Lower Mini-Mental State Examination Scores Research Articles

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.

Clinical Manifestations.

The 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. We 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 >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). Speech 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<.001). Similarly, increased impairment as assessed by the WAB was correlated with the use of higher frequency nouns (β = -0.01, p<.001). Patients used significantly more nouns (z = 6.25, p<.001) and shorter words (z = 8.33, p<.001) than the healthy older adults. Their speech duration was also significantly shorter (z = 7.98, p<.001) and they paused more (z = 5.19, p<.001). Speech 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.

Excessive Sedentary Time Is Associated with Cognitive Decline in Older Patients with Minor Ischemic Stroke.

Cognitive impairment is commonly seen after acute ischemic stroke (AIS). Sedentary behaviors increase the risk of dementia among community dwelling population. This study aims to investigate the association of sedentary behaviors with poststroke cognitive impairment among older adults of minor AIS. This cohort study recruited 594 older subjects with minor AIS from three hospitals in China during February 1, 2016, and December 31, 2018. Participants were followed up for two years and the sedentary time per day was self-reported at the endpoint of follow-up. Cognitive functions were assessed by Mini-Mental State Examination (MMSE). Participants were categorized into the high and low sedentary time group according to the median sedentary time of the participants. At two years of follow-up, the long sedentary time group had significantly lower MMSE scores than the short sedentary time group [median, (95% CI): 21 (18 to 25) versus 22 (18 to 25), p = 0.368]. The long sedentary time group had a higher speed of cognitive decline than the short sedentary time group. Excessive sedentary time was associated with a higher risk of longitudinal cognitive decline (OR: 2.267, 95% CI: 1.594 to 3.225), adjusting for age, sex, education, body mass index, APOE genotype, comorbidities, symptoms of depression, anxiety, and insomnia, baseline MMSE scores and National Institute of Health Stroke Scale scores, cognitive therapy, and TOAST ischemic stroke subtypes. This study identified a possible link between sedentary behaviors and longitudinal cognitive decline among older patients with minor AIS, suggesting that reducing sedentary time might be helpful for preventing poststroke dementia.

Role of Visual Acuity &amp; Contrast Sensitivity in Early Diagnosis of Cognitive Impairment in Parkinson’s Disease

The study aims to evaluate the role of visual acuity and contrast sensitivity in early diagnosis of cognitive impairment in Parkinson’s disease. This cross sectional study was performed us- ing validated assessments on cognitive function using Mini Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). Visual acuity was assessed using LogMAR and contrast sensitivity using the Pelli-Robson test. Anxiety and depression were assessed using the Hospital Anxiety and Depression Scale (HADS). One hundred patients presenting to the Neurology department for complaints satisfying the criteria for Parkinson’s disease at Saveetha Medical College and Hospital were randomly selected. The visual acuity and contrast sensitivity was found to be decreased in patients with low MMSE and MoCA scores, suggestive of visual function being a marker for progression of cognitive impairment in Parkinson’s disease. This could thereby be used in early diagnosis of dementia and in for- mulating a customised treatment plan for each individual. Parkinson’s disease has a deleteri- ous effect on various aspects of a person’s life, not just the motor functions. This in turn harms the day to day activities of the individuals, mainly the older age group and results in psychological disorders, like anxiety and depression. Therefore, this study aims to establish visual function as a marker for cognitive impairment in Parkinson’s disease, with the hopes of improving the quality of life of patients with this disease, thus revamping their purpose and outlook of their lives.

Spatiotemporal Characteristics of Regional Brain Perfusion Associated with Neuropsychiatric Symptoms in Patients with Alzheimer's Disease.

Current technology for exploring neuroimaging markers and neural circuits of neuropsychiatric symptoms (NPS) in patients with Alzheimer's disease (AD) is expensive and usually invasive, limiting its use in clinical practice. To investigate the cerebral morphology and perfusion characteristics of NPS and identify the spatiotemporal perfusion circuits of NPS sub-symptoms. This nested case-control study included 102 AD patients with NPS and 51 age- and sex-matched AD patients without NPS. Gray matter volume, cerebral blood flow (CBF), and arterial transit time (ATT) were measured and generated using time-encoded 7-delay pseudo-continuous arterial spin labeling (pCASL). Multiple conditional logistic regression analysis was used to identify neuroimaging markers of NPS. The associations between the CBF or ATT of affected brain areas and NPS sub-symptoms were evaluated after adjusting for confounding factors. The neural circuits of sub-symptoms were identified based on spatiotemporal perfusion sequencing. Lower Mini-Mental State Examination scores (p < 0.001), higher Caregiver Burden Inventory scores (p < 0.001), and higher CBF (p = 0.001) and ATT values (p < 0.003) of the right anteroventral thalamic nucleus (ATN) were risk factors for NPS in patients with AD. Six spatiotemporal perfusion circuits were found from 12 sub-symptoms, including the anterior cingulate gyri-temporal pole/subcortical thalamus-cerebellum circuit, insula-limbic-cortex circuit, subcortical thalamus-temporal pole-cortex circuit, subcortical thalamus-cerebellum circuit, frontal cortex-cerebellum-occipital cortex circuit, and subcortical thalamus-hippocampus-dorsal raphe nucleus circuit. Prolonged ATT and increased CBF of the right ATN may be neuroimaging markers for detecting NPS in patients with AD. Time-encoded pCASL could be a reliable technique to explore the neural perfusional circuits of NPS.

Head-to-head comparison between plasma p-tau217 and flortaucipir-PET in amyloid-positive patients with cognitive impairment

BackgroundPlasma phosphorylated tau (p-tau) has emerged as a promising biomarker for Alzheimer’s disease (AD). Studies have reported strong associations between p-tau and tau-PET that are mainly driven by differences between amyloid-positive and amyloid-negative patients. However, the relationship between p-tau and tau-PET is less characterized within cognitively impaired patients with a biomarker-supported diagnosis of AD. We conducted a head-to-head comparison between plasma p-tau217 and tau-PET in patients at the clinical stage of AD and further assessed their relationships with demographic, clinical, and biomarker variables.MethodsWe retrospectively included 87 amyloid-positive patients diagnosed with MCI or dementia due to AD who underwent structural MRI, amyloid-PET (11C-PIB), tau-PET (18F-flortaucipir, FTP), and blood draw assessments within 1 year (age = 66 ± 10, 48% female). Amyloid-PET was quantified in Centiloids (CL) while cortical tau-PET binding was measured using standardized uptake value ratios (SUVRs) referenced against inferior cerebellar cortex. Plasma p-tau217 concentrations were measured using an electrochemiluminescence-based assay on the Meso Scale Discovery platform. MRI-derived cortical volume was quantified with FreeSurfer. Mini-Mental State Examination (MMSE) scores were available at baseline (n = 85) and follow-up visits (n = 28; 1.5 ± 0.7 years).ResultsPlasma p-tau217 and cortical FTP-SUVR were correlated (r = 0.61, p < .001), especially in temporo-parietal and dorsolateral frontal cortices. Both higher p-tau217 and FTP-SUVR values were associated with younger age, female sex, and lower cortical volume, but not with APOE-ε4 carriership. PIB-PET Centiloids were weakly correlated with FTP-SUVR (r = 0.26, p = 0.02), but not with p-tau217 (r = 0.10, p = 0.36). Regional PET-plasma associations varied with amyloid burden, with p-tau217 being more strongly associated with tau-PET in temporal cortex among patients with moderate amyloid-PET burden, and with tau-PET in primary cortices among patients with high amyloid-PET burden. Higher p-tau217 and FTP-SUVR values were independently associated with lower MMSE scores cross-sectionally, while only baseline FTP-SUVR predicted longitudinal MMSE decline when both biomarkers were included in the same model.ConclusionPlasma p-tau217 and tau-PET are strongly correlated in amyloid-PET-positive patients with MCI or dementia due to AD, and they exhibited comparable patterns of associations with demographic variables and with markers of downstream neurodegeneration.

Serum retinol-binding protein 4 in stroke patients: correlation with T helper 17/regulatory T cell imbalance and 3-year cognitive function decline.

Retinol-binding protein 4 (RBP4) promotes atherosclerotic progression and neuronal loss, whereas its association with cognitive impairment in stroke is unclear. Hence, this prospective study aimed to explore the association of serum RBP4 with the T helper (Th)17/regulatory T (Treg) cell ratio and its correlation with cognitive impairment in stroke patients. Peripheral blood samples from 265 stroke patients and 50 healthy controls (HCs) were collected at enrollment for serum RBP4 (by enzyme-linked immunosorbent assay) and Th17 and Treg cells (by flow cytometry) determination. Additionally, stroke patients underwent routine follow-ups, and their Mini-Mental State Examination (MMSE) scores were assessed at baseline and in years 1, 2, and 3 after enrollment. Serum RBP4 was elevated in stroke patients compared to HCs (p < 0.001), with a good ability to differentiate stroke patients from HCs (area under the curve: 0.815). Serum RBP4 was positively associated with Th17 cells (p < 0.001) and the Th17/Treg cell ratio (p < 0.001) and negatively associated with Treg cells (p = 0.003) in stroke patients, whereas it was only positively associated with the Th17/Treg cell ratio (p = 0.027) but not with Th17 (p = 0.075) or Treg (p = 0.130) cells in HCs. Furthermore, increased serum RBP4 was associated with a lower MMSE score (p < 0.001) and a lower incidence of cognition impairment (p = 0.005) at enrollment in stroke patients, as were Th17 cells and the Th17/Treg cell ratio (all p < 0.050). The 1-, 2-, and 3-year MMSE scores in stroke patients were 25.9 ± 2.0, 25.3 ± 2.3, and 24.9 ± 2.3, respectively. More importantly, serum RBP4 was negatively correlated with 1-, 2-, and 3-year MMSE scores (all p < 0.001) and positively associated with 1-year (p = 0.013), 2-year (p = 0.007), and 3-year (p = 0.001) MMSE score declines in stroke patients. Serum RBP4 is positively associated with a Th17/Treg cell imbalance and, more importantly, it is indicative of cognitive function decline within 3 years in stroke patients. Thus, early and timely interventions and physical rehabilitation are more necessary in stroke patients with high serum RBP4.

Decoupling of Regional Cerebral Blood Flow and Brain Function Along the Alzheimer's Disease Continuum.

Alzheimer's disease (AD) is accompanied with impaired neurovascular coupling. However, its early alteration remains elusive along the AD continuum. This study aimed to investigate the early disruption of neurovascular coupling in cognitively normal (CN) and mild cognitive impairment (MCI) elderly and its association with cognition and AD pathologies. We included 43 amyloid-β-negative CN participants and 38 amyloid-β-positive individuals (18 CN and 20 MCI) from the Alzheimer's Disease Neuroimaging Initiative dataset. Regional homogeneity (ReHo) map was used to represent neuronal activity and cerebral blood flow (CBF) map was used to represent cerebral blood perfusion. Neurovascular coupling was assessed by CBF/ReHo ratio at the voxel level. Analyses of covariance to detect the between-group differences and to further investigate the relations between CBF/ReHo ratio and AD biomarkers or cognition. In addition, the correlation of cerebral small vessel disease (SVD) burden and neurovascular coupling was assessed as well. Related to amyloid-β-negative CN group, amyloid-β-positive groups showed decreased CBF/ReHo ratio mainly in the left medial and inferior temporal gyrus. Furthermore, lower CBF/ReHo ratio was associated with a lower Mini-Mental State Examination score as well as higher AD pathological burden. No association between CBF/ReHo ratio and SVD burden was observed. AD pathology is a major correlate of the disturbed neurovascular coupling along the AD continuum, independent of SVD pathology. The CBF/ReHo ratio may be an index for detecting neurovascular coupling abnormalities, which could be used for early diagnosis in the future.

Malnutrition and Associated Factors in Acute and Subacute Stroke Patients with Dysphagia.

Most patients with stroke suffer from complications and these include dysphagia. Dysphagia can cause malnutrition, and malnutrition affects prognosis and recovery. However, there is a lack of accurate studies on the nutritional status of stroke patients with dysphagia and its associated factors in different phases of stroke. This study retrospectively investigated 620 stroke patients who underwent a videofluoroscopic swallowing study (VFSS) due to dysphagia, from March 2018 to February 2021. The study aimed to evaluate the nutritional state and associated factors of malnutrition in acute and subacute stroke patients with dysphagia. Serum albumin and percentage of current weight to ideal weight were used to determine nutritional status. Malnutrition was observed in 58.9 and 78.9% of acute and subacute stroke patients. Exact logistic regression analysis revealed that old age and high penetration-aspiration scale score were significantly associated factors for malnutrition in patients with acute stroke. Old age, stroke history, bilateral hemiplegia, high modified Rankin score, low Korean Mini-Mental State Examination, pneumonia, and high functional dysphagia score were significantly associated factors for malnutrition in patients with subacute stroke. Patients with these associated factors in each phase of stroke require active nutritional assessment and care to decrease the risk of malnutrition.

Associations between Sedentary Duration and Cognitive Function in Older Adults: A Longitudinal Study with 2-Year Follow-Up.

This study aimed to investigate the association between different forms of sedentary behavior and cognitive function in Chinese community-dwelling older adults. A longitudinal study with a 2-year follow-up. Data from 5356 participants at baseline and 956 participants at the follow-up of the Anhui Healthy Longevity Survey (AHLS) were analysed. Cognitive function was evaluated by the Mini-Mental State Examination (MMSE), and mild cognitive impairment (MCI) was classified according to education-specific criteria. Self-report questionnaires were used to assess the sedentary behavior of the participants. The participants who reported longer screen-watching sedentary duration had higher MMSE scores (1-2 hours: β=0.758, 95% CI: 0.450, 1.066; > 2 hours: β=1.240, 95% CI: 0.917, 1.562) and lower likelihoods of MCI (1-2 hours: OR= 0.787, 95% CI: 0.677, 0.914; >2 hours: OR=0.617, 95% CI: 0.524, 0.726). The participants who had played cards (or mahjong) sedentary had higher MMSE scores (β= 1.132, 95% CI: 0.788, 1.476) and lower likelihoods of MCI (OR=0.572, 95% CI: 0.476, 0.687). However, the participants who reported longer other forms of sedentary duration had lower MMSE scores (1-2 hours: β=-0.409, 95% CI: -0.735, -0.082; > 2 hours: β=-1.391, 95% CI: -1.696, -1.087) and higher likelihoods of MCI (1-2 hours: OR=1.271, 95% CI: 1.081, 1.496; > 2 hours: OR=1.632, 95% CI: 1.409, 1.889). No significant association was detected between sedentary duration and MCI incidence. Variations in the impact of diverse sedentary behaviors on the cognitive function were detected in Chinese older adults. However, such associations were cross-sectional and longitudinal associations were not found in the current study.

Nursing Home Residence, Overweight and Cognitive Status are Related to Falls in Older Adults: A Cross-sectional Study.

Nursing home residents are likely to differ from community older adults when their gait parameters are compared, as nursing home residents present more falls. The study aim was to identify the main fall (occurrence predictors) (anthropometrics, functional and gait-related parameters) between older adults living in community and nursing homes during self-selected (SSWS) and fast walking speeds (FWS). A hundred and sixty-five older adults were selected from the community (n = 92) and nursing home (n = 73) with and without fall history. They were assessed for fall history, functionality, cognitive status, and several gait parameters in SSWS and FWS conditions. Fallers differed from non-fallers in the SSWS, while such differences were not evidenced during the FWS. Cadence and stride width did not differ when living backgrounds were compared. Nursing home residents walked slower than their non-institutionalized peers, regardless of fall history or walking speed. Besides, binary logistic regression analysis showed that living in a nursing home, age, body mass index (BMI), mini-mental state examination (MMSE), and step width were related to falls in the SSWS. On the other hand, living in a nursing home, having a larger BMI and having low MMSE scores were fall predictors in the FWS. Fall occurrence can be identified by factors related to living in nursing homes, cognitive status, BMI, and gait parameters, at the SSWS. Cognitive status and BMI are related to falls in the FWS for those living in nursing homes.

Associations of Leisure Activities and Sleep Duration with Cognitive Function: A Nationwide Prospective Cohort Study of Chinese Old Adults.

Leisure activities and sleep duration are correlated and have been linked to cognitive function, but most studies have examined only one of these factors. To investigate the independent and joint associations of leisure activities and sleep duration with cognitive function among older adults. We included 7,796 participants aged≥65 years from the Chinese Longitudinal Healthy Longevity Survey during 2008-2018 (waves 5-8). Self-reported leisure activities and sleep duration were assessed at baseline, and cognitive function was measured repeatedly using the Chinese version of the Mini-Mental State Examination (MMSE) at baseline and during follow-up. We used linear mixed models to estimate regression coefficients (β) and 95% confidence intervals (CI). The median follow-up duration was 5.77 years. After adjusting for each other and potential confounders, both lower leisure activity score (each 1-point decrease β= -0.33, 95% CI: -0.36 to -0.30) and longer sleep duration (each 1-hour increase β= -0.17, 95% CI: -0.22 to -0.11) were independently associated with lower MMSE score. Furthermore, we observed an additive interaction between leisure activities and sleep duration (pinteraction < 0.001). A combination of low leisure activity score and long sleep duration was strongly associated with decreased MMSE score (β= -2.51, 95% CI: -2.85 to -2.16) compared with the group with combined high leisure activity score and normal sleep duration. Both leisure activities and sleep duration were independently associated with cognitive function. Moreover, the combination of leisure inactivity and prolonged sleep duration predicted worse cognitive function (a preclinical hallmark of Alzheimer's disease) in an additive manner.

Association of Pesticide Exposure with Cognitive Function in Farmers

Introduction: Organophosphate and carbamate are two types of pesticides that can induce cholinesterase suppression in humans. These lead to poisoning symptoms including muscle paralysis and respiratory depression in acute settings. In chronic settings, the mechanism of organophosphate and carbamate poisoning is still openly discussed. Accordingly, this study aimed to identify any correlations between erythrocyte cholinesterase and type of pesticides with cognitive performance of the subjects. Methods: This cross-sectional study was conducted in two sampling periods (July 2017 and October 2018) in Ngablak Districts, Magelang Regency, Central Java, Indonesia. The study subjects were farmers with history of pesticide exposure. Cholinesterase levels (ChE) were analyzed from blood samples. Cognitive performance was assessed using the Mini Mental State Examination (MMSE) and Stroop Test. Results: In total, 151 subjects aged between 23 and 91 years old were included. The long-term organophosphate exposure group had significantly lower MMSE scores compared with other types of pesticides, but not in carbamate (p = 0.017). After comparing “organophosphate only” and “carbamate only” groups, there were significant differences in MMSE scores (p = 0.018) but not in blood ChE levels (p = 0.286). Detailed assessment in MMSE domains showed significantly lower scores for orientation, attention, and registration domains (p < 0.05) in the organophosphate group. There were no significant associations between types of pesticides and blood ChE levels with the Stroop Test results (p > 0.05). Conclusions: Long-term organophosphate exposure could produce lower cognitive function and the insignificant association between blood ChE levels to MMSE could lead to non-cholinergic pathways as its underlying pathology.

The effect of fatigue on the cognitive status and quality of life of patients with Lyme- borreliosis

The relevance of the issue of asthenic disorders is determined by a high prevalence among patients with various chronic pathologies and its impact on the disease course, treatment efficacy, and quality of life. The purpose of the study was to analyze the dependence of cognitive disorders and the quality of life of patients with Lyme borreliosis on the level of fatigue.&#x0D; Materials and Methods. The study involved 48 patients with Lyme borreliosis. The MOS 36-item Short Form Health Survey (SF-36) was used to study the quality of life of patients. Cognitive function was assessed using the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA), and the impact of fatigue was evaluated using the Fatigue Severity Scale (FSS).&#x0D; Results. According to the results of assessing asthenia/fatigue severity (FSS), the prevalence of asthenic disorders in patients with Lyme borreliosis was 45.8%. Cognitive impairment with an MMSE score of &lt;28 was found in 64.6% of patients, and the MoCA score of &lt;26 was revealed in 56.2% of patients. Manifestations of moderate or severe fatigue were more common among women (OR 5.43; 95% CI [1,29-22,94]), patients with neuroborreliosis (OR 13.64; 95% CI [2,62-70,9]), patients with late-stage of disease (OR 9.23; 95% CI [2,46-34,58]), and those with a lower MMSE score (26.14±2.53 vs. 27.54±2.25 scores, р=0.048) and MoCA score (23.59±2.77 vs. 25.46±2.42 scores, р=0.016). Fatigue significantly reduces the quality of life of patients with Lyme-borreliosis, in particular: physical functioning (p=0.002), role physical and role emotional (p&lt;0.001), bodily pain (p=0.037), vitality (p&lt;0.001), social functioning (p=0.048).&#x0D; Conclusions. It was found that the presence of asthenia depends on the gender (female), the presence of clinical manifestations of damage to the nervous system (neuroborreliosis) and cognitive disorders, as well as the late stage of the disease. The presence of fatigue significantly reduces the quality of life of patients with Lyme borreliosis.