Search Results (95)

Background/Objectives: In the last decade, there has been a notable increase in the prevalence of cognitive decline among the elderly population. This phenomenon is further compounded by the concurrent rise in life expectancy, indicating a growing concern for the health and well-being of individuals in this demographic. Dementia has become a disease with a strong social impact, not exclusively limited to its health dimension. It is generally accepted that lifestyle factors and psychological attitudes toward life challenges may serve as protective mechanisms against pathological cognitive decline. The objective of this contribution is to evaluate the impact of lifestyle factors (e.g., physical activity, employment history, nutrition, technology use, etc.), stressors (e.g., illness, rare events, abandonments, home moving, etc.), and sociability (e.g., marriage, active friend network, children proximity, work relationships, etc.) at the onset of pathological cognitive frailty. Methods: In this study, a semi-structured interview was administered to 32 individuals over the age of 65 during their initial neuropsychological evaluation for suspected dementia. Results: Linear regressions with Mini Mental State Examination scores indicated that lifestyle and sociability factors offer a degree of protection against cognitive decline, while stressors were found to be unrelated to this phenomenon. Conclusions: The utilization of contemporary technologies, the possession of a driver’s license, and the maintenance of an active social network have been demonstrated to possess a high degree of predictive value with respect to cognitive reserve in the context of aging. Full article

Background/Objectives: Old age and cognitive impairment/dementia are risk factors for falling and fall-related injuries. We have, in a previous study in persons with cognitive impairment, shown that falls were associated with frailty, reduced physical fitness, and cognitive reduction. Falls were independent of the disorders causing the impaired functions. Because most falls are innocent, knowledge of predictors of fall-related injuries seems more clinically relevant than the predictors of falls. Predictors of falls and fall-related injuries are not necessarily identical. The aim of this follow-up study to our previous one in the same population was to explore predictors of fall-related injuries in fallers and compare these predictors with those of falls. Methods: This study and our previous study used data from the “The Norwegian Registry of Persons Assessed for Cognitive Symptoms” (NorCog), a Norwegian research and quality registry with a biobank. The registry included consecutive home-dwelling persons referred to Norwegian specialist healthcare units for assessment of cognitive decline. This study included 3774 persons from our previous study who experienced falls last year and compared persons with and without a fall-related injury. A fall-related injury was defined as admittance to a hospital for the injury. Results: The annual incidence of fall-related injuries in the fallers was 884/3774 (23.4%). Female sex, older age, lower BMI, in need of public health service and walking assistance, and low Hb and Ca were independent predictors of fall-related injuries, indicating reduced physical fitness and state of health and a high burden of comorbidity. Injuries were not associated with the degree of cognitive impairment or the dementia diagnosis. Conclusions: In home-dwelling persons with impaired cognitive functions and falls, fall-related injuries were associated with reduced physical fitness and state of health. In contrast to predictors of falls, neither the degree of cognitive impairment nor the dementia diagnosis was associated with fall-related injuries. The difference is comprehensible. Persons with cognitive impairment or dementia might have reduced power of judgment and be inattentive, unconcerned and careless, which increases the fall incidence but not the risk of injury once falling. Prevention of fall-related injuries should focus on relieving comorbidities, improving physical fitness and general health rather than on cognitive improvement. Full article

There is still a lack of effective therapies for Alzheimer’s disease (AD), the leading cause of dementia and cognitive decline. Identifying reliable biomarkers and therapeutic targets is crucial for advancing AD research. In this study, we developed an aggregative multi-filter gene selection approach to identify AD biomarkers. This method integrates hub gene ranking techniques, such as degree and bottleneck, with feature selection algorithms, including Random Forest and Double Input Symmetrical Relevance, and applies ranking aggregation to improve accuracy and robustness. Five publicly available AD-related microarray datasets (GSE48350, GSE36980, GSE132903, GSE118553, and GSE5281), covering diverse brain regions like the hippocampus and frontal cortex, were analyzed, yielding 803 overlapping differentially expressed genes from 464 AD and 492 normal cases. An independent dataset (GSE109887) was used for external validation. The approach identified 50 prioritized genes, achieving an AUC of 86.8 in logistic regression on the validation dataset, highlighting their predictive value. Pathway analysis revealed involvement in critical biological processes such as synaptic vesicle cycles, neurodegeneration, and cognitive function. These findings provide insights into potential therapeutic targets for AD. Full article

Background/Objectives: The annual incidence of falls is high in older adults with impaired cognitive function and dementia, and injuries have a detrimental effect on disability-adjusted life-years and public health spending. In this registry-based study, fall incidence and characteristics of the fallers were explored in a large population with cognitive impairment. Methods: NorCog, “The Norwegian Registry of Persons Assessed for Cognitive Symptoms”, is a national research and quality registry with a biomaterial collection. This study included 9525 persons from the registry who had answered the question about falls. Fall incidence was studied, and the characteristics of fallers and non-fallers were compared. Results: The annual fall incidence was 3774/9525 (39.6%). The incidence varied between types of dementia, from 22.4% in persons with the debut of Alzheimer’s disease before 65 years of age to 55.3% in persons with vascular dementia and with increasing degrees of cognitive impairment. A wide range of personal characteristics, symptoms, signs, laboratory tests, and physical, psychological, and cognitive tests differed between fallers and non-fallers, most in disfavour of the fallers. Age, reduced Personal Activities of Daily Living, reduced gait speed, delayed recall, use of a walking aid, and depression were independent predictors of falls. Conclusions: Among cognitively impaired persons with a history of falls, frailty was an independent predictor of falls. Neither the type of dementia nor the degree of cognitive impairment were independent predictors of falls. Prevention of frailty by physical training and social activity may be important in mitigating fall risk among older adults with impaired cognition. Full article

Background/Objectives: Dementia is a syndrome which involves cognitive and motor problems such as memory and motor control that impacts the individuals’ quality of life. In mental imagery (MI) technique, motor acts are mentally rehearsed without any overt body movements. The aim of this study was to investigate the effectiveness of MI on the quality of life, cognitive, and emotional status of older adults with an early stage of dementia. Methods: The present randomized controlled trial consisted of 160 participants. The sample from an Athens Day Care Center of the Alzheimer Association was randomized to (a) the MI and exercise group (intervention group, n = 55), (b) the only exercise group (1st control group, n = 52), and (c) the neither MI nor exercise group (2nd control group, n = 53). Participants engaged in a total of 24 physiotherapy sessions, each lasting approximately 45 min, scheduled twice weekly over a 12-week period. They performed three assessments: (a) one week prior to the program, (b) one and a half months, and (c) after the program. The intervention group performed a 30 min MI with exercise program content immediately following every physiotherapy exercise session. Walking While Talking Test (WWITT), the Euro-Qol 5-Dimensions 5-Level of severity scale (Euro-Qol 5D-5L scale), the Short-Form of Geriatric Depression Scale (SF-GDS), and the Short Anxiety Screening Test (SAST) were used to assess cognitive status, emotional status, and quality of life. Results: A total of 160 participants (43 men, 117 women, with MMSE M = 23.20 SD = 0.15) took part in this study in which most reported holding a university degree (n = 77), were married (n = 101), and had loss of memory as the 1st symptom of dementia (n= 117). The Friedman test revealed statistically significant differences across the three groups on (a) the WWITT_mistakes (X² = 14.95, df = 2, p = 0.001) and WWITT_time (X² = 13.35, df = 2, p = 0.01), (b) the total Euro-Qol 5D-5L scale (X² = 11.87.62, df = 2, p = 0.003) and quality of life on the measuring day (X² = 25.59, df = 2, p = 0.00), (c) the SF-GDS (X² = 6.54, df = 2, p = 0.038), and (d) the SAST (X² = 39.907.62, df = 2, p = 0.00). The Friedman test with post hoc Wilcoxon analysis revealed that the mean scores for the intervention group and the 1st control were significantly better than the 2nd control group in many dependent variables. Conclusions: The results indicate that incorporating MI can positively influence cognitive status, emotional status, and the quality of life in older adults diagnosed with early-stage dementia. Full article

Objectives: Variants in Cyclin F (CCNF) have been associated to amyotrophic lateral sclerosis (ALS) and/or frontotemporal dementia (FTD) in a group of cases. The objectives of this study were to determine the contribution of CCNF in a large cohort of Italian ALS patients, to look for genotype-phenotype correlation of the mutations and to evaluate the CCNF-associated clinical features. Methods: We applied next-generation sequencing technologies on 971 unrelated Italian ALS patients and we filtered results to look for variants in CCNF gene. Results: We identified 13 rare missense variants in 16 index cases (2 familial and 14 sporadic), with a cumulative mutational frequency of 1.6%. The most prevalent variant was p.Phe197Leu, found in three patients. The clinical presentation was heterogeneous, with a classic phenotype in eight patients, upper motor neuron dominant (UMN-D) phenotype in four patients, and flail arm in four patients. Clinical evaluation for cognitive impairment was performed in 13 patients using the Edinburgh Cognitive and Behavioural ALS Screen (ECAS) test, demonstrating that almost half of the patients (n = 6) had variable degrees of frontal dysfunction. Discussion: In our cohort, we observed CCNF variants in 1.6% of patients (16/971), a percentage similar to that found in other series. Clinical presentation is heterogeneous, but CCNF variants are significantly associated to cognitive impairment. Conclusions: Our study expands the CCNF genetic variant spectrum in a large cohort of Italian ALS patients. Further studies are needed to assess genotype-phenotype associations of CCNF variants and to specify the role of each variant, which are quite common, especially in sALS patients. Full article

Objective: Neurofilament light chain proteins (NfLs) are considered a promising biomarker of neuroaxonal damage in several neurological diseases. Their measurement in the serum and cerebrospinal fluid (CSF) of patients with dementia may be especially useful. Our aim was to compare the NfL measurement performance of two advanced technologies, specifically the Ella™ microfluidic platform and the Lumipulse™ fully automated system, in patients with cognitive disorders. Methods: Thirty subjects with neurodegenerative cognitive disorders (10 with Alzheimer’s Disease, 10 with Frontotemporal Dementia, and 10 with non-progressive Mild Cognitive Impairment) seen at the Cognitive Neurology Clinic of Modena University Hospital (Italy) underwent CSF and serum NfL measurement with both the Ella™ microfluidic platform (Bio-Techne, Minneapolis, MN, USA)) and the Lumipulse™ fully automated system for the CLEIA (Fujirebio Inc., Ghent, Belgium). Correlation and regression analyses were applied to assess the association between NfL concentrations obtained with the two assays in CSF and serum. The Passing–Bablok regression method was employed to evaluate the agreement between the assays. Results: There were high correlations between the two assays (r = 0.976, 95% CI. 0.950–0.989 for CSF vs. r = 0.923, 95% CI 0.842–0.964 for serum). A Passing–Bablok regression model was estimated to explain the relationship between the two assays, allowing us to switch from one to the other when only one assay was available. Conclusions: We found a good degree of correlation between the two methods in patients with neurocognitive disorders. We also established a method that will allow comparisons between results obtained with either technique, allowing for meta-analyses and larger sample sizes. Full article

Introduction: Atypical parkinsonisms (APs) present various symptoms including motor impairment, cognitive decline, and autonomic dysfunction. Olfactory loss (OL), being a significant non-motor symptom, has emerged as an under-evaluated, yet potentially valuable, feature that might aid in the differential diagnosis of APs. State of the art: The most pronounced OL is usually associated with Dementia with Lewy Bodies (DLB). While the view about the normosmic course of Multiple System Atrophy (MSA) remains unchanged, research indicates that mild OL may occur in a subset of patients with Progressive Supranuclear Palsy (PSP) and Corticobasal Degeneration (CBD). This might be linked to the deposition of abnormal protein aggregates in the central nervous system. Clinical significance: The aim of this review is to discuss the role of OL and its degree and pattern in the pathogenesis and course of APs. Olfactory testing could serve as a non-invasive, quick screening tool to differentiate between APs and project disease progression. Future directions: There is a need for further evaluation of this topic. This may lead to the development of standardized olfactory testing protocols that could be implemented in clinical practice, making differential diagnosis of APs more convenient. Understanding differences in the sense of smell could create an avenue for more targeted therapeutic strategies. Full article

Atrial fibrillation (AF) is the most common sustained arrhythmia in adults. The prevalence of both AF and dementia is steadily rising and is expected to rise further in the coming decades. There is increasing evidence to suggest an association between AF and various degrees of cognitive dysfunction, from mild cognitive impairment to severe dementia. In this review, we aimed to discuss the epidemiological aspects, pathophysiological mechanisms, role of neuroimaging, impact of treatment modalities, and clinical and socioeconomic impact of this association. Numerous observational studies and meta-analyses have revealed this association to exist in AF patients with and without a history of stroke, and the association also persists after adjusting for shared risk factors such as hypertension and diabetes mellitus. Various pathophysiological mechanisms have been proposed for this association, including silent cerebral infarcts, cerebral microbleeds, cerebral hypoperfusion, inflammation, and atherosclerosis. While neuroimaging findings have been utilized to suggest some of these pathophysiological mechanisms, more studies are needed to further elucidate this and to determine the potential role of neuroimaging in altering anticoagulation and other treatment decisions. Anticoagulants have shown effectiveness in reducing the rate of cognitive decline in AF patients; however, their role in low-risk AF patients remains under investigation. Even though AF patients receiving catheter ablation may have post-operative cognitive dysfunction in the short term, long-term follow-up studies have shown an improvement in cognitive function following ablation. Cognitive decline in AF patients often occurs with greater functional decline and other psychosocial impairments such as depression and anxiety and future research on this association must incorporate aspects of social determinants of health and associated outcomes. Full article

Subjective cognitive impairment in older persons has a substantial influence on their quality of life and can progress to serious illnesses such as dementia. Physical activity level can help prevent cognitive decline and improve cognitive performance. The aim of this study was to investigate the association between frequency of physical activity and subjective cognitive impairment in Spanish adults aged 65 and over, and to identify different risk factors. Using data from the EHSS20 survey, the study focused on 7082 participants who provided information on cognitive impairment and physical activity. Key predictor variables included age, gender, BMI, marital status, and education level. A significant relationship was found between BMI category and gender, with 66.5% of the population being overweight or obese. Men were more likely to be overweight than women. Socio-demographic factors such as educational level, marital status, and physical activity frequency showed dependent associations with sex. Women had a higher prevalence of subjective cognitive impairment than men. A strong association was found between frequency of physical activity and subjective cognitive impairment, with inactive older people having the highest prevalence of subjective cognitive impairment. Older women who engage in little physical exercise and have less education are at risk for subjective cognitive impairment. Furthermore, for both men and women, being overweight was associated with a more reduced risk than obesity. Significant relationships were also discovered between subjective cognitive impairment, frequency of physical exercise, gender, BMI, and degree of education. In conclusion, older, sedentary women with high BMI and less education are more likely to experience subjective cognitive impairment. Full article

This qualitative study investigates technology readiness, i.e., self-management, social support, and digital health literacy, in people with dementia (PwD). PwD are difficult to recruit; therefore, we used an empathic approach to recruit and conduct interviews. The interviews with seven participants with dementia and two informal caregivers, guided by the READHY framework, reveal nuanced insights into their experiences. Participants demonstrate varying degrees of self-management, with informal caregivers playing pivotal roles in facilitating activities and supporting overall well-being. Cognitive challenges, such as concentration and communication difficulties, are prevalent, highlighting the importance of robust support systems. Internal and external support networks significantly influence social integration, yet societal misconceptions impede inclusion, exacerbating feelings of isolation for both participants and caregivers. Limited interaction with technology is observed, primarily reliant on caregivers for assistance. Technology may hold potential for enhancing independence and alleviating caregiver burden. As an empathetic approach eased recruitment and communication with PwD, we recommend using this approach for future studies to include participants who otherwise would not be recruited. Given that the number of participants in this study is limited to only seven PwD with moderate to severe cognitive impairment, further investigation using mixed methods, including the READHY framework, and a larger number of participants is needed to examine the generalizability of the findings. Full article

Mild cognitive impairment (MCI) is a significant concern as it is a risk factor for AD progression, and early detection is vital in order to delay dementia onset and enable potential therapeutic interventions. Olfactory impairment is recognized as a predictive biomarker in neurodegenerative processes. The aims of this study were to explore the degree of entorhinal cortical atrophy (ERICA) and the severity of MCI symptoms; to analyze magnetic resonance imaging (MRI) results for the entorhinal cortex, parahippocampal gyrus, peri entorhinal cortex, and the cerebellar tentorium; and to perform a comprehensive neuropsychological and psychophysical assessment. The main results highlighted that in our sample—multidomain amnesic MCI patients with hyposmic symptomatology—we found that ERICA scores were associated with the severity of anxiety symptomatology. One possible hypothesis to explain this observation is that anxiety may contribute to neurodegenerative processes by inducing chronic stress and inflammation. Future research should consider the longitudinal development of neuropsychological scores, anxiety disorders, and brain atrophy to determine their potential predictive value for MCI progression. These findings suggest the importance of psychological factors in MCI progression and the utility of neuropsychological assessment alongside neuroimaging techniques for early detection and follow-up in MCI patients. Full article

Neurological damage is the pathological substrate of permanent disability in various neurodegenerative disorders. Early detection of this damage, including its identification and quantification, is critical to preventing the disease’s progression in the brain. Tau, glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL), as brain protein biomarkers, have the potential to improve diagnostic accuracy, disease monitoring, prognostic assessment, and treatment efficacy. These biomarkers are released into the cerebrospinal fluid (CSF) and blood proportionally to the degree of neuron and astrocyte damage in different neurological disorders, including stroke, traumatic brain injury, multiple sclerosis, neurodegenerative dementia, and Parkinson’s disease. Here, we review how Tau, GFAP, and NfL biomarkers are detected in CSF and blood as crucial diagnostic tools, as well as the levels of these biomarkers used for differentiating a range of neurological diseases and monitoring disease progression. We also discuss a biosensor approach that allows for the real-time detection of multiple biomarkers in various neurodegenerative diseases. This combined detection system of brain protein biomarkers holds significant promise for developing more specific and accurate clinical tools that can identify the type and stage of human neurological diseases with greater precision. Full article

Neuropathological assessment was conducted on 1630 subjects, representing 5% of all the deceased that had been sent to the morgue of Uppsala University Hospital during a 15-year-long period. Among the 1630 subjects, 1610 were ≥41 years of age (range 41 to 102 years). Overall, hyperphosphorylated (HP) τ was observed in the brains of 98% of the 1610 subjects, and amyloid β-protein (Aβ) in the brains of 64%. The most common alteration observed was Alzheimer disease neuropathologic change (ADNC) (56%), followed by primary age-related tauopathy (PART) in 26% of the subjects. In 16% of the subjects, HPτ was limited to the locus coeruleus. In 14 subjects (<1%), no altered proteins were observed. In 3 subjects, only Aβ was observed, and in 17, HPτ was observed in a distribution other than that seen in ADNC/PART. The transactive DNA-binding protein 43 (TDP43) associated with limbic-predominant age-related TDP encephalopathy (LATE) was observed in 565 (35%) subjects and α-synuclein (αS) pathology, i.e., Lewy body disease (LBD) or multi system atrophy (MSA) was observed in the brains of 21% of the subjects. A total of 39% of subjects with ADNC, 59% of subjects with PART, and 81% of subjects with HPτ limited to the locus coeruleus lacked concomitant pathologies, i.e., LATE-NC or LBD-NC. Of the 293 (18% of the 1610 subjects) subjects with dementia, 81% exhibited a high or intermediate level of ADNC. In 84% of all individuals with dementia, various degrees of concomitant alterations were observed; i.e., MIXED-NC was a common cause of dementia. A high or intermediate level of PART was observed in 10 subjects with dementia (3%), i.e., tangle-predominant dementia. No subjects exhibited only vascular NC (VNC), but in 17 subjects, severe VNC might have contributed to cognitive decline. Age-related tau astrogliopathy (ARTAG) was observed in 37% of the 1610 subjects and in 53% of those with dementia. Full article

There are two generic approaches to curing any medical condition. The first one treats every patient for all the known possible causes that contribute to pathogenesis; the second one individualizes potentially curative therapy by only identifying in each separate patient the components of pathogenesis that are actually operative and treating those. This article adopts the second approach for formulating a cure for Alzheimer’s dementia (AD). The components of AD’s pathogenesis are, in alphabetical order, as follows: circadian rhythm disturbances, depression, diabetes and insulin resistance, dyslipidemia, hypertension, inflammation, metabolic syndrome, mitochondrial dysfunction, nutritional deficiencies, TGF-β deficiency, underweight, vascular abnormalities, and Wnt/β-catenin deficiency. For each component, data are described that show the degree to which its prevalence is higher in patients with mild cognitive impairment (MCI) who did not revert to having normal cognition than in those who did because the former group is the pool of patients in which future AD may develop. Only addressing the components that are present in a particular individual potentially is a curative strategy. Published data indicate that curative therapy requires the number of such components that are addressed to be ≥3. Although structural brain changes cannot be directly addressed, the impaired neural tracts result from many of the reversible causal elements, so correcting them will benefit these tracts. Full article