Presence Of Mild Cognitive Impairment Research Articles

Association between type of menopause and mild cognitive impairment: The REDLINC XII study

ObjectiveTo evaluate the association between type of menopause (spontaneous or surgical) and mild cognitive impairment (MCI). Study designThis study was a cross-sectional, observational, and sub-analytical investigation conducted within gynecological consultations across nine Latin American countries. MethodWe assessed sociodemographic, clinical, and anthropometric data, family history of dementia, and the presence of MCI using the Montreal Cognitive Assessment (MoCA) tool. ResultsThe study involved 1185 postmenopausal women with a mean age of 55.3 years and a body mass index of 26.4 kg/m2. They had an average of 13.3 years of education, and 37 % were homemakers. Three hundred ninety-nine experienced menopause before 40, including 136 with surgical menopause (bilateral oophorectomy). Out of the 786 women who experienced menopause at 40 or more years, 110 did so due to bilateral oophorectomy. There were no differences in MoCA scores among women who experienced menopause before or after the age of 40. However, lower MoCA scores were observed in women with surgical menopause than in those with spontaneous menopause (23.8 ± 4.9 vs. 25.0 ± 4.3 points, respectively, p < 0.001). Our logistic regression model with clustering of patients within countries found a significant association between MCI and surgical menopause (OR 1.47, 95 % CI: 1.01–2.16), use (ever) of menopausal hormone therapy (OR 0.33, 95 % CI: 0.21–0.50), and having >12 years of education (OR 0.21, 95 % CI: 0.14–0.30). ConclusionWhen comparing women who experience spontaneous menopause over the age of 40 with those who undergo it before this age, there was no observed increased risk of developing MCI, while those with surgical menopause, independent of age, are more prone to cognitive decline. Women who have ever used menopausal hormone therapy have a lower MCI risk. Further research is warranted to delve deeper into this topic.

Quantitative EEG in Parkinson's disease: when REM sleep behavior disorder onset really matters.

Parkinson's Disease (PD) body-first subtype is characterized by prodromal autonomic symptoms and REM sleep behavior disorder (RBD), symmetric dopaminergic degeneration, and increased risk of dementia. On the other hand, the PD brain-first subtype has fewer non-motor symptoms and a milder motor phenotype. The temporal relationship between RBD onset and motor symptoms onset may differentiate these two subtypes. We aimed to investigate electrocortical differences between brain-first and body-first PD patients. PD patients with an available routinely collected EEG were retrospectively selected. RBD was diagnosed using the RBD screening questionnaire (≥ 6). According to the onset of RBD patients were classified into PD-RBDpre (RBD onset before motor symptoms) and PD-RBDpost (RBD onset after motor symptoms). Patients without RBD were classified as PD-RBD-. Presence of Mild Cognitive Impairment (MCI) was diagnosed according to the MDS criteria. EEG Spectral analysis was performed in resting state by computing the Power Spectral Density (PSD) of site-specific signal epochs for the common frequency bands (delta, theta, alpha, beta). Thirty-eight PD-RBD-, 14 PD-RBDpre and 31 PD-RBDpost patients were recruited. Comparing both global and site-specific absolute values, we found a significant trend toward beta band reduction going from PD-RBD-, PD-RBDpost and PD-RBDpre. No significant differences were found between PD-RBDpost and PD-RBD- patients. PD-RBDpre patients may represent a different subset of patients as compared to patients without RBD, while patients with later onset have intermediate EEG spectral features. Quantitative EEG may provide new hints in PD subtyping.

Does periodontitis have any association with mild cognitive impairment?

This study aimed at determining the association between periodontitis and mild cognitive impairment. For this, different electronic databases, including PubMed, Scopus, Embase and Web of Science, were searched for finding the relevant literature. In addition, hand searching of relevant journals was also done to find gray literature. The systematic review included observational studies only. Accordingly, case-control, cohort and cross-sectional studies were searched. The search strategy was based on PECO framework, wherein the studies which included patients with/without periodontitis and patients with/without mild cognitive impairment (MCI)were included. A total of 7 studies were included and the data from these studies and the data including bibliographic details, demographic data, data about periodontitis, presence of MCI etc. was extracted from the included articles. The extracted data, was then assessed for heterogeneity using clinical parameters and I2 statistical test. Owing to low heterogeneity, fixed-effects model was used for meta-analysis. Meta-analysis was done to determine the association between periodontitis and MCI and significantly higher incidence of MCI was found in patients with periodontitis OR = OR, 1.70 (95% CI: 1.24-2.32, p < 0.001). A subgroup analysis was done by including the studies comparing incidence of MCI in patients with severe periodontitis, which resulted in even stronger association with an OR of 2.09 (95% CI: 1.49-2.92, p < 0.001). Lastly, periodontal parameters, including CAL, PPD, and PI were compared amongst patients with/without MCI. Significant differences were observed for both CAL and PI, with worsening of values in patients with MCI. Observed mean difference for CAL and PI were 0.44 (95% CI: 0.12-0.75) and 0.72 (95% CI:0.50-0.93), respectively. NS differences were observed for PPD values with a mean difference of 0.21 and 95% CI as -0.08 to 0.49. Strong association between periodontitis and MCI was observed, indicating periodontitis to be a risk factor for MCI.

Naturalistic assessment of everyday multitasking in Parkinson’s disease with and without mild cognitive impairment

Objective: Multitasking is an essential part of everyday functioning often not formally assessed by traditional neuropsychological tests. Although individuals with Parkinson’s disease (PD) experience both motor and cognitive difficulties, previous research has demonstrated more pronounced functional difficulties with the presence of mild cognitive impairment (PD-MCI). The current study compared individuals with PD-MCI, PD with normal cognition (PD-NC), and healthy controls on a naturalistic task of multitasking, the Day Out Task (DOT). Method: Participants were 38 healthy older adults (HOA), 23 individuals with PD-NC, and 15 individuals with PD-MCI. Participants completed a battery of neuropsychological tasks and the DOT. Informants also completed a self-reported questionnaire of participants’ everyday executive functioning. Results: Compared to PD-NC and HOA, participants with PD-MCI were less accurate and efficient and took longer to complete the DOT. After controlling for motor performance, only DOT accuracy remained worse, with poorer accuracy resulted from more subtasks being left incomplete or being completed inaccurately by the PD-MCI group. DOT sequencing was a significant predictor of informant reported everyday dysexecutive symptoms. Conclusions: The findings highlight that individuals with PD-MCI are likely to experience difficulties completing complex everyday tasks due to both motor and cognitive impairments. Clinicians may therefore recommend strategies to support efficiency and accuracy in complex tasks of everyday functioning in treatment considerations.

Analysis of the correlations between the extracranial internal carotid artery and extracranial vertebral artery and mild cognitive impairment.

Vascular tortuosity is a prevalent morphological change that frequently occurs in arteries across different parts of the body. To analyze the relationship between the tortuosities of the extracranial internal carotid artery (EICA) and extracranial vertebral artery (EVA) with mild cognitive impairment. The tortuosity index (TI), vascular deviation degree, tortuosity degree, and angle number of the EICA and EVA were retrospectively analyzed and calculated in 160 patients who underwent computed tomography angiography (CTA) in this study's department, and the Montreal cognitive assessment was adopted to evaluate the cognitive function of the patients. The differences in age, gender, arterial hypertension (AH), and diabetes mellitus (DM) between the normal group and the mild cognitive impairment group were statistically significant (p< 0.01). The TI was negatively correlated with the score of cognitive function. The tortuosities of the EICA and EVA were correlated with mild cognitive impairment (p< 0.05). The reduction in visual-spatial ability was correlated with the right EICA tortuosity, and the reduction in memory was correlated with the EVA tortuosity. Age, gender, HP, DM, and coronary heart disease (CHD) were potential risk factors for carotid tortuosity (p< 0.05). There was a significant correlation observed between the TIs of both the EICA and EVA and the presence of mild cognitive impairment. Advanced age, female, HP, DM, and CHD were independent risk factors for EICA and EVA tortuosities.

Kinematic and Kinetic Gait Features Associated with Mild Cognitive Impairment in Parkinson's Disease.

Mild cognitive impairment (MCI) and gait deficits are commonly associated with Parkinson's disease (PD). Early detection of MCI associated with Parkinson's disease (PD-MCI) and its biomarkers is critical to managing disability in PD patients, reducing caregiver burden and healthcare costs. Gait is considered a surrogate marker for cognitive decline in PD. However, gait kinematic and kinetic features in PD-MCI patients remain unknown. This study was designed to explore the difference in gait kinematics and kinetics during single-task and dual-task walking between PD patients with and without MCI. Kinematic and kinetic data of 90 PD patients were collected using 3D motion capture system. Differences in gait kinematic and kinetic gait features between groups were identified by using: first, univariate statistical analysis and then a supervised machine learning analysis. The findings of this study showed that the presence of MCI in PD patients is coupled with kinematic and kinetic deviations of gait cycle which may eventually identify two different phenotypes of the disease. Indeed, as shown by the demographical and clinical comparison between the two groups, PD-MCI patients were older and more impaired. Moreover, PD-MCI kinematic results showed that cognitive dysfunction coexists with more severe axial symptoms and an increase postural flexion. A lack of physiological distal-to-proximal shift in joint kinetics was evidenced in the PD phenotype associated with cognitive impairments.

The association between oral health and mild cognitive impairment in community-dwelling older adults.

Older adults with cognitive impairment can experience poor oral health due to reduced self-care ability, yet the impact of various oral health indicators on the cognitive ability remains unclear. We investigated the relationship between oral health indicators and mild cognitive impairment (MCI) in older adults. A cross-sectional study of 234 older adults aged 65 years or over was performed form January to March 2023 at health screening departments of hospitals. This study used the Mini-mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Activities of Daily Living (ADL), Clinical Dementia Rating (CDR), and Hachinski Ischemic Score (HIS) to measure MCI. Two qualified dentists performed clinical oral examinations (number of teeth lost, dental caries, removable dentures, periodontitis). The other oral health status was measured by subjective assessment questionnaires, and the oral health-related quality of life (OHRQoL) was assessed by Geriatric Oral Health Assessment Index (GOHAI). Of the 234 older adults, 166 had MCI and 68 had normal cognitive ability. The univariate analyses revealed that older adults with poor oral health indicators of dental caries, mastication ability, oral and maxillofacial pain, self-perceived oral health status and OHRQoL had lower cognitive levels. The stepwise logistic regression analysis observed that higher education level (OR = 0.06, 95%CI = 0.007, 0.567) and OHRQoL score (OR = 0.92, 95%CI = 0.878, 0.963) were negatively associated with the presence of MCI. The area under the ROC curve (AUC) of MCI was 0.675 (95% CI: 0.600, 0.749) with a low sensitivity of 41.6% and a moderate specificity of 86.8%. OHRQoL was found to be associated with MCI, implying that OHRQoL may be important in cognitive decline. The GOHAI scale can be used to more easily assess the oral health of older adults, which is important for the timely detection of poor oral status to delay cognitive decline.

Enhanced memory for negative words is associated with amnestic mild cognitive impairment and in vivo cerebral amyloid‐β burden independently of depression

AbstractBackgroundEmotion dysregulation was studied as a potential risk marker for Alzheimer’s disease (AD) by assessing emotional memory in high AD‐risk groups characterized by the presence of mild cognitive impairment (MCI) or remitted major depressive disorder (rMDD) and by evaluating the relationship between emotional memory and in vivo cerebral amyloid‐β deposition.Method435 participants enrolled in the PACt‐MD clinical trial of cognitive remediation plus transcranial direct current stimulation were evaluated at baseline. The sample included 127 older adults with amnestic mild cognitive impairment (aMCI), 51 non‐amnestic MCI (naMCI), 60 rMDD without MCI, 81 rMDD+aMCI, 42 rMDD+naMCI, and 74 cognitively unimpaired older adults (CU). Diagnoses were established during a consensus conference based on psychiatric, medical, and neuropsychological assessment. Emotional memory was assessed by evaluating immediate and short‐term delayed recall of 15 personality adjectives (5 each of positive, negative and neutral words) from the Emotional Verbal Learning Test (Mah et al., 2017, American Journal of Geriatric Psychiatry, 25:1160). A subset (N = 167) completed a Positron Emission Tomography (PET) scan with carbon‐11 Pittsburgh Compound B ([11C] PIB). Valence and diagnostic group effects on recall were assessed using mixed ANOVA. Regression modelling assessed the association between emotional memory bias and amyloid‐β burden.ResultRelative to CU, both aMCI and rMDD+aMCI groups showed enhanced memory for negative words at immediate recall, which persisted after short delay in the aMCI group only (F(1, 339) = 2.66, p = .048; Figure 1). Enhanced memory for negative words at short delay was predictive of in vivo cerebral amyloid‐β deposition (standardized beta = .117, t = 1.84, p = .067), over and above the contributions of age, sex, Apolipoprotein E genotype, depression diagnosis and symptoms, and long delayed verbal recall (F(4,154) = 25.8, p&lt;.001, R2 = .41; Figure 2).ConclusionThe association between enhanced memory for negative personality adjectives and aMCI replicates earlier work in single‐domain aMCI (Mah et al., 2017) and suggests that aMCI is characterized by a negativity bias in memory. These findings, taken together with the relationship between a negativity bias in memory and amyloid‐β burden, suggest that emotion dysregulation, in the form of enhanced memory for negative information, is a potential marker of AD risk.

Prevalence of Mild cognitive impairment (MCI) in a rural Indian population and its association with hypertension, diabetes and depression

AbstractBackgroundMild cognitive impairment (MCI) is a transitional phase between normal cognitive ageing and dementia. The prevalence of MCI in rural populations is an understudied area. Risk factors such as hypertension, diabetes, and depression are more prevalent in rural areas, which can contribute to the development of MCI (Longfei et al, 2020). The purpose of this study is to find out the prevalence of MCI amongst a rural cohort and to study the relationship between MCI and hypertension, diabetes and depression.MethodCross sectional analysis on the subset of data taken from ongoing longitudinal study on dementia named Srinivaspura Aging, Neuro Senescence and COGnition (SANSCOG) (Sundarakumar et al, 2020), which has a target of 10000 participants. MCI was diagnosed in the subject whose Clinical Dementia Rating (CDR) score was 0.5, as per the NIA‐AA (National Institute on Aging‐Alzheimer’s Association) criteria, 2011. Presence of hypertension and diabetes were collected through a structured clinical questionnaire. Depression was assessed using the Geriatric Depression Scale 30 (GDS‐30) and a score above 9 was considered as depression. Chi‐square analysis(χ2) was used to study the association between MCI and hypertension, diabetes and depression.ResultA total of 3789 participants were examined amongst which 293 had a CDR score of 0.5, indicating presence of MCI in 7.7% of the study group. Prevalence of depression in non‐MCI and MCI subjects was 14.91% and 30.73% respectively and depression was found to be significantly associated with MCI(χ2 =24.522, p&lt; 0.001). Hypertension was seen in 13.83% of non‐MCI subjects and in 17.76% of subjects with MCI. Diabetes was seen in 16.93% of non‐MCI subjects and in 18.25% of subjects with MCI. Both hypertension (χ2 =2.086, p = 0.149) and diabetes (χ2=0.195, p = 0.659) were not significantly associated with MCI.ConclusionDepression was significantly associated with MCI. It is known that late onset depression, which is diagnosed above the age of 50, may be a predisposing factor for dementia in later life. Our results may indicate this relationship between depression and cognitive impairment. However, further longitudinal studies are necessary to evaluate causal relationship.

P174: Project Connect 80+

Introduction:-Patients with a memory deficit, as well as patients with small deficits in various cognitive areas, with the requirement that there is no functional impairment in their domestic or work life, do not meet the criteria to be diagnosed with dementia, but they do meet the criteria for a diagnosis of mild cognitive impairment (MCI), which constitutes a transitional state between normal aging and mild dementia.-Every year, 15% of patients with MCI with involvement only in the memory section, go on to be diagnosed with dementia.In recent years, the use of a food for special medical purposes (FSMP), Souvenaid®, has been introduced into clinical practice, which, due to the composition of its active ingredient, Fortasyn connect (omega-3 fatty acids, uridine, choline, vitamins C, E, B6 and B12, selenium and folic acid) helps to: •Promote the development of neuronal synapses, demonstrating that it maintains the integrity of white and gray matter.•Reduce loss of functional connectivity.•Increase hippocampal cholinergic synapses and cholinergic neurotransmission.•Improve cognitive performance dependent on the hippocampusObjective:A survey has been developed to explore the impact of a nutritional intervention, through the use of an FSMP in the areas related to cognition, functionality, and behavior, in a geriatric cohort with MCI older than 80 years. (Connect - Survey in the environment of mild cognitive impairment).Survey: Each Geriatrics and Neurology professional had to select 5 cases that met the following characteristics: Presence of MCI, Age ≥ 80 years, and Receiving Souvenaid.The professional sent CRO Alpha Bioresearch the list of caregivers with their contact details. The CRO contacted the subjects by telephone 3, 6, and 12 months after starting Souvenaid to carry out the survey.Methodology:The survey collects the perception of the patient and caregiver's cognition, functionality, and behavior, through a Likert scale with 5 possible response alternatives. The questionnaire is divided into two different parts: –Data about the treatment (questions 1 to 5)–Questions about the patient's health (questions 1 to 12);The last one is divided into three parts: data on cognition 3 questions (questions 1 to 3), data on functional abilities with 5 questions (questions 4 to 8), and data on behavior 4 questions (questions 9 to 12).Results:Regarding the treatment at 12 months, there is a tolerance that reaches 76%, and 88% do not present problems with the administration of what is prescribed. The most common time of day for administration is breakfast and snacks. The most used flavor was vanilla and cappuccino. The most common way to acquire it was the direct route.Regarding cognitive functions, the ability to remember is improved by 20%, orientation by 12%, and recognition by 8%, maintaining stability without changes by around 60-70%. Functional capacities improved between 8 and 16%, presenting no changes between 68-80%. Regarding the behavior, the improvement is between 12 to 28% in the evaluated items, presenting no changes between 60-84%.Conclusions:There is stabilization at 3, 6, and 12 months both in cognition, functionality, and behavior. The positive impression of the perceived improvement in memory (around 20%) and apathy (exceeding 20% and reaching 28% per year) are striking.

7 The MOCA Versus Neuropsychological Testing in Assessing Presence of Memory Impairment and MCI

Objective:The Montreal Cognitive Assessment (MOCA) is a brief cognitive screener, widely used by providers to detect mild cognitive impairment (MCI). It encompasses 30 questions, assessing executive functioning, visuospatial skills, language, memory, attention, and orientation. Although the MOCA has been shown to have high sensitivity (90%) and specificity (87%) for detecting MCI, existing studies have primarily included participants who were already diagnosed with amnestic MCI via neuropsychological testing. Since several factors beyond the presence of MCI can contribute to low performance on the MOCA (e.g., premorbid IQ, fatigue, mood symptoms), over-reliance on the MOCA runs the risk of falsely identifying individuals as having cognitive impairment. The MOCA’s memory subtest raises particular concern as there are several language-based tasks between the learning and delay trials, introducing the potential for interference effects. Thus, the MOCA’s ability to accurately identify those at risk for MCI in the community remains unclear. The objective of the present study was to evaluate: (1) the MOCA’s association with neuropsychological memory measures; and (2) its ability to distinguish between neurocognitive groups (intact vs. MCI vs. dementia).Participants and Methods:This study involved a retrospective analysis of fifty-one patients (M age=72.58 [7.90]; M education= 16.37 [16.37]) who underwent neuropsychological evaluation. Standardized scores for total list-learning (HVLT; CVLT-bf) were used to capture memory encoding; retention % scores were used to capture memory storage. MOCA scores included Total MOCA, MOCA-Orientation, and the MOCA Memory Index (MOCA-MEM). MOCA-MEM was calculated based on Julayanont et al., 2014— (Free-Delayed Recall*3) + (Category-Cued Recall*2) + Multiple Choice-Cued Recall. Bivariate correlations were conducted for the MOCA and neuropsychological test scores. Participants were divided into three diagnostic groups, classified by the neuropsychologist: (1) Cognitive Intact (CI; n=13); (2) MCI (n=26); and (3) Major Neurocognitive Disorder/Dementia (MNCD; n=11). Analysis of covariance was used to analyze differences between the cognitive groups on Total MOCA, MOCA-Orientation, and MOCA-MEM.Results:Total MOCA correlated with word-list learning (r=.434, p=.004) and retention% (r=.306, p=.049). MOCA-MEM was correlated with word-list learning (r=.367, p=.042); it did not significantly correlate with retention%. MOCA-Orientation had the strongest correlation with retention0/) (r=.406, p=.009). Means of Total MOCA significantly differed between CI (25.31[2.56]), MCI (22.04[4.14]), and MNCD (15.44[4.13]). MOCA-MEM only differentiated CI (10[3.66]) and MNCD (5.71[2.14]); it did not differentiate MCI (6.94[3.13]) from either CI or MNCD.Conclusions:Our findings suggest that the MOCA has limitations in accurately classifying memory deficits in older adults. First, our study suggests that the MOCA-MEM reflects encoding rather than memory storage. Given that deficiency in encoding may be secondary to other cognitive deficits, such as attention and executive dysfunction, performance on MOCA-MEM cannot readily delineate the presence of an amnestic process. Second, the findings show that MOCA-MEM does not differentiate between patient groups with intact cognition versus MCI, nor those with MCI versus MNCD. These findings argue the importance of neuropsychological evaluation in deciphering patterns of memory performance and the presence of an amnestic process.

P01.09.A THE NEUROCOGNITIVE FUNCTIONING OF LOWER GRADE GLIOMA PATIENTS BEFORE START OF RADIOTHERAPY IS ASSOCIATED WITH THE RADIOLOGICAL APPEARANCE OF THE BRAIN

Abstract BACKGROUND The cause for neurocognitive function (NCF) impairments in patients with lower grade glioma (LGG) is typically multifactorial. The aim of this study was to explore the relationship between NCF and the radiological appearance of the brain before start of radiotherapy (RT) in LGG patients. MATERIAL AND METHODS Around start of RT we evaluated NCF of LGG patients treated with proton therapy. The assessment included 10 neuropsychological tests with 20 measures that could be categorized over 6 cognitive domains. Raw test scores were converted to Z scores based on normative data. Mild cognitive impairment (MCI) was defined as a Z score of less than -2 on a single measure, or Z score of less than -1.5 on multiple measures. An impaired cognitive domain was defined as a mean composite Z score of less than -1.5. The radiological appearance of the brain outside the tumor region was assessed on a pre-RT planning MRI using the Fazekas score and Global Cortical Atrophy (GCA) score. For statistical analysis we used Chi Square tests and Mann-Whitney U tests. RESULTS Between 2018 and March 2022, 126 LGG patients started RT treatment, 119 patients (94%) had NCF assessment pre-RT and were available for analysis. Median age was 41 years, 51% of patients was male, reported comorbidities included hypertension in 7%, diabetes mellitus in 3% and cardiovascular 13% of patients. The World Health Organization (WHO) performance scores and the Neurologic Assessment in Neuro-Oncology (NANO) scores were 0 - 1, in 98%, and 92% of patients. The Fazekas score was 0 in 75%, 1 in 18% and 2 in 6% and 3 in 2% of patients. The GCA score was 0 in 59%, 1 in 38%, 2 in 3% of patients. In 77 (65%) patients the performance on the NCF assessment indicated the presence of MCI. Patients with MCI had a significant radiologically worse appearance of the brain (Fazekas score 1 or higher 31.2% versus 14.3%, p = 0.043; and GCA score 1 or higher 49.4% versus 26.2%, p = 0.014). Domain impairments were present in executive functions and attention (26%); verbal memory (23%); verbal functions (20%); non-verbal memory (20%); processing speed (18%); and working memory (14%). Fazekas score 1 or higher was significantly associated with lower composite Z scores of verbal functions (median (IQR) -0.84 (1.12) versus -0.40 (0.94), p=0.014); verbal memory (median (IQR) -0.66 (1.26) versus -0.20 (1.35), p=0.045) and non-verbal memory (median (IQR) -0.45 (2.10) versus -0.20 (1.36), p=0.037). There were no significant associations found between the GCA score and domain composite scores. CONCLUSION This cohort of LGG patients had a good clinical and neurological baseline function pre-RT. We found significant relationships between NCF and both white matter damage and atrophy of the brain. The Fazekas and GCA score are objective and easily obtained radiological measures, that could be a relevant parameter to record in LGG patients.

Serum microRNA-501-3p is a potential diagnostic tool for detecting mild cognitive impairment: Ehime genome study.

Tight junction disruption and dysfunction are involved in the progression of blood-brain barrier (BBB) breakdown. Recent investigations have revealed BBB disruption in patients with vascular cognitive decline. Our previous studies showed that miR-501-3p negatively regulates cerebral endothelial tight junction protein-1, resulting in the disruption of the BBB, and playing an important role in the development of vascular cognitive impairment. BBB breakdown in white matter lesions is often seen in the patients with vascular mild cognitive impairment (MCI). We therefore hypothesize that most early-phase MCI patients may demonstrate elevated expression of miR-501-3p and sought to investigate whether serum exosome miR-501-3p levels could be a clinical indicator for detecting mild cognitive impairment. One hundred and seventy-eight subjects (aged 73 [68-75] years, 53% male) were recruited for this study. The Japanese version of the Montreal Cognitive Assessment (MoCA-J) was used for detecting MCI. Serum exosome miR-501-3p expression levels were measured by qPCR methods. Patients were divided into two groups depending on whether their miR-501-3p ∆Ct values were above ("High"; n = 74) or below ("Low"; n = 104) cutoff levels determined by ROC curve. MCI was detected significantly more often in the miR-501-3p-High group (vs. -Low group, 63.5% vs. 47.1%, respectively; p < 0.05). Multivariate logistic regression analysis showed a significant association between MCI status and High miR-501-3p (odds ratio 2.662; p < 0.01), improved vs. known risk factors. In non-diabetic patients, High miR-501-3p was positively associated with MCI status (odds ratio 3.633; p < 0.01) and also positively associated with MCI status in those with atherosclerosis (odds ratio 3.219; p < 0.01). The present study demonstrates that elevated expression of blood exosomal miR-501-3p can indicate the presence of MCI in human patients. Early detection of vascular injuries may allow a reduction in progressive dementia through the management of vascular risk factors.

Functionality according to frailty and cognitive status: Differences between scoring procedures for the Lawton‐Brody IADL scale

AbstractBackgroundFrailty is the state of physiological vulnerability that hindered age‐related decline that precedes disability. However, some functional decline in IADLs is expected, particularly when co‐occurring with Mild Cognitive Impairment (MCI). Our aim was to analyze differences in IADLs between prefrailty and frailty participants with or without MCI. Three scoring procedures for the Lawton &amp; Brody Scale administered to informants were used to analyze IADL differences: 1) Raw scoring: percentage calculation of the raw scores considering all the items; 2) Gender‐corrected scoring: percentage calculation of the IADLs that continue to be carried out but excluding in men the 3 elements traditionally associated with the female gender role (i.e., housekeeping, food preparation, and laundry); 3) Past‐performance corrected scoring: percentage calculation of the IADL activities that the person could perform in the past but now performs with greater difficulty or no longer performs.MethodThe sample comprised 285 Spanish community‐dwelling older adults, without diagnosis of dementia nor disability. MoCA test was used to objectively measure cognitive functioning. Participants were classified using the frailty phenotype: No‐frailty (i.e., met no criteria), pre‐frailty (i.e., met one‐two criteria), and frailty (i.e., met three or more criteria). Presence of MCI were considered to further classify the participants considering cognitive status.ResultsDifferences between No‐frailty (N = 80), (Pre)frailty without MCI (N = 123), and (Pre)frailty with MCI (N = 62) groups were tested using non‐parametric tests (see Figure 1). Group differences (Kruskal‐Wallis tests) were found using Raw (H = 11.30, p&lt;0.01) and Past‐performance corrected scores (H = 10.57, p&lt;0.01). For both, lower IADL scores were found in the (Pre)frailty with MCI compared with the No‐frailty group (Raw scoring: Z = ‐3,37, p&lt;0.01; Past‐performance corrected scoring: Z = ‐1,97, p&lt;0.05) and compared with (Pre)frailty without MCI group (Raw scoring: Z = ‐2,86, p&lt;0.01; Past‐performance corrected scoring: Z = ‐2,65, p&lt;0.01).ConclusionDifferences in IADLs were found between groups with and without MCI using raw and proportional scores considering past performance skills. Between‐group differences in participants without cognitive impairment did not reach significance regardless of their frailty status. Results using the gender‐corrected score suggest a lower sensitivity for detecting functional impairment in men when this procedure is used.

Neuropsychological evaluation of phenoconversion risk in REM sleep behaviour disorder: A scoping review.

The objective of this study was to assess the role of cognitive evaluation in the prediction of phenoconversion in polysomnography-confirmed idiopathic or isolated rapid eye movement sleep behaviour disorder, through a scoping review focussing on a longitudinal comprehensive neuropsychological assessment of patients with idiopathic REM sleep behaviour disorder. A literature search (2006-2022) yielded 1034 records, and 20 were selected for analysis. The sample included 899 patients from eight different cohorts and five countries. We extracted data on clinical evolution, mild cognitive impairment diagnosis, neuropsychological tests used, and classification of cognitive domains. Tests, cognitive domains, and mild cognitive impairment definitions were heterogeneous across the studies, precluding a meta-analysis. Ten studies (50%) evaluated the presence of mild cognitive impairment; 14 studies (70%) grouped neuropsychological tests into between three (6 studies, 21.4%) and seven (1 study, 7.1%) cognitive domains. The most frequently used tests were semantic fluency, Stroop colour word test, trail making test A and B, digit span, Rey auditory verbal learning test, and Rey-Osterrieth figure. All except digit span showed a role in predicting phenoconversion. The authors did not consistently assign tests to specific cognitive domains. In conclusion, we discuss methodological differences between the studies and highlight the need for a standardised framework for neuropsychological data acquisition and presentation, based on a multilevel approach covering test selection, domain assignment, and mild cognitive impairment diagnostic criteria.

Influence of RBD onset on the clinical characteristics of Parkinson's disease patients: a retrospective study.

In Parkinson's disease (PD), rapid eye movement (REM) sleep behavior disorder (RBD) might either precede the appearance of motor symptoms, or develop during the disease course. PD patients with RBD are characterized by a higher burden of cognitive impairment and hallucinations. However, few studies have analyzed the clinical characteristics of PD patients according to the timeline of RBD onset. PD patients have been retrospectively enrolled. Presence and onset of probable RBD (pRBD) has been evaluated using RBD Screening Questionnaire (score ≥ 6). Presence of Mild Cognitive Impairment (MCI) at baseline has been evaluated using the MDS criteria level II. Presence of motor complications and hallucinations has been evaluated at a 5-year follow-up. A total of 115 PD patients (65 men, 56.5%; mean age 62.5 ± 9.7years; mean disease duration 3.7 ± 3.9years) have been enrolled. Out of these, 63 fulfilled the diagnosis of pRBD (54.8%) with 21 (33.3%) reporting the RBD onset before the onset of the motor symptoms (PD-RBDpre), and 42 (66.7%) after the motor symptoms (PD-RBDpost). At enrolment presence of MCI was associated with PD-RBDpre patients (OR 5.04; 95% CI 1.33-19.05; p value 0.02). At follow-up, a higher risk of developing hallucinations was also associated with PD-RBDpre (OR 4.68; 95% CI 1.24-17.63; p = 0.022). PD patients with RBD occurring before the onset of motor symptoms represent a subgroup of patients with a more severe cognitive phenotype and with a higher risk of developing hallucinations along the disease course, with significant implications in terms of prognostic stratification and therapeutic approach.

New possibilities for the treatment of mild cognitive impairment and prevention of dementia in patients with cerebrovascular disease. Results of the PRIORITET Observation Program

A common tool for detecting mild cognitive impairment (MCI) is the Montreal Cognitive Assessment (MoCA). An extension of the standard MoCA testing – MoCA-Memory Index Score (MoCA-MIS; Memory Index, MI) – allows a deeper study of the mechanisms of MCI formation. We consider the drug Prospecta as an effective measure to prevent the progression of MCI. Objective : to study the efficacy and safety of Prospecta in the treatment of MCI in patients with cerebrovascular disease (CVD) in real clinical practice. Material and methods . The observational program PRIORITET included 192 patients of both sexes aged 40 to 74 years inclusive (mean age 63.6±8.8 years) with MCI and CVD, they were prescribed Prospecta, two tablets twice a day during 24 weeks. The presence of MCI was confirmed by testing on the MoCA scale; MI was assessed additionally`. At the end of treatment, the condition of patients was assessed using the Overall Clinical Impression Scale and the safety of the therapy. Results . The change in the mean score on the MoCA scale after 24 weeks of therapy with Prospecta was 5.3 (p&lt;0.0001). The proportion of patients who responded positively to treatment with Prospecta and after 24 weeks of treatment restored their cognitive functions to normal (MoCA &gt;26 points), reached 48.9%. Additionally, patients were divided into groups depending on the results of testing on the MoCA scale and MI. During therapy with Prospecta, the number of patients in the MIS &lt;7 and MoCA &lt;20 group decreased by 19 times, in the MIS &lt;7 or MoCA &lt;20 group – by 4.8 times. There were 16 adverse events, 75% of which were mild. In 62.5% of adverse events, there was no connection with taking Prospecta. Conclusion . Prospecta is an effective and safe treatment for patients with MCI and CVD.

Frequency and Correlates of Mild Cognitive Impairment in Myasthenia Gravis

Antibodies against acetylcholine receptors (AChRs) can also target nicotinic AChRs that are present throughout the central nervous system, thus leading to cognitive dysfunctions in patients with myasthenia gravis (MG). However, the presence of cognitive impairment in MG is controversial, and the factors that may influence this risk are almost completely unknown. In this study, the frequency of mild cognitive impairment (MCI) in MG, as well as the clinical, immunological, and behavioral correlates of MCI in MG were evaluated. A total of 52 patients with MG underwent a comprehensive assessment including motor and functional scales, serological testing, and neuropsychological and behavioral evaluation. The frequency of MCI was 53.8%, and the most impaired cognitive domains were, in order, visuoconstructive/visuospatial skills, memory, and attention. After multivariate analysis, only pyridostigmine use was inversely associated with the presence of MCI, while a trend toward a positive association between MCI and disease severity and arms/legs hyposthenia was found. Correlation analyses showed that daily doses of prednisone and azathioprine significantly correlated with depressive symptomatology, while disease severity significantly correlated with depressive symptomatology and sleep disturbance. The presence of MCI is rather frequent in MG and is characterized by multidomain amnestic impairment. Such preliminary data need further confirmation on larger case series.

Neuropsychological Changes in Isolated REM Sleep Behavior Disorder: A Systematic Review and Meta-analysis of Cross-sectional and Longitudinal Studies.

The aim of this meta-analysis is twofold: (a) to assess cognitive impairments in isolated rapid eye movement (REM) sleep behavior disorder (iRBD) patients compared to healthy controls (HC); (b) to quantitatively estimate the risk of developing a neurodegenerative disease in iRBD patients according to baseline cognitive assessment. To address the first aim, cross-sectional studies including polysomnography-confirmed iRBD patients, HC, and reporting neuropsychological testing were included. To address the second aim, longitudinal studies including polysomnography-confirmed iRBD patients, reporting baseline neuropsychological testing for converted and still isolated patients separately were included. The literature search was conducted based on PRISMA guidelines and the protocol was registered at PROSPERO (CRD42021253427). Cross-sectional and longitudinal studies were searched from PubMed, Web of Science, Scopus, and Embase databases. Publication bias and statistical heterogeneity were assessed respectively by funnel plot asymmetry and using I2. Finally, a random-effect model was performed to pool the included studies. 75 cross-sectional (2,398 HC and 2,460 iRBD patients) and 11 longitudinal (495 iRBD patients) studies were selected. Cross-sectional studies showed that iRBD patients performed significantly worse in cognitive screening scores (random-effects (RE) model = -0.69), memory (RE model = -0.64), and executive function (RE model = -0.50) domains compared to HC. The survival analyses conducted for longitudinal studies revealed that lower executive function and language performance, as well as the presence of mild cognitive impairment (MCI), at baseline were associated with an increased risk of conversion at follow-up. Our study underlines the importance of a comprehensive neuropsychological assessment in the context of iRBD.

Frequency and Underlying Pathology of Pure Vascular Cognitive Impairment

It is not clear how common pure vascular cognitive impairment (VCI) is in the absence of Alzheimer disease (AD) and/or other neurodegenerative pathologies. To identify participants without AD and other neurodegenerative pathologies and determine the extent to which cerebrovascular disease pathologies were associated with cognitive impairment. This clinical pathological study included participants from 2 ongoing community-based cohorts that began enrollment in 1994 and 1997. Prior to death, participants were observed for a mean (SD) of 8.4 (5.3) years with annual assessments. From 2096 participants who died, 1799 (85.8%) underwent autopsy and 1767 had complete postmortem pathological examination data at the time of data analyses. To identify participants without neurodegenerative pathologies, we categorized them in 3 subgroups. A vascular subgroup was composed of participants without significant levels of neurodegenerative brain pathologies. A neurodegenerative subgroup was composed of participants without significant levels of cerebrovascular disease pathologies. A mixed subgroup was composed of the rest of the participants. Data were analyzed from May 2021 to July 2022. Brain pathology indices obtained by postmortem pathological assessments. The primary outcome was cognitive impairment defined by presence of mild cognitive impairment or dementia. The secondary outcome was cognition assessed by 19 neuropsychological tests. Of 1767 included participants, 1189 (67.3%) were women, and the mean (SD) age at death was 89.4 (6.6) years. In the vascular subgroup (n = 369), cognitive impairment was present in 156 participants (42.3%) and was associated with cerebrovascular disease pathologies (macroinfarcts: odds ratio [OR], 2.05; 95% CI, 1.49-2.82; P < .001; arteriolosclerosis in basal ganglia: OR, 1.35; 95% CI, 1.04-1.76; P = .03) but not AD or other neurodegenerative pathologies, an indication of pure VCI. In mixed-effects models including all the pathologies, only macroinfarcts were associated with a faster cognitive decline rate (estimate, -0.019; SE, 0.005; P < .001) in the vascular subgroup. Further analyses identified macroinfarcts in the frontal white matter to be associated with faster cognitive decline rate when macroinfarcts of cortical and subcortical brain regions were examined in a single model. In this study, pure VCI was not rare. Macroinfarcts, specifically in frontal white matter, were the main cerebrovascular disease pathologies associated with cognitive decline in pure VCI.