Search Results (104)

Background/Objectives: Healthy ageing, focused on maintaining daily autonomy and cognitive function despite chronic comorbidities, poses a challenge for public health systems, especially for those aged ≥80, given the expected increase in this population. Promoting a healthy lifestyle in this group is essential to achieving this goal, with primary care services playing a key role in this effort. Therefore, our objective was to profile the participants based on these characteristics. Methods: The study included 222 non-institutionalized, dementia-free individuals (mean age 84.58 ± 3.72 years, 56.3% women) recruited from a primary healthcare service. Data were collected from medical records and interviews, including the cognitive Pfeiffer test, the functional Barthel index (BI), and ad hoc questionnaires (for lifestyle variables). Latent profiling analysis (LPA) was used to classify the participants. Results: The participants reported social support (97.7%), low-risk alcohol consumption (94.6%), adherence to the Mediterranean diet (85.1%), physical activity (74.8%), and never smoking (72.5%). Hypertension (86.5%), cataracts (74.3%), and osteoarticular diseases (68.5%) were the most frequent chronic conditions. Women showed a significantly different distribution of certain variables and a higher number of comorbidities (6.34 ± 2.38) than men (5.58 ± 2.44) (p = 0.019). After LPA, we found that 38.29% of individuals met characteristics compatible with healthy ageing, predominantly male (60%); the association of a high probability of cognitive impairment with a high degree (severe or total), exhibited by the profiles likely >85% women (18.5% of individuals); physical activity, smoking, osteoporosis, anxiety, COPD, chronic kidney disease (CKD), and creatinine blood levels exhibited statistical differences between profiles; and the probability of dependence severity was associated with an increase in age, although cognitive status conservation was associated being male. Conclusions: The studied +80 group seems to follow a healthy lifestyle, as self-reported. Women fare worse than men in resilient ageing. While common factors related to dysfunctionality did not differentiate between profiles, CKD, an increasingly common age-related condition, did. Full article

Background/Objectives: Mild Cognitive Impairment (MCI) represents a critical transition stage between normal aging and dementia, with executive dysfunction playing a key prognostic role. Traditional neuropsychological tests show limited ecological validity and may fail to detect early executive deficits. Virtual Reality (VR) offers an innovative alternative by reproducing everyday situations in realistic environments. This study investigated whether the Picture Interpretation Test 360° (PIT 360°), a VR-based assessment, can (1) discriminate between MCI patients and healthy controls (HCs); (2) identify executive dysfunction within the MCI group; and (3) correlate with standard neuropsychological measures. Methods: One hundred and one participants aged ≥65 years (53 MCI, 48 HCs) underwent a comprehensive neuropsychological assessment and PIT 360° evaluation. The PIT 360° requires interpreting a complex scene in a 360-degree virtual environment. Hierarchical linear regression, Receiver operating characteristic (ROC) curve analysis, and binary logistic regression were performed to examine group differences and diagnostic accuracy. MCI patients were stratified based on their performance on the Modified Five Point Test to identify visuospatial dysexecutive deficits. Results: MCI patients showed significantly longer PIT 360° completion times than HCs (92.6 vs. 65.3 s, p = 0.006), independent of age. MCI patients with visuospatial dysexecutive deficits exhibited the most severe deficits (median = 105 s, p = 0.017 vs. HCs). ROC analysis revealed adequate discriminative ability (AUC = 0.64, 95% CI [0.53, 0.75]) with a preliminary, sample-derived cut-off at ≥22 s, yielding high sensitivity (86.5%) but low specificity (42.6%). This threshold requires validation in independent samples. PIT 360° completion time correlated significantly with visuospatial executive functions, visual memory, and verbal fluency. Conclusions: The PIT 360° effectively screens for visuospatial executive dysfunction in MCI with high sensitivity, making it suitable for ruling out clinically significant impairment. Its ecological validity, brief administration, and correlations with traditional measures support integration into routine clinical practice for early detection and rehabilitation planning. Full article

Background: Mild cognitive impairment (MCI) is a high-risk prodromal stage of dementia. While tablet/computer-based computerized cognitive training (CCT) is widely used, its efficacy and gamification’s role need clarification. Objective: This study aimed to evaluate the effect of tablet/computer-based CCT on global cognition in older adults with MCI and explore the impact of gamification. Methods: We systematically searched five databases for RCTs (through October 2025) involving individuals aged ≥55 with MCI. The intervention was task-based CCT via tablets/computers. Primary outcome was global cognition. We used random-effects meta-analysis and subgroup analyses. Results: Nineteen RCTs (1013 participants) were included. CCT demonstrated a significant, moderate positive effect on global cognition (Hedges’ g = 0.57, 95% CI [0.36, 0.78]). A trend suggesting greater benefits with higher gamification was observed: high (g = 0.71), medium (g = 0.46), and low (g = 0.45) degrees. However, subgroup differences were not statistically significant (p = 0.4333). Results were robust in sensitivity analyses. Conclusions: Tablet/computer-based CCT effectively improves global cognition in MCI. The potential additive value of gamification highlights its promise for enhancing engagement and effects, warranting further investigation in larger trials. This systematic review was registered with PROSPERO (CRD420251231618). Full article

Pathogenic GRN variants that reduce progranulin (PGRN) levels cause frontotemporal dementia (FTD). To facilitate model development, we generated induced pluripotent stem cells (iPSCs) from dermal fibroblasts of two family members carrying the GRN c.1009C>T (p.Q337X) pathogenic variant—one symptomatic and one asymptomatic—as well as a non-carrier first-degree relative serving as a genetically matched control. The obtained iPSC lines were validated for pluripotency markers (Nanog, Sox2, Oct4, and TRA1-1-81), genomic integrity, and differentiation potential. The obtained iPSC lines were subsequently directed toward neuroepithelial stem (NES) cells. NES identity was confirmed by the expression of lineage-specific markers, including Nestin and Sox2 (assessed by immunocytochemistry), as well as SOX1, PLAGL1, and MKI67 (evaluated by real-time PCR). Furthermore, GRN mRNA levels were significantly reduced in iPSC and NES lines derived from mutation carriers compared to control cells. The established iPSC and NES cell lines represent a platform for modeling progranulin-deficient FTD. The symptomatic and asymptomatic carrier-derived lines obtained from the same family offer a unique opportunity to study disease progression across clinical phases. The control line, derived from a related (first-degree) non-carrier, minimizes genetic background variability. Their utility of the established cell lines extends to therapeutic drug screening and further differentiation into neuronal, non-neuronal, and organoid models. Full article

Inactivity and increases in psychological and behavioral symptoms are common for people with dementia, and current assessment relies on proxy-rated tools. We investigate the feasibility and adherence of the use of sensor technology by exploring the relationship between daytime activity and sleep quality. For a total of 42 day–night data pairs in nursing home residents with dementia (N = 11), Garmin Vivoactive5 and Somnofy monitored continuous physical activity levels, sleep efficiency (SE), sleep score, sleep regularity index (SRI), and wake after sleep onset (WASO). Using the Spearman coefficient, we explored correlations between digital and proxy-rated tools (Personal Self Maintenance Scale (PSMS) and Neuropsychiatric Inventory–Nursing Home version (NPI-NH)) and the relationships between the digital biomarkers (SE, SRI, WASO, sleep score, physical activity). Participants (mean age 84 years) had moderate to severe degrees of dementia. Daytime activity levels correlated to sleep quality parameters WASO (−0.34, p = 0.03), and SRI (0.43, p = 0.01), and traditional sleep measures were associated with digital biomarkers (WASO/NPI-NH-K, p = 0.03). We found a relationship between daytime activity and sleep quality; however, the bidirectional relationship remains ambiguous and should be further investigated. The use of sensing technologies for people with dementia residing in a nursing home is feasible, although not without limitations, and has the potential to identify subtle changes, improving clinical assessment and the corresponding care recommendations. Full article

Background: Dementia is a progressive neurodegenerative condition that impairs cognitive functions such as memory, language comprehension, and problem-solving. Assistive technologies can provide vital support at various stages of dementia, significantly improving the quality of life by aiding daily activities and care. However, for these technologies to be effective and widely adopted, a human-centred design (HCD) approach is of consequence for both their development and evaluation. Objectives: This scoping review aims to explore how HCD principles have been applied in the design of assistive technologies for people with dementia and to identify the extent and nature of their involvement in the design process. Eligibility Criteria: Studies published between 2017 and 2025 were included if they applied HCD methods in the design of assistive technologies for individuals at any stage of dementia. Priority was given to studies that directly involved people with dementia in the design or evaluation process. Sources of Evidence: A systematic search was conducted across five databases: Web of Science, JSTOR, Scopus, and ProQuest. Charting Methods: Articles were screened in two stages: title/abstract screening (n = 350) and full-text review (n = 89). Data from eligible studies (n = 49) were extracted and thematically analysed to identify design approaches, types of technologies, and user involvement. Results: The 49 included studies covered a variety of assistive technologies, such as robotic systems, augmented and virtual reality tools, mobile applications, and Internet of Things (IoT) devices. A wide range of HCD approaches were employed, with varying degrees of user involvement. Conclusions: HCD plays a critical role in enhancing the development and effectiveness of assistive technologies for dementia care. The review underscores the importance of involving people with dementia and their carers in the design process to ensure that solutions are practical, meaningful, and capable of improving quality of life. However, several key gaps remain. There is no standardised HCD framework for healthcare, stakeholder involvement is often inconsistent, and evidence on real-world impact is limited. Addressing these gaps is crucial to advancing the field and delivering scalable, sustainable innovations. Full article

Background: The voxel-based specific regional analysis system for Alzheimer’s disease (VSRAD) allows quantitative evaluation of the degree of an individual’s brain atrophy through statistical comparison of brain magnetic resonance imaging (MRI) of their brain to a normative database of healthy Japanese individuals. Currently, the VSRAD is used in routine clinical practice in the diagnosis of Alzheimer’s disease (AD) and dementia with Lewy bodies (DLB). Recent studies using VSRAD have explored its utility in the assessment of brain atrophy associated with various conditions, including diabetes, oral health status, and olfactory dysfunction. This review summarizes the principles of the VSRAD and its foundational method, voxel-based morphometry (VBM), and their clinical and research applications. Methods: This narrative review was conducted by performing a literature search of PubMed to identify articles regarding VBM and the VSRAD that were published between 2005 and 2025. Results: VSRAD yields four indices for quantifying the severity and extent of gray matter atrophy, especially in the medial temporal lobe. Studies have demonstrated its high diagnostic accuracy in distinguishing among AD, mild cognitive impairment (MCI), and DLB. Furthermore, it is correlated with neuropsychological test scores and has been applied to evaluate brain changes associated with diabetes, olfactory dysfunction, and physical inactivity. Motion-corrected MR images, which utilize AI techniques, have also been validated using VSRAD-derived metrics. Conclusions: Quantifying brain atrophy using the VSRAD allows objective evaluation and facilitates the investigation of its association with various diseases. Specifically, VSRAD can be considered a useful adjunctive tool for diagnosing AD and DLB. Full article

Cerebral perfusion single-photon emission computed tomography (SPECT) is a nuclear medicine imaging technique that uses radiopharmaceuticals that selectively accumulate in the brain. However, cerebral perfusion SPECT is typically interpreted through visual assessment, making the results susceptible to observer subjectivity and varying levels of experience. The easy Z-score Imaging System (eZIS) is a software that quantitatively analyzes cerebral perfusion SPECT images obtained using 99mTc-ECD by comparing them with a normal database and applying Z-scores for quantification. The eZIS received regulatory approval in January 2015 and is currently used as an auxiliary tool for clinical diagnosis. The eZIS aids in diagnosing Alzheimer’s disease by quantifying the degree of cerebral blood flow reduction in the posterior cingulate gyrus, precuneus, and parietal lobe, which are characteristic regions affected by the disease. Additionally, it can assist in diagnosing Lewy body dementia by evaluating the “cingulate island sign,” a characteristic finding in which cerebral blood flow in the posterior cingulate gyrus and precuneus is relatively preserved compared with that in the occipital lobe. eZIS is thus extremely useful for dementia diagnosis. Full article

Alzheimer’s disease is the most widespread neurodegenerative disease in the world. Galantamine hydrobromide (GH) is one of the drugs used to treat mild to moderate dementia of the Alzheimer type. Due to the fact that the specificity of the disease requires maximally facilitated intake, orodispersible films present such an opportunity. In the present study orodispersible films based on poly(2-ethyl-2-oxazoline) as well as partially hydrolyzed poly(2-ethyl-2-oxazoline) were prepared and studied as delivery systems for GH. Two samples of partially hydrolyzed PEtOx were synthesized—one of relatively low degree of hydrolysis and another one of relatively high degree of hydrolysis, and studied by Nuclear Magnetic Resonance (NMR). Cytotoxicity assay was performed that validated the low hydrolyzed derivative as biocompatible polymer that maintained desirable physicochemical characteristics without compromising the safety, thereby it was selected for further research. The films were prepared by the solution casting method and characterized by different methods. FTIR was used to determine the potential interactions between the galantamine molecule and the film components. Based on the Thermogravimetric Analysis (TGA) conducted, it was concluded that all films were sufficiently thermally stable, as the component decomposition stage (after initial solvent removal) began above 180 °C. The polymer films were further characterized with the determination of Shore hardness and the results showed that the films containing glycerol as a plasticizer exhibited higher hardness compared to those with PEG as a plasticizer. The disintegration time of the films was determined visually using Petri dishes and it was found that the films disintegrated within the range of 0.52 to 1.58 min, fully meeting the pharmacopoeial requirements. GH release profiles in PBS at 37 °C were obtained, and it was found that by the second minute, 80–90% of the drug were released from the different films, and the release followed an anomalous diffusion mechanism (Case II). Full article

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