Mild Cognitive Impairment Syndrome Research Articles

Distinct Patterns of Brain Atrophy in Amnestic Mild Cognitive Impairment and Motoric Cognitive Risk Syndromes.

Motoric cognitive risk (MCR) and amnestic mild cognitive impairment (aMCI) syndromes are each reliable predictors of incident Alzheimer's disease (AD), but MCR may be a stronger predictor of vascular dementia than AD. This study contrasted cortical and hippocampal atrophy patterns in MCR and aMCI. Cross-sectional data from 733 older adults without dementia or disability (M age = 73.6; 45% women) in the multicountry MCR consortium were examined. MCR was defined as presence of slow gait and cognitive concerns. Amnestic MCI was defined as poor episodic memory performance and cognitive concerns. Cortical thickness and hippocampal volumes were quantified from structural MRIs. Multivariate and univariate general linear models were used to examine associations between cortical thickness and hippocampal volume in MCR and aMCI, adjusting for age, sex, education, total intracranial volume, white matter lesions, and study site. The prevalence of MCR and aMCI was 7.64% and 12.96%, respectively. MCR was associated with widespread cortical atrophy, including prefrontal, insular, cingulate, motor, parietal, and temporal atrophy. aMCI was associated with hippocampal atrophy. Distinct patterns of atrophy were associated with MCR and aMCI. A distributed pattern of cortical atrophy - that is more consistent with VaD or mixed dementia- was observed in MCR. A more restricted pattern of atrophy - that is more consistent with AD - was observed in aMCI. The biological underpinnings of MCR and aMCI likely differ and may require tailored interventions.

Non-literacy biased, culturally fair cognitive detection tool in primary care patients with cognitive concerns: a randomized controlled trial.

Dementia is often undiagnosed in primary care, and even when diagnosed, untreated. The 5-Cog paradigm, a brief, culturally adept, cognitive detection tool paired with a clinical decision support may reduce barriers to improving dementia diagnosis and care. We performed a randomized controlled trial in primary care patients experiencing health disparities (racial/ethnic minorities and socioeconomically disadvantaged). Older adults with cognitive concerns were assigned in a 1:1 ratio to the 5-Cog paradigm or control. Primary outcome was improved dementia care actions defined as any of the following endpoints within 90 days: new mild cognitive impairment syndrome or dementia diagnoses as well as investigations, medications or specialist referrals ordered for cognitive indications. Groups were compared using intention-to-treat principles with multivariable logistic regression. Overall, 1,201 patients (mean age 72.8 years, 72% women and 94% Black, Hispanic or Latino) were enrolled and 599 were assigned to 5-Cog and 602 to the control. The 5-Cog paradigm demonstrated threefold odds of improvement in dementia care actions over control (odds ratio 3.43, 95% confidence interval 2.32-5.07). No serious intervention-related adverse events were reported. The 5-Cog paradigm improved diagnosis and management in patients with cognitive concerns and provides evidence to promote practice change to improve dementia care actions in primary care.ClinicalTrials.gov: NCT03816644 .

Bodily and Visual-Cognitive Navigation Aids to Enhance Spatial Recall in Mild Cognitive Impairment.

Individuals with mild cognitive impairment (MCI) syndrome often report navigation difficulties, accompanied by impairments in egocentric and allocentric spatial memory. However, studies have shown that both bodily (e.g., motor commands, proprioception, vestibular information) and visual-cognitive (e.g., maps, directional arrows, attentional markers) cues can support spatial memory in MCI. We aimed to assess navigation cues for innovative spatial training in aging. Fifteen MCI patients were recruited for this study. Their egocentric and allocentric memory recall performances were tested through a navigation task with five different virtual reality (VR) assistive encoding navigation procedures (bodily, vision only, interactive allocentric map, reduced executive load, free navigation without cues). Bodily condition consisted of an immersive VR setup to engage self-motion cues, vision only condition consisted of passive navigation without interaction, in the interactive allocentric map condition patients could use a bird-view map, in the reduced executive load condition directional cues and attentional markers were employed, and during free navigation no aid was implemented. Bodily condition improved spatial memory compared to vision only and free navigation without cues. In addition, the interactive allocentric map was superior to the free navigation without cues. Surprisingly, the reduced executive load was comparable to vison only condition. Moreover, a detrimental impact of free navigation was observed on allocentric memory across testing trials. These findings challenge the notion of an amodal representation of space in aging, suggesting that spatial maps can be influenced by the modality in which the environment was originally encoded.

Relationship between prevalence of cardiometabolic diseases, self-reported memory loss, and self-reported depressed mood of older adults in Korea according to frailty and physical activity status

As the older population increases worldwide, frailty is the area of research that deserve further investigation and is considered a major social and public health concern. Frailty appears physically and mentally, and recently, the term cognitive frailty has been used to combine physical frailty and mild cognitive impairment syndrome. Frailty in older adults is characterized by low physical activity levels and a sedentary lifestyle. Physical activity is essential in managing mental health issues such as depression and can improve the executive function and memory of older adults with mild cognitive impairment. Therefore, this study aimed to examine the prevalence of cardiometabolic diseases, self-reported memory loss, and depression among older adults in Korea according to frailty and physical activity status. Using data from the 2019 Korea National Health and Nutrition Survey, this study analyzed 613 community-dwelling older males aged ≥65 years. Physical activity was measured using a Global Physical Activity Questionnaire. A health-related quality of life instrument with eight items (HINT-8) was used to assess self-reported memory loss and depressed mood. Relationships between physical activity levels, self-reported memory loss and depressed mood were analyzed using logistic regression. The incidence of HINT-8 memory (0.52 (95% confidence interval (CI): 0.32–0.85)) was significantly lower in the Physical Activity Level (PAL)-high/pre-frail; the incidence of HINT-8 depression (0.35 (95% CI: 0.21–0.59); 0.29 (95% CI: 0.17–0.52)) was significantly lower in the and PAL-high/pre-frail. We verified that the group with PAL-low/frail had the highest self-reported memory loss and depressed mood, suggesting that more physical activity may reduce self-reported memory loss and depressed mood among frail older males in Korea. However further research is needed to analyze the level of physical activity separately between work and leisure.

Impact of COVID‐19 infection on the cognition and emotion of Peruvians: analysis after 6‐12 months post‐infection

AbstractBackgroundCOVID‐19 pandemic significantly impacted different systems and organs (cardiovascular, metabolic, immune, brain, and others). More than two years after the first wave of COVID‐19 in Peru, we still do not know the consequences on cognition and emotion, and nowadays, different studies suggest the impact of COVID‐19 might trigger mild cognitive impairment, dementia, and neuropsychiatric syndromes in the future.MethodsAn ex‐post facto study was carried out with two groups, considering a neurocognitive evaluation (general cognition, verbal fluency, attention, and executive function) and emotion (depression, anxiety, and stress) and performed between 6 and 18 months after the first confirmed diagnosis of COVID‐19 in Peruvians (by PCR or antigen test). The mean age was 37.03 ± 15.57 (age range between 17 and 86 years old), and 60.5% were Female. We use the following instruments: INECO Frontal screening, Addenbrooke’s Cognitive Examination‐Revisado (ACE‐R), Verbal Fluency, TMT A/B, and DASS‐21.ResultsNo specific differences in general cognition were found. However, we found an effect in the INECO Frontal Screening (IFS) and the DASS‐21 (Anxiety scale). Patients diagnosed with COVID‐19 by PCR or antigen test have a slightly reduced frontal function (executive function).ConclusionsCOVID‐19 impacted high hierarchical frontal functions, but these effects are not well identified with general cognitive testing. Similarly, an increase in anxiety was found. More specific evaluation and sensitive techniques are needed to elucidate future COVID‐19 consequences on brain function.

Apathy as a Predictor of Motoric Cognitive Risk Syndrome

AbstractBackgroundApathy is a psychological syndrome, characterized by lack of motivation and interest, flattening of affect, and social withdrawal; that predicts cognitive decline including dementia. Current literature highlights apathy as a separate entity from depression, which is uniquely correlated to cognitive and functional decline in neurologic diseases like stroke and Parkinson’s Disease as well as in community dwelling‐older adults. Further, apathy may mediate the previously described association between depression and cognitive/functional decline. Our objectives were to 1) investigate the association between apathy at baseline and incident predementia syndromes including mild cognitive impairment (MCI) and motoric cognitive risk syndrome (MCR) and 2) explore the direct and indirect relationships of apathy and motoric cognitive outcomes.MethodWe prospectively studied the association between apathy (3‐item subscale of the Geriatric Depression Scale) and incident predementia syndromes in 542 community‐dwelling older adults enrolled in the Central Control of Mobility in Aging study, using Cox proportional hazard models. Associations were reported as hazard ratio (HR) with 95% confidence intervals (CIs), adjusting for age, education, baseline cognitive performance, and dysphoria. In a subset of 347 participants, we examined the mediating role of cytokines on the association between apathy and gait velocity in linear regression models at cross section. We also looked at the mediating role of apathy on the association between dysphoria and multimorbidity and gait velocity.ResultApathy was associated with incident MCR (HR 2.39, 95% CI: 1.10‐5.20), but not MCI. Linear regression models showed that Interleukin‐6 (Il‐6), but not C‐Reactive Protein was significantly associated with apathy adjusted for age, gender, and years of education (B = 0.037, 95% CI: 0.002–0.072, p = 0.04). Apathy was associated with a slower gait velocity (B = 14.45, 95% CI: 24.89–4.01, p = 0.01), cross sectionally. Mediation analyses demonstrated that IL‐6 modestly mediates the relationship between apathy and gait velocity. Additionally, apathy mediated the relationships between dysphoria and multimorbidity and gait velocity.ConclusionOverall, our findings indicate that apathy may be an early predictor of motoric cognitive decline, which precedes predementia syndromes. Inflammation plays a modest role, but the underlying biology of apathy warrants further investigation.

ЦЕРЕБРОВАСКУЛЯРНАЯ ПАТОЛОГИЯ У ПАЦИЕНТОВ C ИШЕМИЧЕСКОЙ БОЛЕЗНЬЮ СЕРДЦА (РЕЗУЛЬТАТЫ НЕЙРОВИЗУАЛИЗАЦИИ)

Introduction. Cerebral microangiopathy associated with vascular risk factors makes a significant contribution to the deterioration of the morphological state of the brain. The aim of the study was to assess the neurological status and state of the brain in patients with stable coronary heart disease (CHD) who are treated in the cardiology department before coronary bypass surgery. Material and methods. 170 male patients, aged 58±6 years, were examined. Patients with a history of acute cerebrovascular accident, trauma and brain masses, carotid artery stenosis >50%, depression and dementia were not included. All of them underwent a neurological examination and testing according to the Mini Mental Status Assessment Scale (MSSS). The brain examination was performed on a multislice computed tomography (MSCT) Somatom Sensation 64, Siemens. In describing the results, the following were taken into account: the width of the ventricles of the brain (the age norm of the width of the third ventricle is <7 mm for persons under 60 years of age, and <9 mm - over 60 years of age), leukoaraiosis, cysts, signs of cortical atrophy, the ventriculocranial index 3 (VKI 3) was calculated - the ratio of the maximum width of the third ventricle to the greatest distance between the internal plates of the skull bones (age norms: persons 41-60 years old - 3.3%; 61-70 years old - 3.9%; over 70 years old - 4.3%). Standard methods of descriptive statistics were used. Results. After a neurological examination, it was found that the frequency of occurrence of vestibulopathy syndrome was 24%, asthenic syndrome - 56%, mild cognitive impairment syndrome - 46% (test results for KShOPS - 27 [26; 28] points). The identified neurological symptoms were accompanied by morphological changes in the brain tissues. The width of the third ventricle was 7.6 ± 2.0 mm, the IHF index was 3 - 4.2%, the number of patients with leukoaraiosis was 26%, with signs of cortical atrophy - 19% of patients. When comparing the obtained results of neuroimaging with the established age norms, it was found that, despite the fact that the average age of our patients did not exceed 60 years, the width of the third ventricle in them corresponded to the indicators of the age category of healthy people over 60 years old, and the values of the VKI 3 index corresponded to the age norms. for healthy subjects over 70 years of age. Conclusion. The data obtained indicate that asthenia, moderate cognitive disorders, disorders of the coordinating-motor sphere are very common in patients with coronary artery disease. Neuroimaging signs of cerebral microangiopathy (leukoareosis, expansion of cerebrospinal fluid spaces) indicate the vascular nature of the identified neurological disorders. Issues of progression of cerebrovascular pathology in this cohort of patients require further study.

Method of differential diagnosis of mild cognitive impairment of various origins: cross sectional study

INTRODUCTION:The differential diagnosis of mild cognitive impairment (MCI), due to the high prevalence in the population and the rapid increase in incidence, is an urgent task. The most common causes leading to the development of cognitive impairment are Alzheimer’s disease (AD), cerebrovascular pathology, and their combination. AD usually manifests as an amnestic type of mild cognitive impairment (aMCI) at the pre-dementia stage. Subcortical vascular mild cognitive impairment (svMCI) is considered as the prodromal stage of subcortical vascular dementia. According to the results of pathomorphological studies, it was found that subfields of the hippocampal formation are selective vulnerability to AD, ischemia/hypoxia, and aging.Currently, using the FreeSurfer 6.0 software, it is possible to obtain quantitative indicators of the hippocampal formation subfieldsin vivo.The current trend in medicine is the development and implementation of new diagnostic solutions based on artificial intelligence and machine learning. One of the machine learning algorithms is binary logistic regression, which we used in the course of the study for the differential diagnosis of MCI of various origins.OBJECTIVE:To develop a method for the differential diagnosis of mil cognitive impairment of various origins.MATERIALS AND METHODS:The study included patients with the syndrome of mild cognitive impairment who were examined in the department of geriatric psychiatry of the V.M.Bekhterev National Medical Research Center for Psychiatry and Neurology, from which two groups were formed: group 1 — patients with aMCI, group 2 — patients with svMCI. Conditionally healthy volunteers, comparable in age, sex and level of education, made up the 3rdgroup (control). MRI examination was performed using a Excelart Vantage Atlas XGV magnetic resonance imaging system (Toshiba, Japan) with a magnetic field strength of 1.5 T, followed by MR morphometry of the subfields of the hippocampal formation.Statistics:Statistical analysis was carried out using data that was converted from a database in Microsoft Excel to the statistical package IBM SPSS 21. To develop a differential diagnosis method, based on the data obtained, the binary regression method and ROC analysis were used.RESULTS:Based on the obtained MR-morphometry data, a method was developed using the binary logistic regression equation. The value of p≥0.5 makes it possible to classify the patient to the aMCI group, and the value of p<0.5 — to the svMCI. The sensitivity of the method is 90%, the specificity is 80%, and the accuracy is 85%.DISCUSSION:Using binary logistic regression, the selection of variants of sets of variables (quantitative indicators) was carried out, for which ROC curves were constructed. The selection criterion was the area under the ROC curve — the AUC criterion (Area Under the Curve). The largest area under the curve (AUC=0.824) in the differential diagnosis of aMCI from svMCI was determined for the combination of the volume of the left subiculum and the thickness of the right entorhinal cortex.Since patients in the aMCI group have a significantly lower number of vascular foci than in the svMCI group (p<0.05), at the next stage, one more variable, the volume fraction, was added to the selected combination of two variables (volume of the left subiculum and thickness of the right entorhinal cortex) hypointense foci. When conducting an ROC analysis with a combination of three variables, an increase in AUC to 0.892 was noted. Further, using a combination of three variables and a binary logistic regression equation, a method for differential diagnosis of aMCI from svMCI was developed.CONCLUSION:The method of differential diagnosis based on binary logistic regression using MR morphometry data allows to distinguish patients with aMCI from patients with svMCI with high sensitivity and specificity.

The concurrent impact of mild cognitive impairment and frailty syndrome in heart failure.

Pathological processes associated with ageing increase the risk of cognitive deficits and dementia. Frailty syndrome, also known as weakness or reserve depletion syndrome, may significantly accelerate these pathological processes in the elderly population. Frailty syndrome is characterized by decreased physiological function and neuropsychiatric symptoms, including cognitive decline and depressive states. In people with cardiovascular disease, the risk of frailty is 3 times higher. Frailty syndrome is particularly prevalent in severe heart failure, which increases the risk of mortality, increases hospital readmission, and reduces patients' quality of life. In addition, co-occurrence of cognitive impairment and frailty syndrome significantly increases the risk of dementia and other adverse outcomes, including mortality, in the heart failure population.

Usability of an Embodied CAVE System for Spatial Navigation Training in Mild Cognitive Impairment.

Individuals with mild cognitive impairment (MCI) usually report navigation and spatial memory impairments. Spatial navigation is an embodied process that requires the active involvement of both physical (e.g., motor commands and proprioception) and cognitive (e.g., decision-making and mental rotation) information. Immersive virtual reality (IVR) is a valuable tool that employs this information as real-world navigation does. Given the crucial impact of spatial navigation on daily life, research should focus on ways to enhance it. Though they are still in their development, contemporary IVR methods for spatial navigation training in MCI seem promising. In this usability study, eight patients with MCI syndrome tested an IVR spatial navigation training demo and interacted with the CAVE using active stereo glasses, a foot-motion pad, and a joypad. During the demo, users were asked to report their impressions on the IVR training using the thinking-aloud procedure. Moreover, questionnaires regarding usability, presence and cybersickness were administered at the end of the experience. Our results show that the first version of this system is usable by the patients even if most of them did not have experience with PC/IVR. The system provided a moderate sense of spatial presence and limited negative effects. Issues found during the thinking-aloud procedure concerned the visual aspects, which affected the interaction user-system. Participants reported that they needed more practice with the foot-motion pad even though the overall experience was positively evaluated. Identifying these critical features was essential to develop an improved version of the current system.

Predicting amyloid PET and tau PET stages with plasma biomarkers.

Staging the severity of Alzheimer's disease pathology using biomarkers is useful for therapeutic trials and clinical prognosis. Disease staging with amyloid and tau PET has face validity; however, this would be more practical with plasma biomarkers. Our objectives were, first, to examine approaches for staging amyloid and tau PET and, second, to examine prediction of amyloid and tau PET stages using plasma biomarkers. Participants (n = 1136) were enrolled in either the Mayo Clinic Study of Aging or the Alzheimer's Disease Research Center; had a concurrent amyloid PET, tau PET and blood draw; and met clinical criteria for cognitively unimpaired (n = 864), mild cognitive impairment (n = 148) or Alzheimer's clinical syndrome with dementia (n = 124). The latter two groups were combined into a cognitively impaired group (n = 272). We used multinomial regression models to estimate discrimination [concordance (C) statistics] among three amyloid PET stages (low, intermediate, high), four tau PET stages (Braak 0, 1-2, 3-4, 5-6) and a combined amyloid and tau PET stage (none/low versus intermediate/high severity) using plasma biomarkers as predictors separately within unimpaired and impaired individuals. Plasma analytes, p-tau181, Aβ1-42 and Aβ1-40 (analysed as the Aβ42/Aβ40 ratio), glial fibrillary acidic protein and neurofilament light chain were measured on the HD-X Simoa Quanterix platform. Plasma p-tau217 was also measured in a subset (n = 355) of cognitively unimpaired participants using the Lilly Meso Scale Discovery assay. Models with all Quanterix plasma analytes along with risk factors (age, sex and APOE) most often provided the best discrimination among amyloid PET stages (C = 0.78-0.82). Models with p-tau181 provided similar discrimination of tau PET stages to models with all four plasma analytes (C = 0.72-0.85 versus C = 0.73-0.86). Discriminating a PET proxy of intermediate/high from none/low Alzheimer's disease neuropathological change with all four Quanterix plasma analytes was excellent but not better than p-tau181 only (C = 0.88 versus 0.87 for unimpaired and C = 0.91 versus 0.90 for impaired). Lilly p-tau217 outperformed the Quanterix p-tau181 assay for discriminating high versus intermediate amyloid (C = 0.85 versus 0.74) but did not improve over a model with all Quanterix plasma analytes and risk factors (C = 0.85 versus 0.83). Plasma analytes along with risk factors can discriminate between amyloid and tau PET stages and between a PET surrogate for intermediate/high versus none/low neuropathological change with accuracy in the acceptable to excellent range. Combinations of plasma analytes are better than single analytes for many staging predictions with the exception that Quanterix p-tau181 alone usually performed equivalently to combinations of Quanterix analytes for tau PET discrimination.

The Learning of Memory Support System in Individuals with Mild Cognitive Impairment

AbstractBackgroundThe syndrome of mild cognitive impairment (MCI) is classified into different subtypes– amnestic MCI (aMCI) and non‐amnestic MCI based on cognitive domains impacted, while different underlying disease etiologies cause the impairments. The Memory Support System (MSS), a memory‐support tool which utilizes a calendar/planner, has been shown to have positive impact on daily functioning in MCI (Chandler et al., 2017). We have previously shown that cognitive impairment severity and personality traits are associated with MSS learning (De Wit et al., 2021; Khayoun et al., 2021). In this study, we hypothesized that 1) participants with single domain aMCI (SD‐aMCI) will have higher MSS learning scores than multi‐domain aMCI (MD‐aMCI), and 2) participants with suspected Alzheimer’s disease (AD) etiology will have lower MSS learning scores than other etiologies.MethodParticipants (mean age = 75.2) underwent daily MSS training between 2017 and 2021 as part of the 10‐day Mayo Clinic HABIT program. The MSS learning success score (LSS) was determined by how far participants progressed in three learning phases of increasing difficulty: Acquisition (0‐2 points), Application (3‐4 points), and Adaptation (5‐6 points; Greenway et al., 2008). Ordinal logistic regression analysis was used to predict MSS learning scores between SD‐aMCI (n = 142) versus MD‐aMCI (n = 119), and AD etiology (n = 213) versus other neurodegenerative etiologies (n = 57). Dementia Rating Scale‐2 scores (Jurica, 2001) were included to control for cognitive severity.ResultCompared to participants with SD‐aMCI, those with MD‐aMCI had 54.1% lower odds of having higher LSS at training end (p = .004), after controlling for cognitive impairment severity. AD versus other etiology’s impact on LSS was nonsignificant.ConclusionParticipants with MD‐aMCI showed poorer MSS learning efficiency than participants with SD‐aMCI. Etiology did not impact MSS learning. Results suggest having more than just memory impairment (e.g., additional language or executive dysfunction) reduces MSS learning, regardless of overall impairment level. Additional MSS training may be needed to facilitate learning for these individuals.

Cross‐Validation of a Novel Apathy Measurement Model in a Diverse Ambulatory Cohort of Older Adults with Memory Complaints

AbstractBackgroundApathy is a psychological syndrome characterized by a loss of motivation, goal‐directed activity, and diminished emotion (Marin, 1990), which may mediate the relationship between depression and cognitive impairment (Funes et al., 2018) and be an early risk factor for dementia that precedes predementia syndromes including non‐amnestic mild cognitive impairment (NA‐MCI) and motoric cognitive risk syndrome (MCR) (Ceïde et al., 2020). While there is no gold standard measure of apathy, assessment tools vary from subscales of depression instruments to apathy specific questionnaires. Our group conducted a confirmatory factor analysis (CFA) of the Geriatric Depression Scale (GDS) in a pooled cohort of community and memory clinic older adults which identified a novel 2‐factor model that distinguishes apathy from depression. The goal of this study was to cross‐validate this novel apathy measurement model in a bilingual urban primary care clinical cohort.MethodWe conducted a CFA in the primary care cohort that was composed of participants from the 5‐Cog Battery for Detecting Cognitive Impairment and Dementia clinical trial. We compared the reliability measures and model fit indices of both the previous 2‐factor model and this novel model. Cohort characteristics were compared as well.ResultThe primary care clinical cohort was significantly different from the community and memory clinic cohorts in all baseline characteristics. The CFA of the primary care cohort yielded depression and apathy factors with good reliability (α = .78 and .63, respectively). Despite the fact that the primary care cohort included Spanish speakers, it performed similarly to the reliability of the depression and apathy factors in the community dwelling and memory clinic pooled cohort (α = .75 and .63, respectively). Both the primary care and memory clinic cohorts had higher depression and apathy scale scores compared to the community dwelling cohort, with the primary care cohort scoring in between the community and memory clinic cohorts in both depression and apathy scale measurements.ConclusionOur 2‐factor measurement model demonstrated similar reliability and fit across 3 distinct cohorts (community dwelling, memory clinic and primary care clinic) and 2 languages (English and Spanish), indicating its appropriateness as an apathy measurement model in further clinical trials.

Smart Brain Care – A novel approach to health care of mild cognitive impairment and mild dementia

Abstract Background Dementia is a huge burden. Trends for the aging European nations indicate a significant increase of people with dementia. Prevention and early detection are the key elements to reduce risk factors and to treat reversible causes. In addition, identifying people at the beginning of the disease process is crucial when disease-modifying therapy becomes available. Methods We aim to develop a complex intervention to improve the identification, diagnosis, and treatment of people with mild cognitive impairment (MCI) and mild dementia syndromes. Our goal is to reduce the time to diagnosis, raising awareness for MCI and increase patient involvement. First, barriers in pathways of care are determined in a systematic review and refined by conducting focus groups and interviews with primary care physicians (PCPs), specialists and experts in the field. A first theory about intervention components and how they interact are developed and will be further tested and adapted through development phase, feasibility and piloting. Results The first blueprint of Smart Brain Care addresses three identified key barriers for an improved care of MCI and mild dementia syndromes (communication, skills and awareness) by three interventions (1-3), all linked and accessible through an e-database: An online platform (1) for exchange between PCPs, specialists and experts, (2) a screening tool, diagnosis-algorithm and training for PCPs as well as (3) information materials (e.g., fact sheets, short videos) separately accessible for patients. Conclusions There is still low awareness about MCI under health care providers and the general population. A lack of knowledge, cooperation strategies and guidance seem to play an important role for the management of MCI and mild dementia syndromes. Key messages • We need to increase focusing on the identification of people with MCI and mild dementia syndromes. • Call for a structured diagnosis and treatment regimen to support primary care physicians as key players in the management of MCI and mild dementia syndromes.

Language performance as a prognostic factor for developing Alzheimer's clinical syndrome and mild cognitive impairment: Results from the population-based HELIAD cohort.

There is limited research on the prognostic value of language tasks regarding mild cognitive impairment (MCI) and Alzheimer's clinical syndrome (ACS) development in the cognitively normal (CN) elderly, as well as MCI to ACS conversion. Participants were drawn from the population-based Hellenic Longitudinal Investigation of Aging and Diet (HELIAD) cohort. Language performance was evaluated via verbal fluency [semantic (SVF) and phonemic (PVF)], confrontation naming [Boston Naming Test short form (BNTsf)], verbal comprehension, and repetition tasks. An additional language index was estimated using both verbal fluency tasks: SVF-PVF discrepancy. Cox proportional hazards analyses adjusted for important sociodemographic parameters (age, sex, education, main occupation, and socioeconomic status) and global cognitive status [Mini Mental State Examination score (MMSE)] were performed. A total of 959 CN and 118 MCI older (>64 years) individuals had follow-up investigations after a mean of ∼3 years. Regarding the CN group, each standard deviation increase in the composite language score reduced the risk of ACS and MCI by 49% (8-72%) and 32% (8-50%), respectively; better SVF and BNTsf performance were also independently associated with reduced risk of ACS and MCI. On the other hand, using the smaller MCI participant set, no language measurement was related to the risk of MCI to ACS conversion. Impaired language performance is associated with elevated risk of ACS and MCI development. Better SVF and BNTsf performance are associated with reduced risk of ACS and MCI in CN individuals, independent of age, sex, education, main occupation, socioeconomic status, and MMSE scores at baseline.

Discriminating Aging Cognitive Decline Spectrum Using PET and Magnetic Resonance Image Features.

The population aging increased the prevalence of brain diseases, like Alzheimer's disease (AD). Early identification of individuals with higher odds of cognitive decline is essential to maintain quality of life. Imaging evaluation of individuals at risk of cognitive decline includes biomarkers extracted from brain positron emission tomography (PET) and structural magnetic resonance imaging (MRI). We propose investigating ensemble models to classify groups in the aging cognitive decline spectrum by combining features extracted from single imaging modalities and combinations of imaging modalities (FDG+AMY+MRI, and a PET ensemble). We group imaging data of 131 individuals into four classes related to the individuals' cognitive assessment in baseline and follow-up: stable cognitive non-impaired; individuals converting to mild cognitive impairment (MCI) syndrome; stable MCI; and Alzheimer's clinical syndrome. We assess the performance of four algorithms using leave-one-out cross-validation: decision tree classifier, random forest (RF), light gradient boosting machine (LGBM), and categorical boosting (CAT). The performance analysis of models is evaluated using balanced accuracy before and after using Shapley Additive exPlanations with recursive feature elimination (SHAP-RFECV) method. Our results show that feature selection with CAT or RF algorithms have the best overall performance in discriminating early cognitive decline spectrum mainly using MRI imaging features. Use of CAT or RF algorithms with SHAP-RFECV shows good discrimination of early stages of aging cognitive decline, mainly using MRI image features. Further work is required to analyze the impact of selected brain regions and their correlation with cognitive decline spectrum.

Olfactory Dysfunction and Incidence of Motoric Cognitive Risk Syndrome: A Prospective Clinical-Pathologic Study.

To examine associations between olfactory dysfunction, Alzheimer disease (AD) pathology, and motoric cognitive risk syndrome (MCR), a predementia syndrome characterized by cognitive complaints and slow gait that is associated with risk for AD and other dementias. We conducted a retrospective analysis of a prospective cohort study to examine whether baseline olfactory function was associated with the risk of incident MCR in 1,119 adults aged 60 years and older (75.1% female). The association between performance on the Brief Smell Identification Test (BSIT) and incident MCR risk was computed using Cox models and reported as the hazard ratio (HR) with 95% CIs adjusted for demographic, comorbidity, and cognitive factors. Furthermore, we assessed the relationship between postmortem AD pathology and non-AD pathology and olfactory function at the time of MCR diagnosis using linear regression models adjusted for sex, education, age at death, and time from diagnosis to death. There were 544 (48.6%) incident cases of MCR over a median follow-up of 3.94 years. Lower BSIT scores (poor olfaction) at baseline were associated with an increased risk of incident MCR (HR for a 1-point increase in BSIT score 0.92; 95% CI 0.88-0.96) in fully adjusted models. Those with hyposmia (scores of ≤8 on the BSIT) at baseline (26.6%) were at an increased risk of MCR (HR 1.44; 95% CI 1.19-1.74) compared with those with normal olfactory function. Higher levels of the composite measure of global AD pathology and presence of Lewy body pathology were associated with lower BSIT scores at the time of incident MCR diagnosis (n = 118). τ tangle density, a specific component of AD pathology, was inversely associated with olfactory function, and the correlation remained after controlling for mild cognitive impairment syndrome and the presence of Lewy body pathology. The results provide evidence that olfactory dysfunction precedes MCR incidence and is related to Alzheimer pathology, providing a clinical approach to risk stratify and subtype MCR.

Risk of Alzheimer’s disease in patients with the syndrome of mild cognitive impairment, amnestic type (cluster analysis)

IntroductionThe creation of mathematical models for determining the risk of Alzheimer’s disease in patients with mild cognitive impairment based on immune markers of blood is important for differential diagnosis of AD, assessment of the clinical state of patients at different stages of the disease, and optimization of therapy.ObjectivesTo assess the risk of AD in patients with amnestic type of mild cognitive impairment (aMCI) with the use of such markers of inflammation as enzymatic activity of leukocyte elastase (LE) and the functional activity of α1-proteinase inhibitor (α1-PI).MethodsThe object of mathematical analysis on the basis of cluster analysis and logistic regression was the database, including the results of the above immunological parameters (enzyme activity of LE and functional activity of α1-PI.) in plasma of 78 patients with aMCI receiving outpatient treatment in the clinic of FSBSI “Mental Health Research Centre”. Among the examined patients there were 25 men and 53 women aged 44 to 89 years (69.1 ± 9.95).ResultsClustering by k-means and classification by logistic regression indicate the risk of developing AD in patients with aMCI depending on the activity of LE and α1-PI in blood plasma. The total coincidence of objects included in the clusters and in the AD risk group was 94%.ConclusionsThe high coincidence of the two different methods of grouping confirms the previously stated position on the possibility of identifying patients with a high risk of AD among patients with aMCI in the activity of LE and α1-PI in the blood of patients.DisclosureNo significant relationships.

Інновації в стратегії фармакотерапії ранніх стадій когнітивних розладів

Стаття присвячена проблемі корекції когнітивних розладів, що супроводжують порушення мозкового кровообігу. Наголошено, що застосування адекватної фармакопрофілактичної стратегії при синдромі помірних когнітивних розладів більш ефективне, ніж при клініці деменції, що вже маніфестувала. Провідним компонентом такої стратегії є вплив на фундаментальні нейромедіаторні механізми розвитку цього синдрому — холін-, ГАМК- та дофамінергічні. До останнього часу в неврологічній практиці комбіновані препарати були представлені, як правило, або полікомпонентними рослинними седативними засобами, або комбінацією двох ноотропних складових, що далеко не завжди дозволяла забезпечити клінічний вплив на всі ланки патогенезу синдрому. Нещодавно в Україні з’явився принципово новий, інноваційний комбінований препарат (Когніфен), що містить у своєму складі два абсолютно різні за хімічною структурою та фармакологічними властивостями компоненти, які оптимально доповнюють один одного із точки зору клініко-фармакологічних ефектів, — фенібут (300 мг) та іпідакрин (5 мг). Появу Когніфену можна розглядати як новий етап у розвитку клінічної нейрофармакології та фармакотерапії когнітивних розладів на ранніх стадіях.

Стратегия мембранопротекции в фармакотерапии сосудистых когнитивных расстройств

В статье представлены современные взгляды на проблему сосудистой когнитивной дисфункции, в частности, на природу и возможности лечения синдрома умеренных когнитивных расстройств как одной из самых распространенных форм когнитивной недостаточности у лиц пожилого и старческого возраста. С этой точки зрения проанализированы требования к выбору оптимального инструмента фармакотерапии и фармакопрофилактики указанного синдрома, прежде всего стратегии мембранопротекции. Особое внимание при этом уделено механизмам действия и особенностям клинического применения препарата Лира (цитиколин) — средства с уникальными клинико-фармакологическими свойствами, которые позволяют реализовать стратегию патогенетически обоснованной нейро- и геропротекторной фармакотерапии при нарушениях мозгового кровообращения. Подробно рассмотрены механизмы действия, клиническая эффективность Лиры (цитиколина), характеристики безопасности и рекомендации по практическому применению препарата.