele was associated with a lower MMSE score (adjusted B, -4.090 [95% CI, -6.708 to -1.473]; P=0.023), whereas the NOTCH3 p.R544C variant was associated with a higher MMSE score (adjusted B, 2.854 [95% CI, 0.603-5.105]; P=0.0132) after adjustment for age, education, and history of ischemic stroke. Mediation analysis suggests that the associations between the APOE ɛ2 allele and MMSE score and between the NOTCH3 p.R544C variant and MMSE score are mediated by mesial temporal atrophy and white matter hyperintensity, respectively. APOE genotype may modify cognitive impairment in CADASIL, whereby individuals carrying the APOE ɛ2 allele may present a more severe cognitive impairment.

18 Automatically calculated lexical and sentential context features of connected speech predict cognitive impairment

Objective:Early detection is critical to the effective management of Alzheimer’s Disease (AD) and other forms of dementia. Existing screening assessments are often costly, require substantial expertise to administer, and may be insensitive to mild changes in cognition. A promising alternative is automatically measuring features of connected speech (c.f., Ostrand &amp; Gunstad, 2021, Journal Geriatric Psych &amp; Neurol) to predict impairment. Here, we built on prior work examining how well speech features predicted cognitive impairment. Unique to the current work, we attempted to capture more holistic effects of cognitive impairment by examining the relevance of linguistic features that measure sentential or discourse context properties of speech, including the context in which filler words (e.g., um) occur, and the predictability of individual words within their sentence context, computed from a large computational language model (GPT-2).Participants and Methods:Participants completed the Cookie Theft picture description task, with data available in the DementiaBank corpus (Becker et al., 1994, Arch Neurol). Descriptions that contained at least 50 words (N = 214) were submitted to an automatic feature calculation pipeline written in Python to calculate various part-of-speech counts, lexical diversity metrics, and mean lexical frequency, as well as multiple metrics related to lexical surprisal (i.e., how surprising a word is given its context).Surprisal of individual words was computed using the pre-trained GPT-2 transformer language model (Radford et al., 2019, Comput. Sci.) by computing word probability given the previous 12 words. Multiple linear regression was performed using 17 linguistic features jointly as predictors, and Mini-Mental State Examination (MMSE) score as the outcome variable. Simple regressions were calculated between each feature and MMSE scores to examine the predictability of each linguistic feature on cognitive decline.Results:A multiple linear regression model containing all linguistic features plus demographic information (age, sex, education) significantly predicted MMSE scores (Adjusted R2 = 0.41, F20, 193 = 8.37, p &lt; .001), and explained significantly more variance in MMSE scores than did demographic variables alone (F17193 = 6.85, p &lt; .001). Individual predictors that were significantly correlated with MMSE score included: how unexpected an individual’s word choices were, given the preceding context (median surprisal: r = -0.33, p &lt; 0.001; interquartile range: r = 0.18, p &lt; 0.02), mean lexical frequency (r = -0.50, p &lt; .001), and usage of definite articles (r = 0.31, p &lt; 0.001), nouns (r = 0.26, p &lt; .001), and empty words (r = -0.25, p &lt; 0.001).Conclusions:Participants with lower MMSE scores, indicating greater impairment, used more frequent, yet more surprising, words, and produced more empty words and fewer definite articles and nouns. These results suggest that measures of semantic specificity and coherence of speech could be meaningful predictors of cognitive decline, and can be computed automatically from speech transcriptions. The results also provide novel evidence that computational approaches to estimating lexical predictability may have value in predicting the degree of decline, motivating future work in other speech elicitation tasks and differing clinical groups.

52 Memory Learning Curve and in vivo Brain Pathology in Non-Demented Individuals with Autosomal Dominant Alzheimer’s Disease: Findings from the Colombia-Boston Biomarker Study

Objective:Associative memory is impacted early in Alzheimer’s disease (AD). Poorer performance on associative memory tests has been related to greater amyloid and regional tau burden in preclinical AD. Our group previously examined the association of brain pathology and performance on the Free and Cued Selective Reminding Test (FCSRT) in Autosomal Dominant Alzheimer’s Disease (ADAD), finding that associative memory summary scores distinguished non-demented mutation carriers from non-carriers several years before clinical onset of cognitive impairment. In the current study, we examined whether FCSRT learning slopes were associated with brain pathology in a sample of ADAD carriers and non-carriers.Participants and Methods:There were 119 participants including 57 non-demented carriers of the Colombian kindred with the Presenilin1 E280A mutation and 62 non-carrier family members (mean age= 36.3, 60% female). Participants were administered the Mini-Mental State Examination (MMSE), a measure of global cognitive status, and the FCSRT, which consists of three trials in which participants are asked to freely recall the same list of 16 items. It is a well-established measure known to be sensitive to early changes in AD. A subsample of 69 participants (32 carriers and 37 non-carriers) underwent positron emission tomography (PET) to measure in vivo cortical amyloid-beta (Pittsburgh compound B, PiB), and regional tau (Flortaucipir, FTP) burden in entorhinal and precuneus regions, which are among the earliest sites of tau accumulation in this ADAD population. Mann Whitney U tests, Spearman correlations, and chi-square tests were used to examine group differences and relations among variables of interest. Learning slope was calculated by subtracting the number of items freely recalled in FCSRT Trial 1 from the number of items freely recalled in Trial 3.Results:Compared to non-carriers, carriers had greater cortical amyloid-ß and regional tau burden, lower MMSE scores (mean [SD]: carriers= 27.5 [2.7]; non-carriers= 28.8 [1.0]), and lower scores on total immediate/ delayed free/ cued recall scores on the FCSRT (all p&lt;.01). The groups did not differ on age, sex, or education level (all p&gt; 0.05). In the whole sample and in carriers only, we found that higher MMSE scores were associated with higher learning slope, meaning faster learning (whole group p= 0.25, p= 0.006; carriers p= 0.30, p=0.029). In the whole sample, we found that lower learning slope was associated with higher levels of amyloid (p=-.34, p=.006) and tau in the left, right, and bilateral precuneus region (p=-.43, p&lt;.001; p=-.46, p&lt;.001; p=-.45, p&lt;.001). In carriers only, lower learning slope was associated with higher tau burden in the left, right, and bilateral precuneus specifically (p=-.43, p=.017; p=-.48, p=.008; p=-.46, p=.010, respectively). No significant associations were found in non-carriers.Conclusions:These findings suggest that learning curves on an associative memory test may be sensitive to preclinical pathological changes in AD, specifically within the precuneus, a brain region known to be involved in cue reactivity, episodic memory retrieval, and mental imagery strategies. Future studies with larger samples are warranted to further examine associations between the FCSRT learning curves and regional tau accumulation in individuals with ADAD.

Association between metals and metalloids with cognitive status in Mild Cognitive Impairment subjects

Abstract Mild Cognitive Impairment (MCI) is regarded as a transitional state between normal aging and dementia. Several risk factors have been related to MCI and dementia vulnerability. Among these, metals and metalloids have been hypothesized to affect dementia risk. Our objective was to study the associations between metals and metalloids (cadmium, copper, iron, manganese, selenium, zinc) concentrations in serum and cerebrospinal fluid (CSF) with cognitive impairment status of MCI subjects. 144 individuals newly diagnosed with MCI were recruited at Neurology Memory Clinics at Modena and Reggio Emilia Hospitals (Italy) in the period 2019-2022. The concentrations of elements in paired serum/CSF were determined using inductively coupled plasma mass spectrometry. Participants’ global cognitive status was assessed using the Mini-Mental State Examination (MMSE). Muti-adjusted spline regression analyses were performed to assess the relation between the serum/CSF concentrations and MMSE. Median serum and CSF concentrations were generally higher in men than women, except copper in serum and iron in CSF demonstrating higher concentrations in women. A positive linear association emerged between serum iron concentrations and MMSE, while a slight negative one emerged for serum selenium levels. Cadmium in serum was positively associated with MMSE until 0.2 µg/L and then the association became null, while in CSF a U-shaped relation emerged. A U-shaped relation was also observed for serum copper and CSF iron and manganese levels. CSF selenium concentrations were inversely related to MMSE, although above 5 µg/L the curve flattened. Zinc exhibited the same pattern of association in both serum and CSF, i.e., an inverted U-shaped one. These findings suggest that CSF and serum content of the investigated elements may be differently related with global cognitive status in MCI subjects. Higher levels of selenium and zinc, in particular, are associated with lower MMSE score. Key messages • Heavy metals and metalloids display different pattern of association with global cognitive status. • High levels of selenium and zinc are inversely related with global cognitive status in MCI subjects.