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This review examines the potential of fasting-mimicking diets (FMDs) in preventing and treating Alzheimer’s disease (AD). FMDs are low-calorie diets that mimic the physiological and metabolic effects of fasting, including the activation of cellular stress response pathways and autophagy. Recent studies have shown that FMDs can reduce amyloid-beta accumulation, tau phosphorylation, and inflammation, as well as improve cognitive function in animal models of AD. Human studies have also reported improvements in AD biomarkers, cognitive functions, and subjective well-being measures following FMDs. However, the optimal duration and frequency of FMDs and their long-term safety and efficacy remain to be determined. Despite these uncertainties, FMDs hold promise as a non-pharmacological approach to AD prevention and treatment, and further research in this area is warranted.

Background The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) multimodal lifestyle intervention yielded cognitive and other health benefits in older adults at risk of cognitive decline. The two-year multinational randomized controlled LETHE trial evaluates the feasibility of a digitally supported, adapted FINGER intervention among at-risk older adults. Technology is used to complement in-person activities, streamline the intervention delivery, personalize recommendations, and collect digital biomarkers. Methods Trial includes older adults (60–77 years) with digital readiness/experience with smart devices and increased dementia risk but without substantial cognitive impairment. Participants are enrolled at four sites (Austria, Finland, Italy, Sweden). At baseline, participants were randomized 1:1 ratio to 1) intervention i.e., structured multimodal lifestyle program (including diet, exercise, cognitive training, vascular/metabolic risk management, social stimulation, sleep/stress management) where in-person activities led by professionals are supported with an Android mobile phone application developed by the consortium (the LETHE App); or 2) control i.e., self-guided program (regular health advice; simplified App with no personalized/interactive content). All participants wear smartwatches to gather passive data (e.g., physical activity, sleep). Primary outcomes are retention, adherence, and change in validated dementia risk scores. Secondary outcomes include changes in lifestyle, cognition, stress, sleep, health-related quality of life, and health literacy. Additional outcomes (exploratory) include e.g. participant experiences and dementia-related biomarkers (Alzheimer’s disease blood markers, neuroimaging). A sub-study explores the feasibility of novel interactive technology (audio glasses, social robot). Results Recruitment began in September 2022, and the last participant was randomized in June 2023. In total, 156 individuals were randomized (mean age 69 years, 65% women; balanced recruitment across the four sites). Vascular and lifestyle risk factors were common (e.g., 65% with hypertension, 69% with hypercholesterolemia, 39% physically inactive), indicating successful recruitment of a population with risk reduction potential. Trial will be completed by summer 2025. Retention until the first post-baseline visit at 6 months is high ( n  = 2 discontinued, retention 98.7%). Conclusion LETHE provides crucial information about the feasibility of technology and a digitally supported FINGER lifestyle program to promote brain health. Digital tools specifically designed for older adults could offer potential for large-scale, cost-effective prevention programs. Trial registration ClinicalTrials.gov (NCT05565170).

The rising prevalence of dementia is a major concern, with approximately 45% of cases linked to 14 modifiable risk factors. The European project LETHE aims to develop a personalized digital intervention model to delay or prevent cognitive decline through risk factor management. The objective of our study was to design a clinical trial platform for older individuals at risk of cognitive decline, including a mobile app for study participants and a clinical trial management system (CTMS) for health professionals. Using a user-centered design approach, workshops and feedback rounds involved potential participants representing the target group and professionals. The LETHE app's usability was assessed among 156 older adults enrolled in a 2-year multinational randomized controlled trial evaluating the feasibility of a digitally supported lifestyle program for dementia risk reduction. The randomized controlled trial is currently ongoing; the System Usability Scale (SUS) was administered 1 month after baseline to map first user experiences. Feedback on the LETHE CTMS was collected from 21 users. Of the 78 participants in the trial intervention group, 66 (85%) provided responses for the mobile app, with a median SUS score of 70 (IQR 55-82). Within the control group, 73% (57/78) of responses were received, with a median SUS score of 73 (IQR 63-90). For the CTMS, we received 71% (15/21) of responses, and the feedback was mostly positive. A ranking of the features that could be considered beyond state of the art showed that the integration of personalized activities (mean 2.23, SD 1.17) and real-time appointments (mean 2.46, SD 1.51) were considered the most novel ones. The LETHE app and CTMS were developed to support a personalized digital intervention method within a study involving 156 participants. Limitations include participants having digital literacy and internet access, potentially impacting the generalizability of the findings. Despite these limitations, positive feedback and high usability scores suggest promising potential for the LETHE app and CTMS in supporting personalized interventions to prevent cognitive decline in older adults.

Aim Dyslipidemia and cognitive decline are prevalent in older adults, with their incidence increasing with age. However, the relationship between serum lipid levels and cognitive dysfunction in geriatrics remains unclear, potentially influenced by sex differences. Methods This study evaluated serum lipid levels and cognitive functions in older adults using a large battery of neuropsychological tests. Dementia was staged with the Clinical Dementia Rating (CDR), classifying participants as cognitively healthy (CDR 0), mildly impaired (CDR 0.5), or with dementia (CDR ≥ 1). Results The study involved 1283 participants aged over 65 (466 men, 817 women; mean age 79.79 ± 5.93 years). Women had lower education levels, reduced autonomy in activities of daily living (ADL), but greater independence in instrumental ADL. Additionally, women exhibited lower glucose but higher levels of total cholesterol (TC), high-density lipoprotein (HDL-C), and low-density lipoprotein (LDL-C) compared to men. Subjects with CDR ≥ 1 had significantly poorer cognitive scores than those with CDR 0 or 0.5. No associations were found between lipid levels and cognition in the CDR 0 group. In men with CDR 0, HDL-C positively correlated with ACE-R Fluency. In the CDR 0.5 group, TC and HDL-C were linked to better cognitive performance. For CDR ≥ 1, TC and HDL-C were associated with improved cognition in women but linked to cognitive decline in men. Conclusion Elevated late-life cholesterol may protect cognitive function in healthy individuals and those with mild impairment, with a sex-specific impact in dementia, beneficial for women but detrimental for men.

Objective To examine the association between burden of multimorbidity and cognitive function in older adults with normal cognition or mild cognitive impairment (MCI). Methods Data from electronic health records of 898 individuals cognitively healthy or with MCI were included. Burden of multimorbidity was assessed using Cumulative Illness Rating Scale-Geriatrics (CIRS-G) total score, while cognitive function was evaluated using a comprehensive battery of neuropsychological tests. Age, sex, education, basic activities of daily living and instrumental activities of daily living scores, and total number of current medications were covariates. Spearmen’s correlations and multivariate regression models investigated the cross-sectional association between burden of multimorbidity and cognitive function. Results At a first exploratory analysis, higher CIRS-G score was significantly and negatively correlated with Addenbrooke’s Cognitive Examination Revised (ACE-R) total score, ACE-R Fluency Score, ACE-R Visual-spatial score, Digit Span Test Forward, Verbal Fluency Test, Visual Search Test and Coloured Progressive Matrices, while it was positively correlated with Trail Making Test A. Fitting fully-adjusted models and independent of all covariates, the inverse association between CIRS-G score and Verbal Fluency Test was confirmed ( P  <.001), while no significant association was found with other cognitive tests. Noteworthy, we excluded that specific disease categories could have driven the association. Conclusions The burden of multimorbidity is associated with impaired verbal phonemic fluency in individuals with normal cognition or MCI. Although further studies are required to confirm it, impaired verbal phonemic fluency may be an early sign of cognitive decline in older adults with multimorbidity, with potential implications for prevention strategies.

Background Skeletal muscle is the main source of circulating irisin, both at rest and during physical activity. Previous studies have suggested that irisin can improve cognitive abilities. Aims We explored whether six months of Tai Chi (TC) practice can modulate such a relationship in healthy older persons. Methods This is a prospective clinical study to evaluate the effects of TC practice as compared with low intensity exercise (LI) and no exercise (NE) control groups on plasmatic irisin levels and cognitive performance. Forty-two healthy older persons were stratified into three groups according to physical activities. Biochemical assay and cognitive functions were assessed at the baseline and after six months. Results A significant change was found in circulating irisin levels in TC as compared with NE group ( p  = 0.050) across time. At six months in TC group irisin levels significantly correlated with a verbal memory test ( p  = 0.013) controlled by age and education. Conclusion Our results suggest the potential benefits for cognitive health of TC practice by irisin levels modulation.

Background/Objectives: Malnutrition, systemic inflammation, and immune dysfunction are key determinants of adverse outcomes in older adults following acute illness. Composite biomarkers integrating these domains could enhance early risk stratification. This study investigates, for the first time in acute geriatric care, the prognostic value of the C-reactive protein–albumin–lymphocyte (CALLY) index—a composite marker of nutritional, inflammatory, and immune status—in predicting short-term survival. Methods: We retrospectively analyzed 264 patients admitted to the acute geriatrics ward of Santa Maria della Misericordia Hospital in Perugia. The CALLY index was calculated as: (Albumin × Lymphocytes)/(CRP × 104). The optimal prognostic cut-off was determined using receiver operating characteristic (ROC) curve analysis. Three-month survival was assessed by Kaplan–Meier analysis. Results: The cohort included 167 women (63.3%) and 97 men (36.7%), with a mean age of 88.0 ± 6.4 years. At 3-month follow-up, 80 patients (30.3%) had died. The CALLY index showed an area under the ROC curve of 0.647 (95% CI: 0.576–0.718; p < 0.001), with a cut-off of 0.055 (sensitivity: 68.5%, specificity: 46.3%). Among deceased patients, 42.5% had a CALLY index <0.055. After multivariable adjustment, a lower CALLY index remained independently associated with increased mortality (B = −0.805; OR = 0.45; 95% CI: 0.215–0.930; p = 0.031). Kaplan–Meier analysis demonstrated significantly higher survival in patients with a CALLY index ≥ 0.055 (Log-rank test: 13.71; p < 0.001). Conclusions: The CALLY index shows a modest but statistically significant discriminative ability for predicting short-term mortality in acutely ill older adults. As a simple, low-cost marker derived from routine laboratory tests, it holds potential for integration into clinical workflows to guide nutritional, metabolic, and prognostic management strategies in geriatric acute care.

Objective This study aims to examine the relationship between dysglycemia - also known as pre-diabetes or impaired glucose tolerance- and cognitive abilities in an older population living Mild Cognitive Impairment (MCI) and stratified by gender. Study design This is a retrospective study with data gathered from a large Italian clinical-based database. Main outcome measures The evaluation of cognitive performances by the Mini-Mental State Examination and the Addenbrooke’s Cognitive Examination Revised rating scale as tests of screening and a comprehensive neuropsychological evaluation of several cognitive areas. Results The study comprised 682 subjects (445 F/237 M) with a mean age of 76.08 ± 9.03 (range: 66–93) years. In all population, subjects with dysglycemia 193 (28.3%) had significantly poorer performance in memory ( p  = 0.006) and logic reasoning ( p  = 0.007) when compared with subjects without dysglycemia. The linear regression analyses revealed significant differences in the correlates of cognitive domains between gender groups. Independent of multiple covariates, women with dysglycemia showed worse performances in attention and short-term memory domains as compared with men. Even in the absence of dysglycemia women were more likely to show lower score in screening test of general cognition and attention. Conclusions Our findings suggest that dysglycemia in older individuals with MCI is associated with declines in specific cognitive domains, potentially influenced by gender. Implementing a comprehensive approach involving risk stratification and preventive strategies may be more effective in averting further cognitive decline in this high-risk population.

Background The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) multimodal lifestyle intervention yielded cognitive and other health benefits in older adults at risk of cognitive decline. The two‐year multinational randomized controlled LETHE trial evaluates the feasibility of a digitally supported, adapted FINGER intervention among at‐risk older adults. Technology is used to complement in‐person activities, for the intervention delivery, personalize recommendations, and collect digital biomarkers. Method Trial includes older adults (60‐77 years) with digital readiness and increased dementia risk but without substantial cognitive impairment. Participants are enrolled at four sites (Austria, Finland, Italy, Sweden). At baseline, participants were randomized 1:1 ratio to 1) intervention i.e., structured multimodal lifestyle program (including diet, exercise, cognitive training, vascular/metabolic risk management, social stimulation, sleep/stress management) where in‐person activities led by professionals are supported with an Android mobile phone application developed by the consortium (the LETHE App); or 2) control i.e., self‐guided program (regular health advice, simplified App with no personalized/interactive content). All participants wear smartwatches to gather passive data (e.g., physical activity, sleep). Primary outcomes are retention, adherence, and change in validated dementia risk scores. Secondary outcomes include changes in lifestyle, cognition, stress, sleep, health‐related quality of life, health literacy. Additional outcomes (exploratory) include e.g., participant experiences and dementia‐related biomarkers (Alzheimer’s disease blood markers, neuroimaging). A sub‐study explores the feasibility of novel interactive technology (audio glasses, social robot). Results Recruitment began in September 2022, and the last participant was randomized in June 2023. In total, 156 individuals were randomized (mean age 69 years, 65% women; balanced recruitment across the four sites). Vascular and lifestyle risk factors were common (e.g., 65% with hypertension, 69% with hypercholesterolemia, 39% physically inactive), indicating successful recruitment of a population with risk reduction potential. Trial will be completed by summer 2025. Retention until the first post‐baseline visit at 6 months is high (n = 2 discontinued, retention 98.7%). Latest progress of the trial will be presented. Conclusion LETHE provides crucial information about the feasibility of technology and a digitally supported FINGER program to promote brain health. Digital tools specifically designed for older adults could offer potential for large‐scale, cost‐effective prevention programs.

Background: Dementia is a priority for global public health. The management of behavioral and psychological symptoms of dementia (BPSD) is one of the highest ongoing challenges and needs new approaches. The special care unit for people with dementia and BPSD (SCU-B) is viewed in this context as a further medical intervention. Aim: this study aims to explore SCU-B units in order to describe their main characteristics in relation to different implementation contexts, identify the characteristics of their replicability, and examine the social innovation elements promoted by SCU-B units. Method: This qualitative study is based on focus groups (FGs) and interviews involving nine international centers. Five of the centers have a memory clinic unit and SCU-B, compared with six that only have a memory clinic unit. A total number of 18 FGs were held, which altogether involved 164 participants. All data were transcribed verbatim and analyzed by means of a content analysis and a SWOT (strengths, weaknesses, opportunities, and threats) analysis. Results: The qualitative analysis offers a vision of the SCU-B model as an innovative care unit for BPSD, promoting social innovation in the long-term care (LTC) sector. This system mainly targets people with dementia and BPSD and their informal caregivers but encourages collaboration between dementia care stakeholders at the micro and meso levels. Conclusions: Specific characteristics of the country’s LTC systems and the organization of specialized units are determinants for the success of the SCU-B experience. The replicability of the entire SCU-B model was considered low; however, the implementation of single elements composing the SCU-B model may foster innovation. This study provides relevant suggestions on how to implement the SCU-B unit and innovative solutions for dementia care.