Progression Of Cognitive Disorders Research Articles

Spotlight on pro-inflammatory chemokines: regulators of cellular communication in cognitive impairment.

Cognitive impairment is a decline in people's ability to think, learn, and remember, and so forth. Cognitive impairment is a global health challenge that affects the quality of life of thousands of people. The condition covers a wide range from mild cognitive impairment to severe dementia, which includes Alzheimer's disease (AD) and Parkinson's disease (PD), among others. While the etiology of cognitive impairment is diverse, the role of chemokines is increasingly evident, especially in the presence of chronic inflammation and neuroinflammation. Although inflammatory chemokines have been linked to cognitive impairment, cognitive impairment is usually multifactorial. Researchers are exploring the role of chemokines and other inflammatory mediators in cognitive dysfunction and trying to develop therapeutic strategies to mitigate their effects. The pathogenesis of cognitive disorders is very complex, their underlying causative mechanisms have not been clarified, and their treatment is always one of the challenges in the field of medicine. Therefore, exploring its pathogenesis and treatment has important socioeconomic value. Chemokines are a growing family of structurally and functionally related small (8-10 kDa) proteins, and there is growing evidence that pro-inflammatory chemokines are associated with many neurobiological processes that may be relevant to neurological disorders beyond their classical chemotactic function and play a crucial role in the pathogenesis and progression of cognitive disorders. In this paper, we review the roles and regulatory mechanisms of pro-inflammatory chemokines (CCL2, CCL3, CCL4, CCL5, CCL11, CCL20, and CXCL8) in cognitive impairment. We also discuss the intrinsic relationship between the two, hoping to provide some valuable references for the treatment of cognitive impairment.

Design of the Dutch multicentre study on opportunistic screening of geriatric patients for atrial fibrillation using asmartphone PPG app: the Dutch-GERAF study.

Screening of high-risk patients is advocated to achieve early detection and treatment of clinical atrial fibrillation (AF). The Dutch-GERAF study will address two major issues. Firstly, the effectiveness and feasibility of an opportunistic screening strategy for clinical AF will be assessed in frail older patients and, secondly, observational data will be gathered regarding the efficacy and safety of oral anticoagulation (OAC). This is amulticentre study on opportunistic screening of geriatric patients for clinical AF using asmartphone photoplethysmography (PPG) application. Inclusion criteria are age ≥ 65years and the ability to perform at least three PPG recordings within 6months. Exclusion criteria are the presence of acardiac implantable device, advanced dementia or asevere tremor. The PPG application records patients' pulse at their fingertip and determines the likelihood of clinical AF. If clinical AF is suspected after apositive PPG recording, aconfirmatory electrocardiogram is performed. Patients undergo acomprehensive geriatric assessment and afrailty index is calculated. Risk scores for major bleeding (MB) are applied. Standard laboratory testing and additional laboratory analyses are performed to determine the ABC-bleeding risk score. Follow-up data will be collected at 6months, 12months and 3years on the incidence of AF, MB, hospitalisation, stroke, progression of cognitive disorders and mortality. The Dutch-GERAF study will focus on frail older patients, who are underrepresented in randomised clinical trials. It will provide insight into the effectiveness of screening for clinical AF and the efficacy and safety of OAC in this high-risk population. NCT05337202.

Assessment of cognitive functions in patients with arterial hypotension

Objective. To conduct a study of cognitive functions in young people (1844 years old) with arterial hypotension, to determine the prognostic significance of arterial hypotension in the development of cognitive impairment.
 Materials and methods. A survey in patients aged 1844 years with arterial hypotension was conducted in electronic format using the Google Forms service (Google Forms). The survey involved 100 persons with arterial hypotension, the control group consisted of 50 persons. Data processing was carried out using Microsoft Excel as well as statistical methods were used.
 Results. Arterial hypotension is the result of a functional disorder of the nervous system and it leads to some unpleasant symptoms: loss of strength, weakness, lethargy, decreased concentration, memory impairment and many other signs that can reduce the quality of life of people. In general, arterial hypotension does not lead to significant impairment of cognitive functions at a young age, but in such patients, attention, concentration, working memory and speech function get worse to some extent.
 Conclusions. Arterial hypotension can be a risk factor for the onset and progression of cognitive disorders, therefore, in all patients with this disease, close attention should be paid to the state of higher mental functions while conducting such simple clinical and psychological studies using cognitive function assessment scales to track dynamics.

Abstract MP15: Arterial Hypertension And Cognitive Disorders: Cerebral Vascular Reserve

The study of functional and restructuring disorders of large and small cerebral vessels that are a target for arterial hypertension (AH) is important for the prognosis of cognitive disorders (CD). The relationship between cerebral vascular reserve and CD in 378 outpatients with controlled AH stage II and low SCORE risk of CVD examined. The median age – 57,3±8,91 years. The average duration of AH was 11,5±6,2 years. SCORE risk of CVD <5 %. All AH patients were examined according to the international recommendations and cognitive functioning was assessed by MoCA scale, blood flow in the middle cerebral artery was investigated by transcranial Doppler (TCD) on the HDI 7, Philips, USA with functional respiratory hypo- and hypercapnic ventilation tests.The integrative index of vasomotor reactivity (IVMR) was calculated for cerebral vascular reserve identification: IVMR=[(V apnea -V hyper )/V 0 ]•100%, V apnea - the average maximum velocity of blood flow after 20s of apnea (cm/s), V hyper - the average maximum velocity of blood flow after 20s of hyperventilation (cm/s), V 0 - the average maximum velocity at rest (cm/s). Non-dementia cognitive disorders were found in 125 (33 %) - 24,32±0,11 points on MOCA scale. The significant decrease in the IVMR was found according to the results of the TCD examination of cerebralvascular reserve testing in patients with AH and CD (44.0±1.2, p<0,001), which indicates the close relationship between the value of IVMR and CD even in patients with controlled AH (rs = +0.54; p<0.001). It is necessary to clarify the cerebral vascular reserve and the vasomotor reactivity index even when controlling AH due to the high risk of the development and progression of cognitive disorders, which worsen the prognosis of cardiovascular events and quality of life.

Cognitive Impairment and Treatment Compliance in Patients with Chronic Heart Failure

Objectives. To identify the risk factors for the development of cognitive impairments and the low treatment compliance seen in patients with chronic heart failure (CHF). Materials and methods. A total of 157 patients with CHF and 32 control subjects took part in the study. Neuropsychological investigations were carried out using a 30-min set of tests recommended by the NINDS-Canadian Stroke Standards – echocardioscopy, brain MRI scans, and cognitive event-related potentials (ERP) – along with assessment of treatment compliance. Results and conclusions. Treatment regime violations were seen in 62% of cases. Decreases in compliance were associated with increases in the severity of subcortical (frontal lobes) and periventricular leukoaraiosis, slowing of decision-taking processes (increases in the latency of the ERP P300 peak), and degradation of test performance for assessment of speech activity, optical-spatial, frontal-dysregulatory functions, and memory. Among patients with low treatment compliance, 58% showed frontal-dysregulatory cognitive disorders, 21% combined disorders, and 40% amnestic disorders. Risk factors for progression of cognitive disorders and low treatment compliance were a reduced fractional output and the restrictive type of diastolic cardiac dysfunction.

Pathophysiologic aspects of the development of cognitive disorders in chronic heart failure in elderly patients

The present literature review presents current views on pathophysiologic aspects of the formation and progression of cognitive disorders in chronic heart failure in elderly patients. Advanced age itself is an important predictor of the development of cardiovascular, neurodegenerative and other diseases. Involutive changes of cardiovascular system are known to potentiate the development of chronic heart failure. Heart failure in older people usually develops gradually. Formation of the cognitive deficit in heart disease is associated with chronic cerebral ischemia as well as a cascade of neurochemical processes occurring in the brain, eventually forming a vicious circle. Often the symptoms of cerebral ischemia due to reduced stroke volume occur much earlier than congestion signs in other organs and systems. Chronic cerebral ischemia that occurs due to violation of cerebral hemodynamics, is associated with both extracerebral and intracerebral causes, which in turn contributes to the development of chronic brain hypoxia and aggravation of cognitive dysfunction. Thus, the features of the development and course of disease in people of older age groups indicate that in geriatric practice existing diagnostic schemes are not always applicable. When observing patients of elderly and senile age with chronic heart failure, during the assessment of their condition and running diagnostic tests, special attention should be payed to the earliest detection of cognitive dysfunction signs in order to correct the patient's treatment and improve quality of life.

PP.29.15] COGNITIVE FUNCTION AND OVERWEIGHT IN PATIENTS WITH HYPERTENSION

Objective: Epidemiological studies present compelling evidence that hypertension is a significant risk factor for the development and progression of cognitive disorders (CD), and obesity accelerates the development of CD on the base of metabolic disorders. Design and method: 274 patients with controlled hypertension were examined. The average age was 53,8 ± 5,7 years. The average duration of hypertension was 10,5 ± 4,9 years. Body mass index (BMI) was increased in 62.8%. All patients with higher and secondary education were employed. The average systolic blood pressure was within 137,9 ± 1,82 mmHg, average diastolic blood pressure - 80,3 ± 3,06. Overweight and obesity were recorded in 65 patients (20.4%). Standard examinations, BMI and additional diagnostic procedureswere performed: ambulatory blood pressure monitoring, ultrasound of the main arteries of the head and neck and neuropsychological profile of cognitive functions by MMSE scale, Luria memory test - Remembering the 10 words, attention and speed of sensorimotor reactions - by Schulte and Rybakov. Results: Only 12% of patients in the total group complained of storing information problems. CD were revealed in 93 patients - 33.9%, and among those with overweight and obesity, CD was registered in 58 - 89%. Thickening of intima-media was identified only in 48 patients, primarily in patients with obesity (58.3%). Light CD were in 37.6%, moderate in - 55.5% and mild dementia only in 6.9%. The most significant were violations of attention and speed of sensorimotor reactions that affect a relevant role-scale functioning of life quality (SF-36 HSS). Conclusions: Every third patient, even with controlled hypertension, and two thirds of those with overweight and obesity present mild to moderate CD, that indicates early brain damage as the target organ.

Montreal Cognitive Assessment and Mini-Mental State Examination reliable change indices in healthy older adults.

Cognitive tests are used repeatedly to assess the treatment response or progression of cognitive disorders. The Montreal Cognitive Assessment (MoCA) is a valid screening test for mild cognitive impairment. The aim of our study was to establish 90% reliable change indices (RCI) for the MoCA together with the Mini-Mental State Examination (MMSE) in cognitively healthy older adults. We analyzed 197 cognitively healthy and functional independent volunteers aged 60-94 years, who met strict inclusion criteria for four consecutive years. The RCI methods by Chelune and Hsu were used. For 1, 2, and 3 years, the 90% RCI for MoCA using Chelune's formula were -4 ≤, ≥4; -4 ≤, ≥4 and -5 ≤, ≥4 points, respectively, and -3 ≤, ≥3 for the MMSE each year. Ninety percent RCI for MoCA using Hsu's formula ranged from -6 to 0, respectively, and +3 to +8 dependent on the baseline MoCA. Our study demonstrated RCI for the MoCA and MMSE in a 3-year time period that can be used for the estimation of cognitive decline or improvement in clinical settings. Copyright © 2016 John Wiley & Sons, Ltd.

Cognitive disorders in Parkinson's disease: Confirmation of a spectrum of severity.

Clinical presentation and progression of cognitive disorders in Parkinson's disease (PD) is heterogeneous. Our objective was to confirm prospectively a previous exploratory cluster analysis based on retrospective data that identified five cognitive phenotypes in PD. A model-based confirmatory cluster analysis was conducted on the results of neuropsychological tests administered in 156 PD patients from two European movement disorder centers (Lille, n=81; Maastricht, n=75). The number of clusters was determined on the basis of statistical criteria as well as clinical plausibility. A factorial discriminant analysis assessed the quality of the clusters' separation. A five-cluster model was statistically superior and clinically the most relevant. These clusters can be described as follows: 1) cognitively intact patients with high level of performance in all cognitive domains (25.64%), 2) cognitively intact patients slightly slower than those in cluster 1 (26.92%), 3) patients with deficits in executive functions (37.18%), 4) patients with severe deficits in all cognitive domains, particularly executive functions (3.20%), 5) patients with severe deficits in all cognitive domains, particularly working memory and recall in verbal episodic memory (7.05%). The groups differed in terms of age, apathy and frequency of hallucinations that were all higher in the clusters with cognitive deficits, and the duration of formal education was lower in those groups. We confirm our previous exploratory analysis. Cognitive disorders in PD patients are heterogeneous and can be separated in five clusters ranging from patients with performance in the normal range to patients with severe disorders in all cognitive domains.

Clinical and laboratory correlation in patients with consequences of traumatic brain injury

The aim of this study was to establish main peculiarities of apoptosis of peripheral blood leukocytes in patients with traumatic brain injury consequences of varying severity under conditions of disease progression Methods . In 220 patients with the effects of light (71), moderate (59) and hard (90) TBI and the catamnesis of trauma in the age from 1 to 30 years percentage of peripheral blood leukocytes in stage of apoptosis (ANV +) and necrotic (PI +) and the level of reactive oxygen species (ROS +) was explored by flow cytofluorometry method. The control group consisted of 30 people representative by age and sex. Neurological status was assessed by Neurological Outcome Scale for Traumatic Brain Injury (NOS-TBI), cognitive status - Montreal scale for cognitive deficit (Mosa), the level of anxiety and depression – by the HADS scale Results. Patients with TBI consequences of varying severity established significant growth indicators characterizing the level of necrosis and apoptosis of peripheral blood leukocytes, and increase the percentage of cells containing active oxygen species. Reliable dependence of indicators RI + ANV + peripheral blood leukocytes and ROS + on patient's age, duration and type of injury was not found Conclusions. Conditioned upon progression of neurological deficit (accession of extra-pyramidal symptoms, occurrence and progression of cognitive disorders, etc.) significantly higher values RI + ANV + peripheral blood leukocytes and ROS + were found

Polymorphism of genes associated with increased cardiovascular risk and cognitive function in patients with chronic heart failure and in healthy persons: the pilot study

There was studied the relationship between polymorphic variants of APOC3 (rs2854117), PON1 (rs854560, rs662), AGT (rs4762, rs699) and AGTR1 (rs5186) genes with the results of cognitive tests in patients with chronic heart failure (СHF) of ischemic genesis and healthy persons. The general group included 50 patients with CHF of II-IV functional classes, the control group - 50 healthy volunteers. Cognitive functions were estimated by 5th and 7th subtests of Wexler and Burdon's test. There was revealed statistically significant correlation between the polymorphism of APOC3, PON1, AGT, AGTR1 genes and the results of cognitive tests in patients with CHF and healthy persons. These data suggest that the polymorphism of the studied genes may be important in the genetic susceptibility to the formation and progression of cognitive disorders.

INTERRELATION OF ATHEROSCLEROSIS RISK FACTORS AND CENTRAL NERVOUS SYSTEM CONDITION IN PATIENTS WITH CHRONIC HEART FAILURE OF ISCHEMIC ORIGIN

Aim. Chronic heart failure is one of the factors of the development and progression of cognitive disorders. To study the relationships between risk factors of atherosclerosis and condition of the central nervous system in patients with chronic heart failure of ischemic etiology. Material and methods. Cognitive tests, echocardiography, ultrasound investigation of carotid arteries, MRI of the brain and measurement of homocystein, CRP, lipid profile in venous blood were performed in 57 patients with I–IV functional class of chronic heart failure. Program STATISTICA7 (methods of incremental regression analysis) were used to assess the results. Results. Strong interactions between worsening of cognitive functions and increase of homocystein level, increase of thickness of IMC, decrease of low-density lipoprotein cholesterol were revealed. Decrease of thickness of the cerebral grey matter and increase of apparent diffusion coefficient of water molecules of the brain were associated with increased C-reactive protein levels, cholesterol of low density lipoproteins and high-density lipoproteins and with decrease of the thickness of carotid IMC. The decrease of thickness of middle legs of cerebellum was associated with reduced levels of low-density and high-density lipoprotein cholesterol. Conclusion. The relationship between risk factors of atherosclerosis, cognitive functions, and morphological changes of the brain was revealed.

Cardiac Index as a Correlate of Brain Volume

The importance of vascular risk factors in the development and progression of cognitive disorders is gaining appreciation; the term “vascular cognitive disorders” refers to the common situation in which vascular damage plays a role, either alone or in combination with a neurodegenerative or other process, in the development of cognitive impairment or dementia. Numerous vascular risk factors have been implicated in vascular cognitive disorders, and many of these have been linked to cognitive decline through white matter damage and brain atrophy.1–8 As the American Heart Association launches its new strategic plan to improve the cardiovascular health of all Americans by 20%, a greater focus on ideal cardiovascular health will likely lead to improved brain health and therefore cognitive health. To address the health needs of our aging population, a better understanding of the links between cardiovascular disease and brain structure and function will be required. In addition, it will be important to identify early markers of unsuccessful aging to test interventions that can improve outcomes. Article see p 690 Various quantitative measures are now available to help us understand the relationships between vascular disease and brain health. These include neuropsychological testing, structural and functional magnetic resonance imaging, and metabolic imaging with magnetic resonance imaging and positron emission tomography. These tools have helped us better quantify changes in brain structure and metabolism and relate them to associations between aging, neurovascular risk factors, and cognitive function. In this issue of Circulation , Jefferson et al9 report an association between cardiac index and brain volume and relate these to cognitive function in a subsample of the well-characterized Framingham Study (participants were healthier than the overall cohort, being well enough to undergo magnetic resonance imaging). The brain volumes of participants were smaller among those with lower cardiac index values, even after adjustment …

Stress and dementia: the role of the hypothalamic-pituitary-adrenal axis

Hippocampus plays a crucial role in learning and memory and, in spite of its remarkable plasticity, it is also particularly sensitive to stress hormones due to its high concentration of corticosteroid receptors. Indeed, adrenal steroids modulate hippocampal plasticity, acting on excitability and long term potentiation or depression. By a chronobiological approach, we studied the cortisol and DHEAS secretion in clinically healthy old subjects and in age-matched demented patients, including both the degenerative and the vascular type. When compared to young controls, both clinically healthy elderly subjects and demented patients, particularly those with AD, had significantly higher cortisol levels at night time, i.e. at the moment of the maximal sensitivity of HPA axis to stimulatory or inhibitory inputs. At the same time, a clear age- and disease-dependent reduction of DHEAS secretion was found. Thus the cortisol to DHEAS molar ratio was significantly higher in healthy old subjects, and even more in demented patients, when compared to young controls, and significantly linked to both age and cognitive impairment. Finally, the quantitative and qualitative changes of the adrenal secretory pattern were significantly correlated with the decline of hippocampal volumes, measured by MRI. In conclusion, several lines of evidence deal with a pathogenetic role of stress hormones in the occurrence and progression of cognitive disorders in elderly subjects. The consequent hippocampal neuronal impairment may in turn be responsible for the continuous activation of HPA axis and the increased hypothalamic expression of vasopressin and corticotropin releasing hormone.

Homocysteine and dementia

Homocysteine is a vascular risk factor including cerebral macroangiopathy and microangiopathy. Furthermore, there might also be an association with cognitive disorders including vascular dementia and Alzheimer's disease. Hyperhomocysteinemia linked with cognitive impairment might be an indirect marker for low concentrations of vitamin B 12, vitamin B 6 or folate, resulting from low intake or from an impaired transport of the vitamins to the brain. Another possibility is a direct harmful effect of homocysteine to cognition via vascular and neurotoxic pathophysiologic mechanisms. Because hyperhomocysteinemia is a potentially reversible risk factor and can be identified early, it should be investigated by prospective intervention studies whether lowering homocysteine levels by vitamin supplementation could reduce incidence and progression of cognitive disorders.