Dynamics of Cognitive Impairment in MCI Patients over a Three-Year Period: The Informative Role of Blood Biomarkers, Neuroimaging, and Genetic Factors.

Given the high growth rates of cognitive decline among the elderly population and the lack of effective etiological treatments, early diagnosis of cognitive impairment progression is an imperative task for modern science and medicine. It is of particular interest to identify predictors of an unfavorable subsequent course of cognitive disorders, specifically, rapid progression. Our study assessed the informative role of various risk factors on the dynamics of cognitive impairment among mild cognitive impairment (MCI) patients. The study included patients with MCI (N = 338) who underwent neuropsychological assessment, magnetic resonance imaging (MRI) examination, blood sampling for general and biochemical analysis, APOE genotyping, and polygenic risk score (PRS) evaluation. The APOE ε4/ε4 genotype was found to be associated with a diminished overall cognitive scores initial assessment and negative cognitive dynamics. No associations were found between cognitive changes and the PRS. The progression of cognitive impairment was associated with the width of the third ventricle and hematological parameters, specifically, hematocrit and erythrocyte levels. The absence of significant associations between the dynamics of cognitive decline and PRS over three years can be attributed to the provided suitable medical care for the prevention of cognitive impairment. Adding other risk factors and their inclusion in panels assessing the risk of progression of cognitive impairment should be considered.

Are subjective language complaints in memory clinic patients informative?

To diagnose mild cognitive impairment, it is crucial to understand whether subjective cognitive complaints reflect objective cognitive deficits. This question has mostly been investigated in the memory domain, with mixed results. Our study was one of the first to address it for language. Participants were 55-to-93-year-old memory clinic patients (n = 163). They filled in a questionnaire about subjective language and memory complaints and performed two language tasks (naming-by-definition and sentence comprehension). Greater language complaints were associated with two language measures, thus showing a moderate value in predicting language performance. Greater relative severity of language versus memory complaints was a better predictor, associated with three language performance measures. Surprisingly, greater memory complaints were associated with better naming, probably due to anosognosia in further disease progression or personality-related factors. Our findings highlight the importance of relative complaint severity across domains and, clinically, call for developing self-assessment questionnaires asking specific questions about multiple cognitive functions.

Alteration of Blood Immune Biomarkers in MCI Patients with Different APOE Genotypes after Cognitive Training: A 1 Year Follow-Up Cohort Study.

Many studies aim to detect the early phase of dementia. One of the major ways to achieve this is to identify corresponding biomarkers, particularly immune blood biomarkers. The objective of this study was to identify such biomarkers in patients with mild cognitive impairment (MCI) in an experiment that included cognitive training. A group of patients with MCI diagnoses over the age of 65 participated in the study (n = 136). Measurements of cognitive functions (using the Mini-Mental State Examination scale and Montreal Cognitive Assessment) and determination of 27 serum biomarkers were performed twice: on the first visit and on the second visit, one year after the cognitive training. APOE genotypes were also determined. Concentrations of EGF (F = 17; p = 0.00007), Eotaxin (F = 7.17; p = 0.008), GRO (F = 13.42; p = 0.0004), IL-8 (F = 8.16; p = 0.005), MCP-1 (F = 13.46; p = 0.0001) and MDC (F = 5.93; p = 0.016) increased after the cognitive training in MCI patients. All these parameters except IL-8 demonstrated a weak correlation with other immune parameters and were poorly represented in the principal component analysis. Differences in concentrations of IP-10, FGF-2, TGFa and VEGF in patients with MCI were associated with APOE genotype. Therefore, the study identified several immune blood biomarkers that could potentially be associated with changes in cognitive function.

Inflammatory biomarkers and lipid metabolism parameters in women with mild cognitive impairment and dementia.

The detection of specific markers of dementia and mild cognitive decline (MCI) could be the key to disease prevention and forehanded treatment. Female gender is one of the major risk factor for dementia. The aim of our study was to compare serum concentration of some factors related to lipid metabolism and the immune system in patients with MCI and dementia. The study was performed on women >65 years old: controls (n = 75), diagnosed with dementia (n = 73) and MCI (n = 142). Patients were evaluated using Mini-Mental State Examination, Clock Drawing Test and Montreal Cognitive Assessment scales in the period 2020-2021. The level of Apo A1 and HDL was significantly decreased in patients with dementia; the level of Apo A1 was also decreased in MCI. EGF, eotaxin-1, GRO-α, and IP-10 were elevated in patients with dementia compared to the controls. IL-8, MIP-1ß, sCD40L, and TNF-α levels were decreased in MCI patients and increased in patients with dementia compared to the control. Serum VEGF levels were decreased in MCI and dementia patients in comparison with the control. We hypothesize that no single marker can indicate a neurodegenerative process. Future research should focus on identifying markers to determine possible diagnostic combinations that can reliably predict neurodegeneration.

Suicide-Related Single Nucleotide Polymorphisms, rs4918918 and rs10903034: Association with Dementia in Older Adults.

Dementia has enormous implications for patients and the health care system. Genetic markers are promising for detecting the risk of cognitive impairment. We hypothesized that genetic variants associated with suicide risk might significantly increase the risk of cognitive decline because suicide in older adults is often a consequence of cognitive impairment. We investigated several single-nucleotide polymorphisms that were initially associated with suicide risk in dementia older adults and identified the APOE gene alleles. The study was performed with subjects over the age of 65: 112 patients with dementia and 146 healthy volunteers. The MMSE score was used to assess cognitive functions. Study participants were genotyped using real-time PCR (APOE: rs429358, rs7412; genes associated with suicide: rs9475195, rs7982251, rs2834789, rs358592, rs4918918, rs3781878, rs10903034, rs165774, rs16841143, rs11833579 rs10898553, rs7296262, rs3806263, and rs2462021). Genotype analysis revealed the significance of APOEε4, APOEε2, and rs4918918 (SORBS1) when comparing dementia and healthy control groups. The association of APOEε4, APOEε2, and rs10903034 (IFNLR1) with the overall MMSE score was indicated. The study found an association with dementia of rs4918918 (SORBS1) and rs10903034 (IFNLR1) previously associated with suicide and confirmed the association of APOEε4 and APOEε2 with dementia.

Positive Effect of Cognitive Training in Older Adults with Different APOE Genotypes and COVID-19 History: A 1-Year Follow-Up Cohort Study.

(1) Background: Older people suffer from cognitive decline; several risk factors contribute to greater cognitive decline. We used acquired (COVID-19 infection) and non-modifiable (presence of APOE rs429358 and rs7412 polymorphisms) factors to study the progression of subjective cognitive impairment while observing patients for one year. Cognitive training was used as a protective factor. (2) Methods: Two groups of subjects over the age of 65 participated in the study: group with subjective cognitive decline receiving cognitive training and individuals who did not complain of cognitive decline without receiving cognitive training (comparison group). On the first visit, the concentration of antibodies to COVID-19 and APOE genotype was measured. At the first and last point (1 year later) the Mini-Mental State Examination scale and the Hospital Anxiety and Depression Scale were performed. (3) Results: COVID-19 infection did not affect cognitive function. A significant role of cognitive training in improving cognitive functions was revealed. Older adults with APOE-ε4 genotype showed no positive effect of cognitive training. (4) Conclusions: Future research should focus on cognitive dysfunction after COVID-19 in long-term follow-up. Attention to the factors discussed in our article, but not limited to them, are useful for a personalized approach to maintaining the cognitive health of older adults.

A Comparison of Regional Brain Volumes in Older Adults With and Without History of COVID-19: Региональные объемы мозга у Ð¿Ð¾Ð¶Ð¸Ð»Ñ‹Ñ Ð»ÑŽÐ´ÐµÐ¹ с наличием и отсутствием COVID-19 в анамнезе.

BACKGROUND: Recent studies have shown that SARS-CoV-2 can have neuropsychiatric consequences and has the ability to penetrate the blood-brain barrier. If SARS-CoV-2 has a specific route of entry into the brain, it may leave imprints in the form of specific changes in brain morphology. Older individuals are most vulnerable to the neuropsychiatric COVID-19 complications. This study aims to compare regional brain volumes in older adults individuals with and without COVID-19 history (COVID+ and COVID-, respectively). METHODS: Individuals over 65 years old who applied for treatment to the Memory Clinic (Mental-Health Clinic No. 1 named after N.A. Alexeev, Moscow, Russia) were assessed between October 2020 and April 2021. Their COVID-19 history was determined by the self-report and COVID-19 certificate. Individuals with severe neuropsychiatric or acute or severe chronic somatic or infectious disease and those taking medications potentially affecting cognitive functioning were excluded. All participants underwent MRI examinations followed by image segmentation and morphometric quantitative analysis. Regional brain volumes were compared in COVID+ and COVID- people. RESULTS: 207 participants were included in the study. The COVID+ group consisted of 24 participants. The comparison between groups revealed statistically significant differences in left amygdala area (median 1199.3 mm3 in COVID+ vs. 1263.7 mm3 in COVID-) and right postcentral gyrus volumes (median 8055.5 mm3 in COVID+ vs. 8434.0 mm3 in COVID-). Then case-control analysis was performed in individuals matched for gender, age and common somatic causes of structural brain changes (hypertension and/or diabetes mellitus type 2) for 22 subjects in each group. Statistically significant differences in regional brain volumes between groups were absent. CONCLUSION: We did not find strong evidence for any regional brain volumes changes in people older than 65 years with a history of COVID-19 in comparison to those without history of COVID-19. Though, given study limitations, these results cannot be generalized to other people who recovered from COVID-19.