Severity Of Cognitive Decline Research Articles

Factors Influencing the Development and Severity of Cognitive Decline in Patients with Chronic Heart Failure

Background and Objectives: Considering the increasing prevalence of chronic heart failure (CHF) and cognitive decline (CD) observed in recent decades and the complex interrelation between these two pathologies often encountered in the same patient, in this study, we aimed to highlight the connection between CHF, defined as recommended by the European Society of Cardiology guidelines, and CD, evaluated by employing five neuropsychological scales. Materials and Methods: Our study was conducted on 190 patients with very high cardiovascular risk profiles admitted between 5 September 2021 and 15 November 2023 in the Municipal Emergency Hospital Timisoara. Of these, 103 had CHF (group A) and 87 did not (group B). Results: Although similar concerning age, sex distribution, and risk factors (excepting lipid profile), patients from group A had lower Mini Mental State Evaluation (MMSE) and Montreal Cognitive Assessment (MoCA levels (p = 0.003, respectively, p = 0.017) scores, more reduced daily activity (p = 0.021), and more severe depression (p = 0.015) compared to group B. We documented statistically significant correlations between left-ventricular ejection fraction (LVEF) and the levels of N-terminal pro–B-type natriuretic peptide (NT-pro-BNP), as well as with the results of MMSE (r = 0.226, p = 0.002 and r = −0.275, p = 0.005, respectively), daily activity, and depression (p ˂ 0.001). Multi-logistic regression models indicated age, blood pressure values, decreased daily activity, and depression as risk factors for CD in patients with CHF. Conclusions: In patients with CHF, there is an increased propensity of CD, with a direct relationship between MMSE and LVEF levels and an indirect one between MMSE and NT-pro-BNP levels. The concomitance of depression and reduced activity levels are aggravating CD in these patients.

The collaborative cross mouse for studying the effect of host genetic background on memory impairments due to obesity and diabetes.

Over the past few decades, a threefold increase in obesity and type 2 diabetes (T2D) has placed a heavy burden on the health-care system and society. Previous studies have shown correlations between obesity, T2D, and neurodegenerative diseases, including dementia. It is imperative to further understand the relationship between obesity, T2D, and cognitive deficits. This investigation tested and evaluated the cognitive impact of obesity and T2D induced by high-fat diet (HFD) and the effect of the host genetic background on the severity of cognitive decline caused by obesity and T2D in collaborative cross (CC) mice. The CC mice are a genetically diverse panel derived from eight inbred strains. Our findings demonstrated significant variations in the recorded phenotypes across different CC lines compared to the reference mouse line, C57BL/6J. CC037 line exhibited a substantial increase in body weight on HFD, whereas line CC005 exhibited differing responses based on sex. Glucose tolerance tests revealed significant variations, with some lines like CC005 showing a marked increase in area under the curve (AUC) values on HFD. Organ weights, including brain, spleen, liver, and kidney, varied significantly among the lines and sexes in response to HFD. Behavioral tests using the Morris water maze indicated that cognitive performance was differentially affected by diet and genetic background. Our study establishes a foundation for future quantitative trait loci mapping using CC lines and identifying genes underlying the comorbidity of Alzheimer's disease (AD), caused by obesity and T2D. The genetic components may offer new tools for early prediction and prevention.

Analysis of cognitive dysfunction in Parkinson's disease using voxel based morphometry and radiomics.

Cognitive impairment in Parkinson's disease (PD) is associated with changes in the brain anatomical structures. The objective of this study, is to identify the atrophy patterns based on the severity of cognitive decline and evaluate the disease progression. In this study, gray matter alterations are analysed in 135 PD subjects under 3 cognitive domains (91 Cognitively normal PD (NC-PD), 25 PD with Mild Cognitive Impairment (PD-MCI) and 19 PD with Dementia (PD-D)) by comparing them with 58 Healthy Control (HC) subjects. Voxel Based Morphometry (VBM) is used to segment the gray matter regions in magnetic resonance images and analyse the atrophy patterns statistically. Significant patterns of gray matter variations observed in the middle temporal and medial frontal region differentiate between HC and PD subject groups based on the severity of cognitive decline. Abnormalities in gray matter is substantiated through radiomic features extracted from the significant gray matter clusters. Significant radiomic features of the clusters are able to differentiate between the HC and PD-D subjects with an accuracy of 81.82%. Higher atrophy levels identified in PD-D subjects compared to NC-PD and PD-MCI group enables early diagnosis and treatment procedures. The combined and comprehensive analysis of gray matter alterations through VBM and radiomic features gives better assessment of cognitive impairment in PD.

Examining the Driving Habits of Older Canadians as Captured by the COMPASS‐ND Study

AbstractBackgroundDriving is associated with a sense of autonomy and good quality of life in older adults. However, older adults often change their driving habits, such as regulating how often, how far, and under what conditions (e.g., time of day, weather) they drive, in part due to changes in cognition. Our study describes data from the first large‐scale Canadian cohort study to investigate differences in driving habits across cognitive groups, including cognitively healthy older adults (control), Subjective Cognitive Decline (SCD), Mild Cognitive Impairment (MCI), and Alzheimer’s Disease (AD).MethodWe analyzed data from the Comprehensive Assessment of Neurodegeneration and Dementia study (COMPASS‐ND, Chertkow et al., 2019), a population‐based study of Canadians with various cognitive and functional abilities (May 2021 Data Release). The final sample analyzed included 317 participants (55% Females, Meanage = ∼72). We report the responses for the following driving‐related questions: licensing status (no longer have license, drive with or without restrictions), driving frequency, driving distance, and driving restrictions (e.g., bad weather).ResultMost participants across all groups reported that they have a driver’s license without restrictions, including the AD group (AD: ∼61%, remaining groups: >90%). The following analyses only included current drivers. In terms of the frequency of driving and the distance travelled, as expected, the AD group drove the least often and the shortest distances. The most frequent restriction types selected by all groups were bad weather and nighttime driving. The number of restriction types increased with the severity of cognitive decline. Interestingly, driving restrictions reported by the SCD group more closely approximated the cognitively impaired groups (MCI and AD) than the control group.ConclusionAlthough many of the AD group participants still had a license, they also reported the greatest number of driving restrictions. Further, the SCD group and MCI group were quite similar in their responses for several items, indicating that even SCD may be associated with differences in driving habits. Implications of driving‐related limitations include reduced independence, socialization, participation, and access to resources (e.g., medical care, groceries).

GWAS identifies genetic factors associated with severity of cerebral amyloid angiopathy pathology

AbstractBackgroundCerebral amyloid angiopathy (CAA) commonly co‐occurs with Alzheimer’s disease (AD) pathologies, leading to an increased risk and severity of cognitive decline. While CAA is known to impact cognitive impairment, the genetics of CAA are not well understood, and most previous sample sizes have been small. To address this gap, we conducted a genome‐wide association study (GWAS) of CAA pathology to identify genetic factors that are associated with this understudied AD‐related amyloidosis.MethodWe utilized data from 6,038 autopsied and genotyped individuals from the National Alzheimer’s Coordinating Centers (NACC) who were evaluated for CAA pathology upon autopsy. Participants were age 50+ at death and non‐Hispanic white. Genetic data were available from SNP arrays imputed to TOPMed and analyses were conducted only on common variants (MAF >0.01). GWAS performed ordinal logistic regression to determine the effects of genetic variants on CAA pathology (coded as 0, none; 1, mild; 2, moderate; 3, severe). Models adjusted for sex, age at death, and the first three genetic principal components (PC‐AiR; GENESIS; R v4.2). We then meta‐analyzed across the cohorts (METAL).ResultWe observed genome‐wide significant associations with CAA severity at established AD loci, including APOE (top SNP: rs429358, MAF = 0.155, P = 1.6E−86) and BIN1 (top SNP: rs6733839, MAF = 0.397, P = 3.9E−08). We observed a novel association with CAA pathology on chromosome 9 (top SNP: rs10908023, MAF = 0.258, P = 4.3E−11).ConclusionThis is the largest study to date aimed at identifying genetics factors associated with CAA pathology. Our findings offer new insights into the genetics of CAA, a common player in the AD landscape. We acknowledge the need for a larger dataset and are now expanding the study by sample size and by including additional ADRD phenotypes to gain a better understanding of the full spectrum AD/ADRD. Continuing to uncover the genetic underpinnings of CAA could potentially help us think about AD treatment in new ways and mitigate the negative side‐effects of brain swelling and bleeding that have been observed in recent clinical trials.

Altered Callosal Morphology and Connectivity in Asymptomatic Carotid Stenosis.

Carotid stenosis, even in the clinically asymptomatic stage, causes cognitive impairment, silent lesions, and hemispheric changes. The corpus callosum (CC) is crucial for hemispheric cortical integration and specialization. To examine if CC morphology and connectivity relate to cognitive decline and lesion burden in asymptomatic carotid stenosis (ACS). Retrospective, cross-sectional. 33 patients with unilaterally severe (70%) ACS and 28 demographically and comorbidity-matched controls. A publicly available healthy adult lifespan (ages between 18 and 80; n = 483) MRI dataset was also included. A 3.0 T; T1 MPRAGE and diffusion weighted gradient echo-planar imaging sequences. Structural MRI and multidomain cognitive data were obtained. Midsagittal CC area, circularity, thickness, integrity, and probabilistic tractography were calculated and correlated with cognitive tests and white matter hyperintensity. Fractional anisotropy, mean diffusivity (MD), and radial diffusivity were determined from DTI. Independent two-sample t-tests, χ2 tests, Mann-Whitney U, locally weighted scatterplot smoothing (LOWESS) curve fit, and Pearson correlation. A P value < 0.05 was considered statistically significant. Patients with ACS demonstrated significant reductions in callosal area, circularity, and thickness compared to controls. The callosal atrophy was significantly correlated with white matter hyperintensity size (r = -0.629, P < 0.001). Voxel-wise analysis of diffusion measures in the volumetric CC showed that ACS patients exhibited significantly lower fractional anisotropy and higher MD and radial diffusivity in the genu and splenium of the CC than controls. Further lifespan trajectory analysis showed that although the midsagittal callosal area, circularity, and thickness exhibited age-related decreases, the values in the ACS patients were significantly lower in all age groups. Midsagittal callosal atrophy and connectivity reflect the load of silent lesions and the severity of cognitive decline, respectively, suggesting that CC degeneration has potential to serve as an early marker in ACS. 3 TECHNICAL EFFICACY STAGE: 2.

Increase of ALCAM and VCAM-1 in the plasma predicts the Alzheimer's disease.

Cell adhesion molecules (CAM) are crucial in several pathological inflammation processes in Alzheimer's disease (AD). However, their potential for clinical diagnostics remains unknown. The present investigation evaluated the clinical significance of ALCAM, VCAM-1, NCAM, and ICAM-1 levels in the plasma of participants with cognitive impairment (44 patients with mild cognitive impairment, 71 patients with Alzheimer's dementia, and 18 patients with other dementia) and 28 controls with normal cognitive ability. We also detected plasma levels of multiple inflammatory factors (IFN-gamma, IL-18, IL-1beta, IL-13, IL-8, IL-7, CCL11, MCP-1, TSLP, IL-10, BDNF, IL-17, IL-5, TREM-1) using Multiplex liquid chip and plasma levels of Abeta1-42 and Abeta1-40 using liquid-phase flow cytometry (FCM). Our findings demonstrated a correlation of ALCAM and VCAM-1 with age, the severity of cognitive decline, and MTA, but no significant difference between groups for NCAM and ICAM-1. ALCAM and VCAM-1 both demonstrated a positive correlation with the degree of atrophy in the medial temporal lobe structure. Further analysis revealed no significant correlation in plasma between VCAM-1, ALCAM and Abeta1-40, Abeta1-42. Nevertheless, there was a significant correlation between VCAM-1, ALCAM and many inflammatory factors. Furthermore, the predictive value of ALCAM and VCAM-1 for AD was assessed using a multi-parameter regression model. ALCAM and VCAM-1 in combination with ApoE4, education, age, and MMSE could predict AD with high precision (AUC=0.891; AIC=146.9) without imaging diagnosis. ALCAM and VCAM-1 combination improved the predictive accuracy significantly. In a nutshell, these findings revealed ALCAM and VCAM-1 as reliable indicators of Alzheimer's disease.

Does cognitive reserve or brain maintenance explain heterogeneity in episodic memory trajectories in late middle age?

AbstractBackgroundAging‐related episodic memory (EM) decline and Alzheimer’s disease (AD)‐related brain changes begin in late middle age around age 60. However, rate and severity of cognitive decline do not consistently correspond to the extent of neuropathological changes, suggesting a high degree of heterogeneity in EM trajectories. We tested if brain maintenance (BM; relative absence of changes in neural resources as a determinant of preserved cognition) and/or cognitive reserve (CR; a property of the brain that allows for sustained cognitive performance in the face of age‐related changes and brain insult or disease) explain individual differences and heterogeneity in EM in late middle age.MethodParticipants were 1604 men from the Vietnam Era Twin Study of Aging. A practice effect‐adjusted composite EM score based on six measures was calculated at three time points with mean ages of 56, 62, and 68. Young adult general cognitive ability (GCA) and lifetime years of education were used as proxy measures of CR. BM was assessed as relative change (from age 56 to 68) in cortical thickness and surface area in a bilateral cortical signature of AD regions‐of‐interest (N = 321). We used linear mixed effect modeling.ResultOn average, there was a significant decline in EM from age 56 to 68 (p&lt;0.001). Education (p = 0.042) and young adult GCA (p&lt;0.001) were positively related to EM, but there were no significant effects of education or GCA on the rate of EM change (all p’s≥0.316). Relative brain changes were not related to EM (all p’s≥0.067) and there were no significant interactions of CR proxies and brain changes on EM (all p’s≥0.379).ConclusionHigher education and higher young adult GCA were related to better EM performance across late middle age – with a stronger contribution of GCA compared to education – but EM change did not differ as a function of these proxy CR measures. Our results did not support effects of BM or CR on EM change in late middle age but rather reflected baseline differences in memory in those with low versus high education/cognitive ability. Whether differential change occurs at later ages or with increased AD pathology remains to be determined.

Brain‐wide spatial analysis reveals cell‐type‐specific genetic modifiers of Alzheimer’s disease progression

AbstractBackgroundThere is significant variation in the age at onset and severity of cognitive decline among those with Alzheimer’s disease (AD). Despite strong genetic links to AD loci, the specific variants, target genes and cell types that drive AD‐related deterioration remain elusive. Recent advances in brain‐wide cell type and pathology quantification across our AD mouse genetic reference panel provide new opportunities to identify genetic factors that act in a cell‐type‐specific fashion to modify disease progression in response to causal AD mutations; linking, for the first time, genetics to regional cell composition to characterize susceptibility versus resilience to AD.MethodImmunohistochemistry was completed to evaluate neurodegeneration(NeuN), gliosis(Iba1&amp;GFAP), and amyloid pathology(AB1‐42) in 250 mice from the AD‐BXD genetic reference panel. Using the QUINT workflow, hemibrain slices were systematically segmented and registered to the Allen Brain Atlas to gain a global perspective of percent cell/pathology coverage. The heritability of individual cell composition was calculated and quantitative trait loci(QTL) mapping was completed.ResultCompositional differences between the strains, particularly the BXD founder strains, became apparent when evaluating neurodegeneration and microglial proliferation. Despite comparable levels of amyloid, cortical and hippocampal NeuN and Iba1 coverage significantly varied among strains; however, this variation did not explain individual differences in short and long‐term memory capacity. Genetic mapping of individual cell composition traits identified a significant QTL associated with cortical neuron load (h = 0.6) on chromosome 17. Lrfn2 was identified as a gene of interest as it was differentially expressed between mice that had the BB vs BD genotype at the most significant variant location under the peak.ConclusionThis method of combining omics and imaging data to link changes in gene expression, cell composition, and behavior allows for the assessment of disease subtypes with the potential to aid the development of precision medicine solutions to AD. Specifically, changes in cell coverage can be associated with differences in gene expression among the AD‐BXD population to detect genes associated with regional cell composition. These candidates will be validated by creating cell‐type‐specific knock‐in or knock‐out models and measuring cognitive functioning to determine the effect of these genes on memory performance.

Exploring the Relationship Between Alzheimer’s Disease and Age-Related Hearing Loss: A Literature Review

Introduction: By 2050, the international prevalence of Alzheimer’s disease (AD) is expected to triple, resulting in immense healthcare costs and personal effect. In recent years, researchers have identified age-related hearing loss (ARHL) as one of the most prevalent causes in older adults to be associated with the predisposition for mild cognitive impairment (MCI) and AD. However, the relationship between the two remains unclear. Several plausible mechanisms explaining this hearing-cognition relationship have been suggested, such as social isolation, auditory activation, and neurobiological factors. This review seeks to investigate the literature examining the relationship between ARHL and dementia, how ARHL as a modifiable risk factor plays a role in the severity of cognitive decline in the AD and MCI population, and advocate for why further research on this topic is essential to help create a cognitively healthier and more informed older adult population. Methods: A comprehensive literature review of fifteen peer-reviewed articles was conducted using a predetermined protocol and inclusion criteria, such as keywords and databases. The search was limited to published articles in the English language from 2010 – present. Results: No associations were found between brain cortical thickness and those with AD and ARHL in comparison to those with SCD where an association was present. A moderate correlation was found between neurobiological factors such as ApoE4 to explain the relationship between AD and ARHL. The use of active hearing aids did not contribute to a cognitive benefit in those with moderate AD and ARHL compared to the use of placebo hearing aids, or after the secondary activation of hearing aids in the placebo group. Discussion: The literature shows inconclusive results about the mechanism linking ARHL and AD. The pattern of findings did not show consistent results between studies supporting a particular domain to explain the mechanism behind this relationship. Conclusion: Through conducting this review, a greater understanding and awareness about the role of ARHL as a risk factor of MCI and AD is provided. Ultimately, this is important in individual lifestyle changes to prevent the onset of ARHL, and subsequently dementia in order to live healthier and with higher quality as they age.

Association between Subclinical Epileptiform Discharge and the Severity of Cognitive Decline in Alzheimer's Disease: A Longitudinal Cohort Study.

Alzheimer's disease (AD) is the most common type of dementia. Aging is a risk factor for both AD and seizures. Subclinical epileptiform discharge (SED) has no evident clinical manifestation in patients with AD. Therefore, SED is liable to be overlooked in these patients since electroencephalography is not routinely performed in clinical settings. Previous studies about the association between SED and AD have yielded inconsistent results. The current study aimed to evaluate the prevalence of SED and its effect on AD severity and clinical outcomes. Patients with AD from Kaohsiung Municipal Ta-tung Hospital were included in this study. International 10-20 system scalp electroencephalography for 13 minutes was performed to detect SED. Clinical outcomes of patients with and without SED were assessed by neuropsychological tests [Cognitive Abilities Screening Instrument (CASI), Mini-Mental State Examination (MMSE), and Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB)]. 288 patients (mean age 80.5 years, 60.4% female) were enrolled in this study. Fifty-seven (19.8%) out of 288 patients with AD had SED. The prevalence of SED increased with the severity of cognitive impairment. Compared with patients without SED, those with SED showed significantly greater decline in CASI (-9.32 versus -3.52 points, p = 0.0001) and MMSE (-2.52 versus -1.12 points, p = 0.0042) scores in one year. SED may play a significant role in AD progression and is a potential therapeutic target.

Correlation of Global and Regional Amyloid Burden by 18 F-Florbetaben PET/CT With Cognitive Impairment Profile and Severity.

To assess the correlation between profile and severity deterioration in the neuropsychological assessment and the most affected regions in amyloid PET semiquantification. The influence of vascular risk and other potential confounding factors was also evaluated. A retrospective, observational, and multicenter study including all patients referred for amyloid PET in daily practice was conducted. Patients underwent neuropsychological assessment, and cognitive decline severity and domain(s) affected were recorded. The patients were grouped according to cognitive impairment (CI) profile and severity: (A) no CI, single-domain amnestic CI, multiple-domain amnestic CI, and nonamnestic CI; and (B) mild CI, moderate and severe dementia. An adapted Framingham Stroke Risk Profile was calculated for each individual. Depression and parkinsonism were also recorded. Standardized quantitative analysis software was used to obtain standardized uptake value ratio (SUVR) values from PET/CT images. The corresponding associations were assessed with the most appropriate statistical tests. One hundred twenty-nine patients were included (62 men, 67 women; 64.67 ± 7.47 years old). Significant differences in global and regional amyloid load were exclusively found in women between non-CI and moderate dementia ( P = 0.006, for total-cerebellum SUVR). Posterior and anterior cingulates and prefrontal cortex best represented CI severity ( P = 0.003, 0.006, and 0.006, respectively). No relationship between the CI profile and the regional amyloid load was shown. A significantly high positive correlation was found between age and vascular risk and between these variables and amyloid load in nearly all regions, especially in women with moderate dementia. Semiquantitative analysis of amyloid PET by SUVR values revealed a significant correlation between amyloid burden and CI severity, although only in women.

Distribution of Cortical Atrophy Associated with Cognitive Decline in Alzheimer's Disease: A Cross-Sectional Quantitative Structural MRI Study from PUMCH Dementia Cohort.

Quantitative measures of atrophy on structural MRI are sensitive to the neurodegeneration that occurs in AD, and the topographical pattern of atrophy could serve as a sensitive and specific biomarker. We aimed to examine the distribution of cortical atrophy associated with cognitive decline and disease stage based on quantitative structural MRI analysis in a Chinese cohort to inform clinical diagnosis and follow-up of AD patients. One hundred and eleven patients who were clinically diagnosed with probable AD were enrolled. All patients completed a systemic cognitive evaluation and domain-specific batteries. The severity of cognitive decline was defined by MMSE score: 1-10 severe, 11-20 moderate, and 21-30 mild. Cortical volume and thickness determined using 3D-T1 MRI data were analyzed using voxelbased morphometry and surface-based analysis supported by the DR. Brain Platform. The male:female ratio was 38:73. The average age was 70.8 ± 10.6 years. The mild: moderate: severe ratio was 48:38:25. Total grey matter volume was significantly related to cognition while the relationship between white matter volume and cognition did not reach statistical significance. The volume of the temporal-parietal-occipital cortex was most strongly associated with cognitive decline in group analysis, while the hippocampus and entorhinal area had a less significant association with cognitive decline. Volume of subcortical grey matter was also associated with cognition. Volume and thickness of temporoparietal cortexes were significantly correlated with the cognitive decline, with a left predominance observed. Cognitive deterioration was associated with cortical atrophy. Volume and thickness of the left temporal-parietal-occipital cortex were most important in early diagnosis and longitudinal evaluation of AD in clinical practice. Cognitively relevant cortices were left predominant.

Free Papers Compiled

INTRODUCTION:Preliminary studies suggestive of Acetyl-L-carnitine treatment have positive effects on patients depression with respects to fatigability and cognitive functions and also negative symptoms in patients diagnosed with schizophrenia.AIMThe aim of the study is to assess the effect of Acetyl-L carnitine as an add on therapy in patients with schizophrenia.OBJECTIVESTo assess the response of acetyl-L-carnitine as an augmented treatment in reduction of negative symptoms, cognitive decline severity in patients of schizophrenia.METHODOLOGY:Seventy five patients diagnosed with schizophrenia according to the DSM-5 criteria were selected for the study after meeting the inclusion criteria and written informed consent. Fifteen patients were dropped from the study due to multiple reasons, finally 60 patients completed the pre and post analysis. Two groups of the patients were taken randomly from Hospital, which were drug naïve psychotic patients. Both the groups were chosen according to inclusion and exclusion criteria as mentioned earlier. After analysis it was found that both the groups were comparable with respect to age, sex, education, occupation, marital status, family type and economic status ensuring more homogeneity among the groups as compared to previous studies (p value >0.05). After randomization, 30 patients were assigned for olanzepine group, and 30 for olanzepine + acetyl l carnitine group. All the patients were assessed with PANSS, MoCA, GAF at the baseline and follow up.Post analysis was done after 6 weeks of treatment. Baseline and follow up data was compared.RESULTS:Both group is very much significant in comparison with intra group. The two group medication is working fine. But the efficacy of ALC is unknown when comparing both groups.CONCLUSION:The results of the current study in conjunction with the results of other methodologically similar studies suggest that ALC can be used as an additional medication with the active ingredient olanzapine. There is no significant difference in effect of olanzapine mono-therapy vs. olanzapine augmented Acetyl-L-carnitine in patients with schizophrenia. Both group shows similar pattern in reduction of negative symptoms, cognitive decline severity in patients of schizophrenia.

548 - Cognitive aging and cognitive reserve

IntroductionThe aging processes are accelerating in all regions of the world. The involvement of older people in production and social processes determines the need to maintain a high level of social and psychological adaptation, despite the progressive pathology of the brain caused by its aging. This increases the relevance of research related to the study of biological reserves of the brain and psychological and social mechanisms of human adaptation in late adulthood. The risk of developing cognitive disorders is not fatal. According to some observations, even in the hippocampal type of UKR, despite the content of amyloid in the brain, the functional and social activity of the elderly remains high. Prospective studies show that people with high cognitive reserve have a lower risk of developing dementia. Cognitive reserve is the brain’s resistance to damage. Cognitive reserve is the ability of the brain to cope with the consequences of damage caused by external influences, brain stroke, chronic brain ischemia, neurodegenerative diseases, and age-related changes. Cognitive reserve is the brain’s ability to functionally compensate for and minimize clinical manifestations of cognitive impairment. The mechanisms of cognitive reserve in normal and Alzheimer’s disease are different. In healthy older adults, a higher cognitive reserve correlates with larger brain sizes and effective strategies for performing cognitive tasks. In the early stages of Alzheimer’s disease and Alzheimer’s disease, the size of the brain decreases. But high brain activity helps preserve cognitive resources. Excessive brain activity in dementia is a compensatory mechanism. This is confirmed by the results of functional magnetic resonance imaging of the brain. Of course, the degree of brain atrophy is a predisposing factor for dementia, but it is not a mandatory factor for cognitive decline. So, the symptoms of dementia do not appear until you have crossed the critical border of damage to the brain substance. Progressive brain atrophy underlies the clinical manifestations of dementia in neurodegenerative diseases, but the correlation between the degree of brain damage and cognitive impairment is not linear.Research materials and methodsAn observational 10-year longitudinal study was conducted. In 2006, moderate cognitive impairment was found in 66 patients. The group of patients included 49 women and 49 men. Their average age in 2006 was 59.3±5.2 years. In 2006, the severity of cognitive decline was 26.2±1.9 points on the MMSE scale. This corresponds to indicators of moderate cognitive impairment. Research methods: clinical and psychopathological, psychometric, statistical. Questionnaire “Loss and acquisition of personal resources” (N. Vodopyanova, M. Stein), MMSE scale.Research resultIn 2006, amyloid was detected in the spinal fluid of all patients selected for the study group. If a patient developed dementia, they were given specific therapy. The dynamics of cognitive functions in patients was different. Mild dementia was formed in 53% of patients. Moderate dementia was formed in 10.6% of patients. Moderate cognitive impairment (pre-dementia) persisted in 36.4% of patients. Hereditary burden of dementia in patients with moderate dementia was detected 2 times more often. Back in 2006, we identified the leading sensory systems of patients. The master sensor system determines the modality of the main information flow. This is the most important part of the information that a person interacts with. This is the basis of interaction with reality. This is the basis of cognitive functions. Correlations of age-specific lesions of the corresponding sensory systems with the severity of cognitive decline were found in patients with the corresponding sensory modality (Spearman’s Correlation Coefficient-r, p&lt;0.05): presbyacoussis – auditory r=0.667, presbyopia-visual r=0.705. The influence of psychosocial factors on the condition of patients was studied. In dementia, significant history of psychotrauma was found in 35.7%. Moderate stress was detected in the group of patients with moderate cognitive impairment in 33.3%. Moderate stress was detected in the group of patients with dementia in 83.3%. Stress of loss of life meaning was detected more often in patients with dementia 76.7%. It is important not only what stresses a person endures, but how they can cope with them. Dementia patients were statistically more likely to have unproductive coping strategies that did not help them cope adequately with stress.ConclusionsThe concept of cognitive reserve suggests possible causes of heterogeneity in the dynamics of cognitive decline in the initial stages of atrophic-degenerative brain diseases: biological causes and psychosocial causes. The concept of cognitive reserve helps to study and develop individual programs for the prevention of severe cognitive disorders.

Neuropsychiatric Symptoms in Mild Cognitive Impairment and Dementia Due to AD: Relation With Disease Stage and Cognitive Deficits.

Background: The interaction between neuropsychiatric symptoms, mild cognitive impairment (MCI), and dementia is complex and remains to be elucidated. An additive or multiplicative effect of neuropsychiatric symptoms such as apathy or depression on cognitive decline has been suggested. Unraveling these interactions may allow the development of better prevention and treatment strategies. In the absence of available treatments for neurodegeneration, a timely and adequate identification of neuropsychiatric symptom changes in cognitive decline is highly relevant and can help identify treatment targets.Methods: An existing memory clinic-based research database of 476 individuals with MCI and 978 individuals with dementia due to Alzheimer's disease (AD) was reanalyzed. Neuropsychiatric symptoms were assessed in a prospective fashion using a battery of neuropsychiatric assessment scales: Middelheim Frontality Score, Behavioral Pathology in Alzheimer's Disease Rating Scale (Behave-AD), Cohen-Mansfield Agitation Inventory, Cornell Scale for Depression in Dementia (CSDD), and Geriatric Depression Scale (30 items). We subtyped subjects suffering from dementia as mild, moderate, or severe according to their Mini-Mental State Examination (MMSE) score and compared neuropsychiatric scores across these groups. A group of 126 subjects suffering from AD with a significant cerebrovascular component was examined separately as well. We compared the prevalence, nature, and severity of neuropsychiatric symptoms between subgroups of patients with MCI and dementia due to AD in a cross-sectional analysis.Results: Affective and sleep-related symptoms are common in MCI and remain constant in prevalence and severity across dementia groups. Depressive symptoms as assessed by the CSDD further increase in severe dementia. Most other neuropsychiatric symptoms (such as agitation and activity disturbances) progress in parallel with severity of cognitive decline. There are no significant differences in neuropsychiatric symptoms when comparing “pure” AD to AD with a significant vascular component.Conclusion: Neuropsychiatric symptoms such as frontal lobe symptoms, psychosis, agitation, aggression, and activity disturbances increase as dementia progresses. Affective symptoms such as anxiety and depressive symptoms, however, are more frequent in MCI than mild dementia but otherwise remain stable throughout the cognitive spectrum, except for an increase in CSDD score in severe dementia. There is no difference in neuropsychiatric symptoms when comparing mixed dementia (defined here as AD + significant cerebrovascular disease) to pure AD.

Estimating premorbid intelligence in people living with dementia: a systematic review.

In diagnosing dementia, estimating premorbid functioning is critical for accurate detection of the presence and severity of cognitive decline. However, which assessments of premorbid intelligence are most suitable for use in clinical practice is not well established. Here, we systematically evaluate the validity of instruments for measuring premorbid intelligence in people living with dementia. In this systematic review, electronic databases (EMBASE, PsycINFO, MEDLINE, CINAHL, and AMED) were searched to identify studies reporting on objective measures of premorbid intelligence in dementia. Participants from included studies were recruited from local communities and clinical settings. A total of 1082 patients with dementia and 2587 healthy controls were included in the review. The literature search resulted in 13 eligible studies describing 19 different instruments. The majority of instruments (n = 14) consisted of language-based measures, with versions of the National Adult Reading Test (NART) being most commonly investigated. Preliminary evidence suggested comparable performance of patients with mild dementia and healthy controls on word reading tasks in English, Portuguese, Swedish, and Japanese. In moderate dementia, however, the performance was significantly impaired on most verbal tasks. There was a lack of reliability and validity testing of available instruments, with only one of the included studies reporting psychometric properties within the patient group. The results demonstrate that there is a wide range of tools available for estimating premorbid intelligence in dementia, with cautious support for the potential of word reading tasks across different languages in individuals with mild dementia. However, the review highlights the urgent need for extensive assessments of the psychometric properties of these tasks in dementia. We propose that further longitudinal research and assessments of nonverbal measures are necessary to validate these instruments and enhance diagnostic procedures for people living with dementia worldwide.

Influence of cardiovascular risk factors on pre-mild cognitive decline at middle and old age

Much attention is currently paid to non-dementia cognitive impairment, such as mild cognitive impairment and pre-mild cognitive decline (PMCD), since their timely detection and optimal correction increase the possibility of preventing dementia.Objective: to analyze the neuropsychological characteristics of patients with PMCD depending on the presence or absence of cardiovascular risk factors (CVRFs): hypertension, cardiac disorders (ischemic heart disease, intracardiac conduction disturbance), and prior stroke and myocardial infarction, as well as diabetes mellitus.Patients and methods. Examinations were made in 182 patients (132 women, 50 men; mean age, 59.32±5.41 years) with PMCD and CVFRs, 101 patients (77 women, 24 men; mean age, 59.45±7.04 years) with PMCD without CVRFs, and 77 control persons (55 women, 22 men; mean age, 60.55±5.65 years). All underwent general clinical, neurological, and clinical psychological studies using rating scales and tests.Results and discussion. The patients with PMCD and CVRFs had lower scores on all neuropsychological tests than the control group and on most tests than the patients with PMCD without CVRFs. In addition to some deterioration in memory indicators, the patients with CVRFs performed worse executive function tests. Cluster analysis showed that in the patients with PMCD, the severity of cognitive decline was considerably affected by hypertension, cardiac disorders, and diabetes mellitus; among them, hypertension was of the most significance.Conclusion. The association of cognitive decline with the burden of CVRFs indicates their important role in the deterioration of cognitive functions in PMCD.

Relationship between elevated impulsivity and cognitive declines in elderly community-dwelling individuals

Impulse control disorders are recognized as one of the behavioral and psychological symptoms of dementia (BPSD). Majority of studies on the treatment of BPSD related to impulsivity have rather focused on the aggression and agitation. In particular, it has not been investigated how cognitive declines are associated with impulsivity in community-dwelling elderly people. Here, we have measured the cognitive and memory functions and impulsivity of 212 elderly community-dwelling people using a psychometric test battery and analyzed the correlation between their level of impulsivity and cognitive functions by multiple regression analysis. We found an elevation of impulsivity, which was evaluated by the Barratt Impulsiveness Scale-11, closely related to decline of cognitive functions, which were evaluated by the Montreal Cognitive Assessment and the Mini-Mental State Examination, and Logical Memory function, which were evaluated by the Wechsler Memory Scale-Delayed Recall. Then we have divided them into groups based on the severity of cognitive decline and conducted an analysis of each group, the result of which showed that as this tendency was particularly noticeable in the suspected dementia group. Therefore, we have concluded that heightened impulsivity is negatively associated with cognitive and memory functions in community-dwelling elderly people.

Old Age Dementia: Clinical Patterns of Progression. Part 1

Background: the clinical experience testifies to the fact, that the increase of dementia severity in late age occurs quickly in some cases and in others it proceeds slowly, which is reflected in the total duration of the disease and survival. One of the aspects of dementias research is the study of significant differences in dementia progression rates.The objective of the review was to generalize the obtained data on progression rates of late age dementias of various genesis, first of all due to Alzheimer’s disease and its associated disorders.Material and methods: papers in MedLine/PubMed bases from1990 to 2020 were selected and analyzed according to the key words: “old age”, “dementia”, “Alzheimer’s disease”, “vascular dementia”, “progression”, “progression rate”, “disease trajectories”, as well as relevant papers in the references of the analyzed works.Conclusion: the history of research of old age dementias natural course was presented in the review of scientific publications. According to the results of development of progression rates detection methods, singling out of dementias with rapid and slow increase in the severity of cognitive decline was substantiated. Works devoted to the study of frequency and nosological belonging of dementias with different progression rates were considered. In the most recent studies prognostic models with detection of various trajectories of the course of the disease were developed. The concept of various dementias progression rates admittedly has practical meaning for provision of diagnostic and treatment assistance and planning of medical and social support measures for patients with dementia and their families. Differentiation of dementia progression clinical patterns during formation of comparable groups of patients seems appropriate for investigation of new therapy methods, as well as in clinical-biological studies of pathogenesis.