Focus on senescence: Clinical significance and practical applications.

The older population is increasing worldwide, and life expectancy is continuously rising, predominantly thanks to medical and technological progress. Healthspan refers to the number of years an individual can live in good health. From a gerontological viewpoint, the mission is to extend the life spent in good health, promoting well-being and minimizing the impact of aging-related diseases to slow the aging process. Biologically, aging is a malleable process characterized by an intra- and inter-individual heterogeneous and dynamic balance between accumulating damage and repair mechanisms. Cellular senescence is a key component of this process, with senescent cells accumulating in different tissues and organs, leading to aging and age-related disease susceptibility over time. Removing senescent cells from the body or slowing down the burden rate has been proposed as an efficient way to reduce age-dependent deterioration. In animal models, senotherapeutic molecules can extend life expectancy and lifespan by either senolytic or senomorphic activity. Much research shows that dietary and physical activity-driven lifestyle interventions protect against senescence. This narrative review aims to summarize the current knowledge on targeting senescent cells to reduce the risk of age-related disease in animal models and their translational potential for humans. We focused on studies that have examined the potential role of senotherapeutics in slowing the aging process and modifying age-related disease burdens. The review concludes with a general discussion of the mechanisms underlying this unique trajectory and its implications for future research.

Aberrant telomeric structures and serum markers of telomere dysfunction in healthy aging: a preliminary study.

Telomeres undergo a progressive shortening process as individuals age, and it has been proposed that severely shortened and dysfunctional telomeres play a role in the aging process and the onset of age-related diseases in human beings. An emerging body of evidence indicates that the shortening of telomeres in cultured human cells is also influenced by other replication defects occurring within telomeric repeats. These abnormalities can be detected on metaphase chromosomes. Recent studies have also identified a set of serological markers for telomere dysfunction and DNA damage (elongation factor 1α [EF-1α], stathmin, and N-acetyl-glucosaminidase). With this study, the correlation between telomere abnormalities (by FISH) and these biomarkers as measured in blood serum (by ELISA) from a cohort of 22 healthy subjects at different ages (range 26-101 years) was analyzed. A strong positive correlation between aging and the presence of aberrant telomere structures, sister telomere loss (STL), and sister telomere chromatid fusions (STCF) was detected. When serum markers of telomere dysfunction were correlated with telomere abnormalities, we found that stathmin correlated with total aberrant telomeres structures (r = 0.431, p = 0.0453) and STCF (r = 0.533, p = 0.0107). These findings suggest that serum stathmin can be considered an easy-to-get marker of telomere dysfunction and may serve as valuable indicators of aging.

Tai chi, irisin and cognitive performance: a clinical and biological investigation in older adults.

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.

Dysglycemia, gender, and cognitive performance in older persons living with mild cognitive impairment: findings from a cross-sectional, population-based study.

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.

Effectiveness and Satisfaction with Telemedicine in Geriatric Patients at High Risk of Fragility Fractures.

Background: Telemedicine has increasingly widespread to improve the monitoring of patients with chronic diseases. Secondary prevention of fragility fractures is an urgent matter to be addressed by means of available technology, although supported by little evidence so far. We investigated the feasibility, efficacy, and satisfaction of managing older adults at high risk of fragility fractures during the COVID-19 lockdown. Methods: During the period January to July 2021, a prospective observational study for safety and adherence purposes was conducted among older adults (n = 407) with ongoing treatments for secondary prevention of fragility fractures. The study procedures comply with national and regional resolutions related to telemedicine service (TS), including equipment, staff behaviors, and patient reports. Results: A majority (86.48% [n = 352]) of the eligible patients joined the remote visits, mainly women (88.2%), 81.4 ± 8.8 years of age, 49.6% independent in 5 out of 6 BADL, despite high comorbidity (4.9 ± 1.5), and polypharmacy (4.9 ± 3.1). Almost all were on second-line antifracture treatments (95.58%) due to previous major (84.03%) and minor (42.5%) fragility fractures. About 58% reported good and very good reliability of the internet network, allowing easy access to the TS platform, and 54% declared the degree of satisfaction with TS as good and very good. About 75% of clinicians acknowledged the efficacy of TS and expressed willingness to recommend the use of TS to colleagues. Ultimately, 68% of specialists defined the time allocated for patients' remote visits as acceptable. Conclusion: TS may be an opportunity to improve the availability of appropriate health care services to satisfy patients' needs and optimize health care resource allocation.

BPSD Patterns in Patients With Severe Neuropsychiatric Disturbances: Insight From the RECAGE Study.

OBJECTIVE: Behavioral and psychological symptoms of dementia (BPSD) profiles vary depending on etiology in patients with mild-to-moderate BPSD. It is not known if similar differences exist in patients with severe BPSD. METHODS: We analyzed data collected at baseline in 398 patients with severe BPSD (NPI ≥ 32) and defined diagnosis of dementia (Alzheimer's disease [AD] 297; frontotemporal dementia [FTD] 39; Lewy body disease/Parkinsonian dementia [LBD/PD] 31; and vascular dementia [VD] 31) included in the European multicenter cohort RECAGE. RESULTS: Mean total NPI was 52.11 (18.55). LBD/PD patients demonstrated more hallucinations, more anxiety and more delusions than patients with other dementia. FTD patients had less delusions and more disinhibition than patients with other neurodegenerative disorders. These profiles overlapped partially with those reported in the literature in patients with less severe symptoms. CONCLUSION: Patients with severe BPSD display different and specific profiles of neuropsychiatric symptoms depending on dementia etiology.

Hypomagnesemia and incident delirium in hospitalized older persons.

BACKGROUND: Altered serum magnesium (Mg) levels in older persons have been hypothesized to have a role in predicting hospitalization and mortality. Hypomagnesemia and delirium are frequent problems in older patients, but no study has evaluated such an association in acute geriatric setting. AIMS: We investigated the impact of hypomagnesemia on the incidence of delirium in an acute geriatric setting. METHODS: This retrospective study was conducted on 209 older hospitalized patients. All subjects underwent a comprehensive geriatric assessment. Mg was measured in serum by routine laboratory methods. The presence of incident delirium was determined by the 4AT screening tool. A logistic regression model was used to assess the association between serum Mg and delirium controlling for multiple covariates. RESULTS: 209 patients (77.9% women) were included in the study. The mean age of the participants was 85.7 ± 6.50 years (range 65-100). 27 subjects (12.9%) developed delirium during the hospitalization, with no difference between genders. Subjects with delirium had lower serum magnesium levels than those without (1.88 ± 0.34 versus 2.04 ± 0.28; p = 0.009). Delirium risk was significantly higher in patients with lower serum magnesium levels (OR 5.80 95% CI 1.450-23.222; p = 0.013), independent of multiple covariates. CONCLUSION: Our data show that low serum Mg level is a good predictor of incident delirium in acute geriatric settings. Present findings have relevant implications for clinical management, highlighting the need for analyzing Mg concentration carefully. Whether Mg supplementation in patients with hypomagnesemia could lead to delirium prevention and/or control needs further investigation.

The correlates of post-surgical haematoma in older adults with proximal femoral fractures.

BACKGROUND: Little is known about the incidence of haematoma, and clinical correlates among orthogeriatric patients. AIMS: This study aims to describe the incidence of haematoma after surgical repair of hip fracture and to identify the clinical correlates of haematoma among orthogeriatric patients. METHODS: Two orthopaedic surgeons and a dedicated operator using ultrasound technique, each other in blindness, evaluated 154 orthogeriatric patients during their hospital stay. All patients received a comprehensive geriatric assessment. We investigated the concordance between clinical diagnosis and ultrasound detection of haematoma, and then we explored the clinical correlates of the onset of post-surgical haematoma. RESULTS: Blood effusion at the surgical site was detected in 77 (50%) patients using ultrasound technique; orthopaedic surgeons reached a clinical agreement about post-surgical haematoma in 18 (23%) patients. The sensitivity of clinical evaluation was 0.66, and the specificity was 0.70. Independent of age, clinical, pharmacological, and surgical confounders, proton pump inhibitors (PPIs) were associated with post-surgical haematoma (OR 2.28; 95% CI 1.15-4.49). A tendency towards association was observed between selective serotonin reuptake inhibitors and post-surgical haematoma (OR 2.10; 95% CI 0.97-4.54), CONCLUSIONS: Half of older patients undergoing surgical repair of proximal femoral fracture develop a post-surgical haematoma. Clinical assessment, even if made by senior orthopaedic surgeons, underestimates the actual occurrence of post-surgical haematoma compared to ultrasound detection. Ultrasound technique may help to detect haematoma larger than 15 mm better than clinical assessment. PPIs's use is a risk factor for post-surgical haematoma independent of several medical and surgical confounders.

Italian guidance on Dementia Day Care Centres: A position paper.

Dementia Day Care Centres (DDCCs) are defined as services providing care and rehabilitation to people with dementia associated with behavioural and psychological symptoms (BPSD) in a semi-residential setting. According to available evidence, DDCCs may decrease BPSD, depressive symptoms and caregiver burden. The present position paper reports a consensus of Italian experts of different disciplines regarding DDCCs and includes recommendations about architectural features, requirements of personnel, psychosocial interventions, management of psychoactive drug treatment, prevention and care of geriatric syndromes, and support to family caregivers. DDCCs architectural features should follow specific criteria and address specific needs of people with dementia, supporting independence, safety, and comfort. Staffing should be adequate in size and competence and should be able to implement psychosocial interventions, especially focused on BPSD. Individualized care plan should include prevention and treatment of geriatric syndromes, a targeted vaccination plan for infectious diseases including COVID-19, and adjustment of psychotropic drug treatment, all in cooperation with the general practitioner. Informal caregivers should be involved in the focus of intervention, with the aim of reducing assistance burden and promoting the adaptation to the ever-changing relationship with the patient.

An ontology-based approach for modelling and querying Alzheimer's disease data.

BACKGROUND: The recent advances in biotechnology and computer science have led to an ever-increasing availability of public biomedical data distributed in large databases worldwide. However, these data collections are far from being "standardized" so to be harmonized or even integrated, making it impossible to fully exploit the latest machine learning technologies for the analysis of data themselves. Hence, facing this huge flow of biomedical data is a challenging task for researchers and clinicians due to their complexity and high heterogeneity. This is the case of neurodegenerative diseases and the Alzheimer's Disease (AD) in whose context specialized data collections such as the one by the Alzheimer's Disease Neuroimaging Initiative (ADNI) are maintained. METHODS: Ontologies are controlled vocabularies that allow the semantics of data and their relationships in a given domain to be represented. They are often exploited to aid knowledge and data management in healthcare research. Computational Ontologies are the result of the combination of data management systems and traditional ontologies. Our approach is i) to define a computational ontology representing a logic-based formal conceptual model of the ADNI data collection and ii) to provide a means for populating the ontology with the actual data in the Alzheimer Disease Neuroimaging Initiative (ADNI). These two components make it possible to semantically query the ADNI database in order to support data extraction in a more intuitive manner. RESULTS: We developed: i) a detailed computational ontology for clinical multimodal datasets from the ADNI repository in order to simplify the access to these data; ii) a means for populating this ontology with the actual ADNI data. Such computational ontology immediately makes it possible to facilitate complex queries to the ADNI files, obtaining new diagnostic knowledge about Alzheimer's disease. CONCLUSIONS: The proposed ontology will improve the access to the ADNI dataset, allowing queries to extract multivariate datasets to perform multidimensional and longitudinal statistical analyses. Moreover, the proposed ontology can be a candidate for supporting the design and implementation of new information systems for the collection and management of AD data and metadata, and for being a reference point for harmonizing or integrating data residing in different sources.

Genome-wide association identifies the first risk loci for psychosis in Alzheimer disease.

Psychotic symptoms, defined as the occurrence of delusions or hallucinations, are frequent in Alzheimer disease (AD with psychosis, AD + P). AD + P affects ~50% of individuals with AD, identifies a subgroup with poor outcomes, and is associated with a greater degree of cognitive impairment and depressive symptoms, compared to subjects without psychosis (AD - P). Although the estimated heritability of AD + P is 61%, genetic sources of risk are unknown. We report a genome-wide meta-analysis of 12,317 AD subjects, 5445 AD + P. Results showed common genetic variation accounted for a significant portion of heritability. Two loci, one in ENPP6 (rs9994623, O.R. (95%CI) 1.16 (1.10, 1.22), p = 1.26 × 10-8) and one spanning the 3'-UTR of an alternatively spliced transcript of SUMF1 (rs201109606, O.R. 0.65 (0.56-0.76), p = 3.24 × 10-8), had genome-wide significant associations with AD + P. Gene-based analysis identified a significant association with APOE, due to the APOE risk haplotype ε4. AD + P demonstrated negative genetic correlations with cognitive and educational attainment and positive genetic correlation with depressive symptoms. We previously observed a negative genetic correlation with schizophrenia; instead, we now found a stronger negative correlation with the related phenotype of bipolar disorder. Analysis of polygenic risk scores supported this genetic correlation and documented a positive genetic correlation with risk variation for AD, beyond the effect of ε4. We also document a small set of SNPs likely to affect risk for AD + P and AD or schizophrenia. These findings provide the first unbiased identification of the association of psychosis in AD with common genetic variation and provide insights into its genetic architecture.

DMapp: a developing promising approach to monitor symptoms progression and stimulate memory in Italian people with cognitive impairments.

BACKGROUND: Based on recent researches on the use of natural language processing techniques for very early detection of cognitive decline and the benefits of cognitive stimulation for people with cognitive impairments, the Dementia Monitoring application (DMapp) is developed inside the Memento project. AIMS: The aims of this work are: (1) to present DMapp; (2) to report the results of two preliminary studies on DMapp; (3) to describe the clinical and experimental potentiality of DMapp. METHODS: Italian people with the diagnosis of mild cognitive impairment due to Alzheimer's disease or dementia due to Alzheimer's Disease with a Mini-Mental-State-Examination between 24 and 28 (inclusive) were involved in the DMapp development prototype during the Lab Trial (4 subjects) and Filed Trial (5 subjects) of the Memento project. Qualitative and quantitative data were collected to evaluate participants' opinions, the DMapp ability to perform the automatic analysis of the speech and participants' visible emotional state effective. Ad hoc interviews, the Observed Emotion Rating Scale and performance metrics to solve different tasks were used. The relation between cognitive measures (global cognitive measures) and linguistic indexes values was considered using Euclidean distances between the participants. RESULTS: Linguistic indexes were calculated and seemed to classify the participants' performance as expected from cognitive measures. The DMapp was appreciated by people with cognitive impairment. Positive emotions were present. CONCLUSION: DMapp seems an interesting approach to monitor dementia symptoms progression and stimulate memory. Possible developments and open questions are discussed.

Dealing with dehydration in hospitalized oldest persons: accuracy of the calculated serum osmolarity.

BACKGROUND:  Assessment of hydration status is complex and difficult to detect in older persons. Different methods have been developed to determine hydration status in clinical settings, but their diagnostic accuracy remains questionable. AIMS: The aim of this study was to determine and compare the diagnostic accuracy of all methods routinely used in acute settings to detect dehydration in a cohort of hospitalized oldest-old persons, using as primary reference standard blood urea nitrogen (BUN) to creatinine ratio. METHODS:  This retrospective study was conducted on 59 oldest-old subjects at hospital admission in an acute setting, with complete physical, biochemical, bioelectrical impedance analysis (BIA) and ultrasound assessment, including inferior vena cava diameters. RESULTS: Fifty-nine (45 women/14 men) subjects, with a mean age of 87.4 ± 5.9 years, were studied. Based on the value of the BUN/creatinine ratio, the whole population was divided into hyperhydrated (n = 10), normohydrated (n = 42), and dehydrated (n = 7) groups. Among parameters indicating the hydration status, serum sodium levels (p < 0.0001), serum chloride levels (p = 0.010), calculated plasma osmolarity (p < 0.0001), and fat mass (FM) (p = 0.030) differed significantly among groups. A ROC analysis showed that the highest and most significant value for dehydration detection was the calculated plasma osmolarity (AUC: 0.820, p = 0.013), which significantly correlated with clinical parameters including heart rate (r = 0.300; p = 0.021), capillary refill (r = 0.379; p = 0.013) and systolic blood pressure (r = - 0.261; p = 0.046). DISCUSSION: The measurement of calculated serum osmolarity is simple and inexpensive and may quickly provide high sensitivity and specificity indication of dehydration in hospitalized oldest-old persons.

Fighting social isolation in times of pandemic COVID-19: the role of video calls for older hospitalized patients.

BACKGROUND: Loneliness and social isolation are associated with anxiety and psychological discomfort, especially amongst the oldest and fragile persons. AIMS: SILVER evaluates the acceptance of video calls by old hospitalized patients and their relatives during the ban on visits due to the COVID-19. Moreover, SILVER evaluates if the use of different communication technology is associated with different outcomes in terms of anxiety, fear of self and of others' death and mood. METHODS: SILVER is an observational multicentre study. Patients hospitalized in two geriatric units in Switzerland and in one orthogeriatric unit in Italy and their relatives were enrolled. Participants can freely choose to use phone or video calls and were evaluated over a week. We measured anxiety, fear of death and mood at baseline and at the end of the study with standard scales. The use of video or phone calls was associated to a change in these parameters by two-way ANOVA for repeated measures. RESULTS: Sixty-four patients and relatives were enrolled, 26.5% used phone calls and 73.5% video calls. The use of video calls was associated with a reduction in anxiety and fear of death in patients and relatives as compared to participants using phone calls. DISCUSSION: Old patients and their relatives accepted and appreciated the use of video calls during hospitalization; moreover, participant using video calls appears to be less anxious and less afraid of death. CONCLUSIONS: Video calls may be a useful communication tool for hospitalized older patients to keep social relationships with relatives and reduce their anxiety and fear of death. TRIAL REGISTRATION: Retrospectively registered on 1st September 2021 in ClinicalTrials.gov (NCT05000099).

User experience and acceptance of a device assisting persons with dementia in daily life: a multicenter field study.

BACKGROUND: Assistive technologies have the potential to facilitate everyday life of people with dementia and their families. Close collaboration with affected people and interdisciplinary research are essential to understand and address the needs of prospective users. In this study, we present the results of the evaluation of such an assistive system prototype. AIMS: Challenges from the patient and caregiver side, technical and design problems and acceptance and usability with regard to our special target group were evaluated. METHODS: MEMENTO, a system of two e-ink tablets and a smartwatch, was tested in the domestic environment of dementia patients. Thirty participants from Italy, Spain and Austria took part in a 3-month field trial and compared the MEMENTO system to traditional strategies in everyday life. Quantitative and qualitative data were collected and frequency of use of the system was monitored. RESULTS: There were no significant changes in quantitative measurements, such as activities of daily living and caregiver burden over the duration of the 3-month field trial. More frequent usage was significantly correlated with positive attitude towards technology (r = 0.723, p < 0.05), but not with age. The design of the system was positively emphasized, reducing fear of the technology on the one hand and stigmatization on the other. CONCLUSION: We show that a positive attitude towards technology is the essential variable for successful implementation of such systems, regardless of age. Participants showed great interest in digital solutions and agreed that technological systems will help in maintaining independency of persons with cognitive dysfunction in the future.

Alzheimer's disease research progress in the Mediterranean region: The Alzheimer's Association International Conference Satellite Symposium.

As research and services in the Mediterranean region continue to increase, so do opportunities for global collaboration. To support such collaborations, the Alzheimer's Association was due to hold its seventh Alzheimer's Association International Conference Satellite Symposium in Athens, Greece in 2021. Due to the COVID-19 pandemic, the meeting was held virtually, which enabled attendees from around the world to hear about research efforts in Greece and the surrounding Mediterranean countries. Research updates spanned understanding the biology of, treatments for, and care of people with Alzheimer's disease (AD_ and other dementias. Researchers in the Mediterranean region have outlined the local epidemiology of AD and dementia, and have identified regional populations that may expedite genetic studies. Development of biomarkers is expected to aid early and accurate diagnosis. Numerous efforts have been made to develop culturally specific interventions to both reduce risk of dementia, and to improve quality of life for people living with dementia.

Harmonizing neuropsychological assessment for mild neurocognitive disorders in Europe.

INTRODUCTION: Harmonized neuropsychological assessment for neurocognitive disorders, an international priority for valid and reliable diagnostic procedures, has been achieved only in specific countries or research contexts. METHODS: To harmonize the assessment of mild cognitive impairment in Europe, a workshop (Geneva, May 2018) convened stakeholders, methodologists, academic, and non-academic clinicians and experts from European, US, and Australian harmonization initiatives. RESULTS: With formal presentations and thematic working-groups we defined a standard battery consistent with the U.S. Uniform DataSet, version 3, and homogeneous methodology to obtain consistent normative data across tests and languages. Adaptations consist of including two tests specific to typical Alzheimer's disease and behavioral variant frontotemporal dementia. The methodology for harmonized normative data includes consensus definition of cognitively normal controls, classification of confounding factors (age, sex, and education), and calculation of minimum sample sizes. DISCUSSION: This expert consensus allows harmonizing the diagnosis of neurocognitive disorders across European countries and possibly beyond.

Uric acid and late-onset Alzheimer's disease: results from the ReGAl 2.0 project.

BACKGROUND: It has been suggested that oxidative stress may have a role in the pathogenesis of Alzheimer's disease (AD). Serum uric acid (UA) could exert neuroprotective effects via its antioxidant capacities. Many studies investigated serum UA levels in subjects with AD, but to date, results are conflicting and evidence in old age subjects is weak. AIMS: In this study, we assess whether serum UA levels would be altered in the AD old age subjects compared to those of initial cognitive impairment and healthy controls. METHODS: This is a retrospective study with data gathered from the ReGAl 2.0 project (Rete Geriatrica Alzheimer-Geriatric Network on Alzheimer's disease), a large Italian multicentric clinical-based study. A cohort of 232 subjects, including 65 (healthy controls HC), 95 mild cognitive impairment (MCI), and 72 AD, were included in the study. Serum UA was measured in all subjects by routine laboratory method. RESULTS: The sample population includes 232 subjects, mostly women with a mean age of 79.16 ± 5.64 (range 66-93) years. No significant difference was found in gender distribution between groups. No significant correlation was found in all populations between age and uric acid levels. AD group had significantly lower UA levels as compared with HC. The association of uric acid with AD presence after adjusting for age, gender, body mass index (BMI) and creatinine levels showed that uric acid level was independently associated with the diagnosis of AD. CONCLUSIONS: These data indicate that serum UA is reduced in AD, supporting that UA may have a potential protective role against AD in old age.

Serum alkaline phosphatase is elevated and inversely correlated with cognitive functions in subjective cognitive decline: results from the ReGAl 2.0 project.

BACKGROUND: Alkaline phosphatase has been found on neuronal membranes and plasma alkaline phosphatase (ALP) activity increases during brain injury and cerebrovascular diseases, suggesting that its levels may reflect the neuronal loss. It is known that ALP is higher in subjects affected by Alzheimer's dementia and inversely correlated with cognitive functions. No study has investigated the relationship between ALP and cognitive functions in old-age subject with pre-clinical cognitive impairment. METHODS: This is a cross-sectional study with data gathered from the ReGAl 2.0 project (Rete Geriatrica Alzheimer-Geriatric Network on Alzheimer's disease), a large Italian multicentric clinical-based study. A cohort of 209 old-age subjects healthy controls (HC), Subjective cognitive decline (SCD), and Mild Cognitive Impairment (MCI) was included in the study. Cognitive performances were assessed with a large neuropsychological battery. The same day, serum alkaline phosphatase activity was measured in all subjects. RESULTS: We found that the SCD group had significantly higher ALP levels as compared with HC (p = 0.001). Among all neuropsychological tests, in all population ALP levels negatively correlated with scores at attentional matrices (r = - 0.243, p = 0.002), Digit Span Forward (r = - 0.241, p = 0.003) and Letter Fluency Test (r = - 0.196, p = 0.044). Attentional Matrices (r = - 0.208, p = 0.014) and Letter Fluency Test (r = - 0.229, p = 0.019) remained significantly correlated with ALP even after controlling for gender. In the SCD group, only the Attentional Matrices significantly and negatively correlated with ALP (r = - 0.344 p = 0.035), while no significant correlations were found in HC or MCI. CONCLUSIONS: Results indicate that serum alkaline phosphatase activity is increased in SCD and inversely correlates with cognitive functions. Further studies are needed to investigate the role of ALP in the progression to AD.

The diagnostic and prognostic capabilities of plasma biomarkers in Alzheimer's disease.

INTRODUCTION: This study investigated the diagnostic and disease-monitoring potential of plasma biomarkers in mild cognitive impairment (MCI) and Alzheimer's disease (AD) dementia and cognitively unimpaired (CU) individuals. METHODS: Plasma was analyzed using Simoa assays from 99 CU, 107 MCI, and 103 AD dementia participants. RESULTS: Phosphorylated-tau181 (P-tau181), neurofilament light, amyloid-ß (Aß42/40), Total-tau and Glial fibrillary acidic protein were altered in AD dementia but P-tau181 significantly outperformed all biomarkers in differentiating AD dementia from CU (area under the curve [AUC] = 0.91). P-tau181 was increased in MCI converters compared to non-converters. Higher P-tau181 was associated with steeper cognitive decline and gray matter loss in temporal regions. Longitudinal change of P-tau181 was strongly associated with gray matter loss in the full sample and with Aß measures in CU individuals. DISCUSSION: P-tau181 detected AD at MCI and dementia stages and was strongly associated with cognitive decline and gray matter loss. These findings highlight the potential value of plasma P-tau181 as a non-invasive and cost-effective diagnostic and prognostic biomarker in AD.