Mild Cognitive Decline Research Articles

Clinical, neuroimaging and genetic findings in the Japanese case series of CLCN2-related leukoencephalopathy.

Clinical, neuroimaging and genetic findings in the Japanese case series of CLCN2-related leukoencephalopathy.

Quantification of baseline amyloid PET in individuals with subjective cognitive decline can identify risk of amyloid accumulation and cognitive worsening: the FACEHBI study.

Amyloid PET imaging is capable of measuring brain amyloid load in vivo. The aim of this study is to assess the relationship of the baseline amyloid with its accumulation over time and with cognition in individuals with subjective cognitive decline (SCD), giving a focus on those below Aβ positivity thresholds. 118 of 197 individuals with SCD from the Fundació ACE Healthy Brain Initiative underwent three [18F]florbetaben scans and the remaining 79 underwent two scans in a 5-year span. Individuals were categorised based on baseline Centiloid values (CL) into amyloid positive (Aβ+; CL > 35.7), Grey Zone (GZ; 20 < CL ≤ 35.7), and amyloid negative (Aβ-; CL ≤ 20). Relationship between conversion to mild cognitive decline (MCI) and baseline amyloid levels was assessed. Then, to focus on sub-threshold individuals with amyloid accumulation, the Aβ- group was split into two groups (N1 (CL ≤ 13.5) and N2 (13.5 < CL ≤ 20)), Aβ accumulation was determined, and a parametric image analysis of the Aβ accumulators in the N1 group was performed. At baseline, 20 individuals were Aβ+, 8 GZ, 160 N1, and 9 N2. Higher Aβ load, older and less educated individuals presented increased risk of MCI-conversion. Longitudinally, 19% of N1 individuals were accumulators despite very low Aβ burden at baseline. Meanwhile, 89% of the N2 group accumulated Aβ as well as all GZ individuals (which had the highest rate of amyloid accumulation, 5.1 CL/year). In the parametric image analysis of N1 accumulators, a region within the precuneus was linked to increased Aβ over time. Baseline amyloid levels differentiate individuals who accumulate amyloid over time and that are at risk for cognitive decline, including those at sub-threshold levels of Aβ. This can be valuable to identify pre-clinical AD in a SCD population.

Proof-of-Concept Study on the Use of Virtual Reality with Evocative and Aesthetic Content for Elderly Individuals with Cognitive Decline

Recent technological advances have introduced novel therapeutic interventions for Alzheimer’s disease (AD). This study introduces a novel virtual reality (VR) intervention consisting of aesthetically pleasing and relaxing immersive videos paired with evocative music for patients with or without cognitive decline. The goal of this intervention is to improve the mood, evoke autobiographical memories in, and enhance the overall well-being of elderly individuals, across stages of cognitive decline (from absent to severe). Twenty-one elderly participants (5 cognitively healthy, 13 with a mild cognitive decline, 2 with a moderate decline, and 1 with a severe decline) were exposed to immersive 360-degree videos depicting both familiar and unfamiliar, pleasant and calming environments, accompanied by emotionally evocative, pleasant, and soothing music. The results demonstrated high levels of immersion and predominantly positive emotional responses, with several participants reporting autobiographical memory recall triggered by the VR stimulation. Statistical analysis revealed a significant improvement in mood over time, regardless of cognitive status, supporting the effectiveness of the intervention. While there were some side effects of fatigue or transient anxiety, the experience was generally perceived as engaging and meaningful. This feasibility study adds to the acceptability and potential clinical utility of VR interventions and provides a justification for future larger trials aimed at the integration of immersive technologies into cognitive rehabilitation interventions for individuals at different stages of cognitive decline.

Bilateral Middle Cerebellar Peduncle Sign in a Patient with Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy and Coronavirus Disease 2019.

A 59-year-old man without risk factors for atherosclerosis was diagnosed with coronavirus disease 2019 (COVID-19). Four days later, he developed dysarthria and gait disturbance. Neurological examination revealed slurred speech, ataxia, and mild cognitive decline. Brain magnetic resonance imaging revealed multiple infarcts in the bilateral middle cerebellar peduncles and leukoencephalopathy, indicating the diagnosis of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Genetic testing confirmed a pathogenic NOTCH3 variant (c.505C>T, p.Arg169Cys) (NM_000435.3). A skin biopsy supported the diagnosis. He was treated with cilostazol and after three months of rehabilitation, he regained an independent walking ability. COVID-19 increases the risk of ischemic stroke in CADASIL patients, with bilateral middle cerebellar peduncle infarctions being notable in the present case.

The Cognitive Interplay: Exploring the Relationship Between Mild Behavioral Impairment, Cognitive Decline and Cognitive Reserve (P2-3.008)

The Cognitive Interplay: Exploring the Relationship Between Mild Behavioral Impairment, Cognitive Decline and Cognitive Reserve (P2-3.008)

Gene therapy rescues brain edema and motor function in a mouse model of megalencephalic leukoencephalopathy with subcortical cysts.

Gene therapy rescues brain edema and motor function in a mouse model of megalencephalic leukoencephalopathy with subcortical cysts.

Cognitive Decline and Food Insecurity in Older Brazilian Adults Registered with Primary Health Care: A Cross-sectional Study

Cognitive Decline and Food Insecurity in Older Brazilian Adults Registered with Primary Health Care: A Cross-sectional Study

Reduction of Neuroinflammation as a Common Mechanism of Action of Anorexigenic and Orexigenic Peptide Analogues in the Triple Transgenic Mouse Model of Alzheimer´s Disease

Alzheimer’s disease (AD) is the most common form of dementia. Characterized by progressive neurodegeneration, AD typically begins with mild cognitive decline escalating to severe impairment in communication and responsiveness. It primarily affects cerebral regions responsible for cognition, memory, and language processing, significantly impeding the functional independence of patients. With nearly 50 million dementia cases worldwide, a number expected to triple by 2050, the need for effective treatments is more urgent than ever. Recent insights into the association between obesity, type 2 diabetes mellitus, and neurodegenerative disorders have led to the development of promising treatments involving antidiabetic and anti-obesity agents. One such novel promising candidate for addressing AD pathology is a lipidized analogue of anorexigenic peptide called prolactin-releasing peptide (palm11-PrRP31). Interestingly, anorexigenic and orexigenic peptides have opposite effects on food intake regulation, however, both types exhibit neuroprotective properties. Recent studies have also identified ghrelin, an orexigenic peptide, as a potential neuroprotective agent. Hence, we employed both anorexigenic and orexigenic compounds to investigate the common mechanisms underpinning their neuroprotective effects in a triple transgenic mouse model of AD (3xTg-AD mouse model) combining amyloid-beta (Aβ) pathology and Tau pathology, two hallmarks of AD. We treated 3xTg-AD mice for 4 months with two stable lipidized anorexigenic peptide analogues – palm11-PrRP31, and liraglutide, a glucagon-like peptide 1 (GLP-1) analogue – as well as Dpr3-ghrelin, a stable analogue of the orexigenic peptide ghrelin, and using the method of immunohistochemistry and western blot demonstrate the effects of these compounds on the development of AD-like pathology in the brain. Palm11-PrRP31, Dpr3-ghrelin, and liraglutide reduced intraneuronal deposits of Aβ plaque load in the hippocampi and amygdalae of 3xTg-AD mice. Palm11-PrRP31 and Dpr3-ghrelin reduced microgliosis in the hippocampi, amygdalae, and cortices of 3xTg-AD mice. Palm11-PrRP31 and liraglutide reduced astrocytosis in the amygdalae of 3xTg-AD mice. We propose that these peptides are involved in reducing inflammation, a common mechanism underlying their therapeutic effects. This is the first study to demonstrate improvements in AD pathology following the administration of both orexigenic and anorexigenic compounds, highlighting the therapeutic potential of food intake-regulating peptides in neurodegenerative disorders.Graphical

Impaired Brain Functional Connectivity and Complexity in Mild Cognitive Decline

Impaired Brain Functional Connectivity and Complexity in Mild Cognitive Decline

Subventricular Accumulation of Cu in the Aging Mouse Brain Does Not Associate with Anticipated Increases in Markers of Oxidative Stress.

Natural aging is associated with mild memory loss and cognitive decline, and age is the greatest risk factor for neurodegenerative diseases, such as Alzheimer's disease. There is substantial evidence that oxidative stress is a major contributor to both natural aging and neurodegenerative disease, and coincidently, levels of redox active metals such as Fe and Cu are known to be elevated later in life. Recently, a pronounced age-related increase in Cu content has been reported to occur in mice and rats around a vital regulatory brain region, the subventricular zone of lateral ventricles. In our study herein, we have characterized lateral ventricle Cu content in a unique murine model of accelerated aging, senescence accelerated mouse-prone 8 (SAMP8) mice. Our results confirm an age-related increase in ventricle Cu content, consistent with the studies by others in wild-type mice and rats. Specifically, we observed Cu content to increase over the time frame 1 to 5 months and 5 to 9 months, but interestingly, no significant increase occurred between 9 and 12 months (although brain Cu content at 12 months was significantly elevated relative to 1 and 5 month-old animals). Despite the magnitude of Cu increase observed within the cells that comprise the subventricular zone of lateral ventricles (average 3 mM Cu, with isolated subcellular concentrations of 17 mM), we did not detect spectroscopic markers of thiol oxidation, protein aggregation, or lipid oxidation. The lack of evidence for oxidative stress in ex vivo animal tissue is in contrast to in vitro studies demonstrating that thiol, protein, and lipid oxidation is pronounced at these Cu concentrations. We suggest that our findings most likely indicate that the Cu ions in this brain region are sequestered in an unreactive form, possibly extended chains of Cu-thiolate complexes, which do not readily redox cycle in the aqueous cytosol. These results also appear to partially challenge the long-held view that age-related increases in brain metal content drive oxidative stress as we did not observe a concomitant association between age-related Cu increase and markers of oxidative stress, nor did we observe a net increase in Cu content between mice aged 9 and 12 months.

Introduction of a smart insulin pen in an elderly patient with type 1 diabetes mellitus

In elderly diabetes patients with an impaired cognitive function and activities of daily living, multiple daily insulin injection (MDI) therapy is associated with poor injection rates. However, patients with insulin-dependent conditions, such as type 1 diabetes, need to continue insulin therapy. Intermittently scanned continuous glucose monitoring (isCGM) and smart insulin pens have recently emerged as devices for blood glucose management. Smart insulin pens are devices that automatically record the insulin injection time and injection units of insulin and wirelessly transfer the data to a smartphone application. We herein report an elderly patient with type 1 diabetes who was treated with a smart insulin pen.An 84-year-old woman was diagnosed with type 1 diabetes at 45 years old and had been receiving MDI therapy. She had frequent unconscious hypoglycemia and thus had isCGM introduced at 80 years old. Her Mini-Mental State Examination score was 20 points, indicating mild cognitive decline, and isCGM revealed repeated hyperglycemia due to forgetting her insulin injection and hypoglycemia due to over-dose of insulin. When she was hospitalized for diabetic ketosis at 84 years old, a smart insulin pen was introduced. Following this introduction, her family and medical staff checked her insulin records and encouraged her to perform injections. She subsequently no longer experienced hyperglycemic crisis or severe hypoglycemia.Elderly patients with type 1 diabetes often have difficulty with self-management of MDI therapy. Smart insulin pens are expected to reduce the rate of forgetting insulin injections and improve injection rates.

Incidence of 12-month postoperative cognitive decline following regional vs. general anaesthesia in older patients undergoing hip fracture surgery: follow-up of the RAGA trial.

Data regarding the incidence of 12-month postoperative cognitive decline following regional or general anaesthesia in older patients undergoing hip fracture surgery remain observational. Compared with general anaesthesia, we hypothesised that regional anaesthesia would decrease the incidence of 12-month postoperative cognitive decline. This is substudy of a multicentre randomised trial of regional anaesthesia with no sedation vs. general anaesthesia with 12-month follow-up, conducted in nine university hospitals in south-eastern China. Patients aged ≥ 65 y with hip fractures requiring surgery were eligible for inclusion. The prespecified 1-year primary outcome was the incidence of postoperative cognitive decline at 12 months post-randomisation. Secondary outcomes included major or mild postoperative cognitive decline; changes in Mini-Mental State Examination; newly developed dementia; affective status; and health-related quality of life. We recruited 950 patients between October 2014 and September 2018 (n = 474 general and n = 476 regional), with the last participant interviewed in November 2019. A total of 293 patients (139 general vs. 154 regional) were included in the primary analysis of the 12-month outcome. Median (IQR [range]) age of patients was 78 (71-82 [65-96]) y and 217 (74.1%) were female. The incidence of cognitive decline at 12 months was 29.7% vs. 25.4% of patients allocated to general vs. regional anaesthesia, respectively (unadjusted OR 1.2 (95%CI 0.7-2.1), p = 0.43, Bayes factor = 0.28). Major cognitive decline developed in 8.6% vs. 8.5% of patients allocated to general vs. regional anaesthesia, respectively (unadjusted OR 1.0 (95%CI 0.4-2.4)). The incidence of 12-month postoperative cognitive decline was not significantly different in patients having general or regional anaesthesia for hip fracture surgery.

Longitudinal study of care needs and behavioural changes in people living with dementia using in-home assessment data

BackgroundPeople living with dementia often experience changes in independence and daily living, affecting their well-being and quality of life. Behavioural changes correlate with cognitive decline, functional impairment, caregiver distress, and care availability.MethodsWe use data from a 3-year prospective observational study of 141 people with dementia at home, using the Bristol Activities of Daily Living Scale, Neuropsychiatric Inventory and cognitive assessments, alongside self-reported and healthcare-related data.ResultsHere we show, psychiatric behavioural symptoms and difficulties in activities of daily living, fluctuate alongside cognitive decline. 677 activities of daily living and 632 psychiatric behaviour questionnaires are available at intervals of 3 months. Clustering shows three severity-based groups. Mild cognitive decline associates with higher caregiver anxiety, while the most severe group interacts more with community services, but less with hospitals.ConclusionsWe characterise behavioural symptoms and difficulties in activities of daily living in dementia, offering clinically relevant insights not commonly considered in current practice. We provide a holistic overview of participants’ health during their progression of dementia.

Bibliometric Analysis of Alzheimer's Disease and Depression.

The link between Alzheimer's disease and depression has been confirmed by clinical and epidemiological research. Therefore, our study examined the literary landscape and prevalent themes in depression-related research works on Alzheimer's disease through bibliometric analysis. Relevant literature was identified from the Web of Science core collection. Bibliometric parameters were extracted, and the major contributors were defined in terms of countries, institutions, authors, and articles using Microsoft Excel 2019 and VOSviewer. VOSviewer and CiteSpace were employed to visualize the scientific networks and seminal topics. The analysis of literature utilised 10,553 articles published from 1991 until 2023. The three countries or regions with the most publications were spread across the United States, China, and England. The University of Toronto and the University of Pittsburgh were the major contributors to the institutions. Lyketsos, Constantine G., Cummings, JL were found to make outstanding contributions. Journal of Alzheimer's Disease was identified as the most productive journal. Furthermore, "Alzheimer's", "depression", "dementia", and "mild cognitive decline" were the main topics of discussion during this period. Data were searched from a single database to become compatible with VOSviewer and CiteSpace, leading to a selection bias. Manuscripts in English were considered, leading to a language bias. Articles on "Alzheimer's" and "depression" displayed an upward trend. The prevalent themes addressed were the mechanisms of depression-associated Alzheimer's disease, the identification of depression and cognitive decline in the early stages of Alzheimer's, alleviating depression and improving life quality in Alzheimer's patients and their caregivers, and diagnosing and treating neuropsychiatric symptoms in Alzheimer. Future research on these hot topics would promote understanding in this field.

The influence of social support and demographics on depression and mild cognitive decline in devout elderly individuals

Introduction: Elderly individuals often experience psychosocial vulnerabilities that increase their risk for psychological disorders and are linked to cognitive impairments. This study explored how social support and demographic variables relate to the incidence of depression and cognitive decline among devout older adults. Methods: This cross-sectional observational study involved 125 senior participants from the Javanese Christian Church in Ambarrukma District of Yogyakarta. The research utilized demographic questionnaires, social support evaluations, surveys on religious attitudes, the Geriatric Depression Scale, and the MOCA-Ina tests. Data will undergo univariate and bivariate analyses and binary linear regression to evaluate odds ratios (OR), 95% confidence intervals (CI), and Pearson correlations between variables. Results: Elderly devout respondents (99.2%) who received good social support were more likely to experience no depression (47.9%) than those with poor social support (40.3%) (p=0.025; OR 0.182; 95% CI 0.038-0.873). The female gender suffered more from mild depression (p=0.021; OR 0.176; 95% CI 0.037-0.841) compared to men. Older adults with an education level of 7 years or more showed less mild cognitive impairment (p=0.044; OR 4.500; 95% CI 0.929-21.802). Conclusion: This study revealed that social support plays a role in modifying the incidence of depression in devout elderly individuals. The female gender suffered more from mild depression. Additionally, lower education levels were correlated with mild cognitive impairment. Further research with a more robust analysis with a larger sample size and consideration of other factors is necessary to confirm the causal relationships between social support and gender and depression.

Glial and synaptic biomarkers as early indicators of mild cognitive decline

AbstractBackgroundCognitive disorders are a growing cause of morbidity and mortality worldwide. Diagnostic approaches to improve early diagnosis of cognitive disorders are constantly being sought. The pathogenesis of cognitive impairment is multifactorial and complex. It is believed that microglial activation and synaptic disturbance are crucial mechanisms leading to disease progression thus study of the interrelationships of the proteins involved in these processes appears to be important. Chemokine CX3CL1 seems to play a pivotal role in the central nervous system and it is involved in microglia‐neuron communication, neuronal survival, synaptic plasticity, as well as neuronal excitability. Findings from preclinical studies on AD models have reported the crucial role of CX3CL1 in microglial activation, regulation of plaque load, and cognition. Neurogranin is considered, as a biomarker of early synaptic dysfunction in AD. Additionally, it may serve as a marker to predict disease progression. Therefore, we aimed to investigate and compare CX3CL1 and neurogranin (Ng) levels in CSF patients with mild cognitive decline (MCI) and cognitively normal subjects from the control group. We also assessed an association between CSF concentrations of CX3CL1, Ng, and neurochemical dementia biomarkers.MethodThe concentrations of CX3CL1, neurogranin as well as neurochemical dementia biomarkers, including amyloid beta 1‐42 (Aß‐42), amyloid beta 1‐40, Tau, as well as pTau181 were measured in cerebrospinal fluid patients with mild cognitive impairment and individuals without cognitive decline by multiplexing and enzyme‐linked immunosorbent techniques.ResultSignificantly higher CSF concentrations of CX3CL1 and neurogranin were found in MCI patients in comparison to subjects without cognitive decline. Furthermore, in the group of patients with MCI the CSF levels of CX3CL1 and Ng significantly correlated with Aβ‐42, and pTau181 proteins. Similarly, a significant association between neurogranin and Tau protein was observed. Additionally, a positive correlation between CSF levels of Ng and CX3XL1 was noticed.ConclusionOur findings indicate that both proteins CX3CL1, as well as neurogranin, could be applied as complementary early biomarkers for more accurate diagnosing and stratification of patients with cognitive decline.

The use of FDG PET in the assessment of dementia syndromes: numbers from a reference center in Recife, Brazil

AbstractBackgroundPositrons Emission Tomography associated with Computed Tomography – PET/CT using the 18F‐fluorodeoxyglucose is a well‐established exam for the context of dementia evaluation. However, FDG PET is a method still unavailable in most centers and diagnostic accuracy depends on the development of a flowchart that involves proper indication by clinicians and specialized evaluation by nuclear medicine specialists. Our study aims to investigate the indications of FDG PET in the differential diagnosis of dementia in a single center; secondarily, to evaluate how this method aided the diagnostic process.Methodsingle‐center, descriptive analysis of patients with an initial diagnosis of neuropsychiatric syndromes that underwent FDG PET between 2018‐2023. We used an Excel chart to register clinical data and diagnostic hypothesis, followed by the FDG PET results. The final classification of each patient’s clinical diagnosis and image diagnosis findings was: concordant, discordant and undetermined concordation.Result56 patients were included. The mean age was 71 years‐old and 55.36% were female. The diagnostic impression of the PET‐CT report of these cases showed 13 non‐specific changes in the metabolic view, 16 changes compatible with Alzheimer’s Disease (AD), 7 Lewy Bodies Dementia (LBD), 11 Frontotemporal dementia (FTD), 1 was associated with Mild Cognitive Decline (CLD). Furthermore, 7 of the reports were described as “Negative for dementia” and 1 as progressive supranuclear palsy (PSP). The main indications for PET‐CT scans were suspicion between the diagnosis of AD versus FTD and AD versus LBD. Suspicions for pseudodementia and other diseases progressing to cognitive impairment were also evaluated. Of the 56 patients in the sample, 14 (25.00%) of the clinical impressions were discordant with the results of the imaging exam, 24 (42.86%) were concordant and in 18 (32.14%) comparisons the exam pointed to indeterminate result.ConclusionIn this study, we observed that PET‐CT had the contributive potential to diagnostics of dementia in the majority of analyzed cases, in which it added value to initial clinical suspicions. In this sense, expanding data and carrying out new studies is still necessary.

The impacts of hospital admission in very late-onset schizophrenia-like psychosis: A case report.

Very late-onset schizophrenia-like psychosis (VLOSLP) is a psychotic disorder with an age of onset ≥60 years, and social isolation is a risk factor. Reports on the impact of interventions for isolation and loneliness on psychiatric symptoms in VLOSLP are limited. An 87-year-old woman, widowed and living alone, developed psychosis, including paranoia, erotomania, and visual hallucinations, at 84 years old during a period when her interactions with others were limited by the COVID-19 pandemic and osteoarthritis. She was eventually brought to our hospital with a local dementia outreach team. She was admitted and diagnosed with VLOSLP with mild cognitive decline through imaging and neuropsychological tests confirming the absence of dementia. Immediately after admission, her psychotic symptoms became inactive. She was transferred to another psychiatric hospital to prepare for her move to a long-term care facility because her psychosis was alleviated. During admission, she enjoyed the company of others and occupational therapy, and her score on the UCLA Loneliness Scale Version 3 improved from 44 at admission to 35 at discharge. The admission itself improved the patient's psychosis, which seemed to be related to the alleviation of isolation and loneliness.

Is a body mass index of less than 18.5 kg/m2 associated with an increased susceptibility to mild cognitive impairment? A cross-sectional study conducted in China

ObjectiveInvestigating the correlation between body mass index (BMI) and cognitive decline among elderly people in the Chinese community.DesignA non-random sampling method was employed to conduct a cross-sectional, mixed methods survey...

Post-COVID cognitive impairments: targets of neuropsychological rehabilitation

BACKGROUND: At the moment, a large number of scientific studies are devoted to the topic of post-COVID cognitive disorders, as well as to the study of the neurological and psychiatric consequences of COVID-19. However, the issues of describing the cognitive profile that is pathognomonic for a post-COVID patient, as well as the treatment and neurocorrection of emerging disorders are considered extremely rarely. AIM: The aim of this study is to compile a cognitive profile of a post-COVID patient and identify targets for neuropsychological rehabilitation. MATERIALS AND METHODS: A complete neuropsychological examination was carried out on 50 patients who had suffered moderate or mild COVID-19 no more than six months ago from the time of research. Used: MoCA test, clock drawing test, verbal association technique, FAB, G. Head test, test for understanding comparative constructions, “barrel and box” test, symbol-numeric coding test, asthenia rating scale (MFI-20), Hospital scale anxiety and depression. RESULTS: According to the results of screening scales, patients scored borderline between normal and mild (subjective) cognitive decline. No impairments in operational auditory-verbal and visual memory were detected. Low performance in the symbolic-numeric coding technique was revealed, combined with a deterioration in the understanding of logical-grammatical structures. These same scales have a direct correlation with the general level of cognitive integrity. High rates of anxiety and asthenia and low rates of depression were revealed. CONCLUSIONS: This cohort of patients was found to have mild cognitive deficits. A decrease in neurodynamic parameters and a violation of quasi-spatial concepts come to the fore. There are high rates of anxiety and asthenia with the leading mental component of asthenia, against the background of preserved motivation and low rates of depression. The targets of neurocorrection for these patients are: stability of attention, fluency of speech, speed of thinking, quasi-spatial concepts.