Biomarkers of aging in frailty and age-associated disorders: State of the art and future perspective

According to the Geroscience concept that organismal aging and age-associated diseases share the same basic molecular mechanisms, the identification of biomarkers of age that can efficiently classify people as biologically older (or younger) than their chronological (i.e. calendar) age is becoming of paramount importance. These people will be in fact at higher (or lower) risk for many different age-associated diseases, including cardiovascular diseases, neurodegeneration, cancer, etc. In turn, patients suffering from these diseases are biologically older than healthy age-matched individuals. Many biomarkers that correlate with age have been described so far. The aim of the present review is to discuss the usefulness of some of these biomarkers (especially soluble, circulating ones) in order to identify frail patients, possibly before the appearance of clinical symptoms, as well as patients at risk for age-associated diseases. An overview of selected biomarkers will be discussed in this regard, in particular we will focus on biomarkers related to metabolic stress response, inflammation, and cell death (in particular in neurodegeneration), all phenomena connected to inflammaging (chronic, low-grade, age-associated inflammation). In the second part of the review, next-generation markers such as extracellular vesicles and their cargos, epigenetic markers and gut microbiota composition, will be discussed. Since recent progresses in omics techniques have allowed an exponential increase in the production of laboratory data also in the field of biomarkers of age, making it difficult to extract biological meaning from the huge mass of available data, Artificial Intelligence (AI) approaches will be discussed as an increasingly important strategy for extracting knowledge from raw data and providing practitioners with actionable information to treat patients

Development and Validation of Automated Magnetic Resonance Parkinsonism Index 2.0 to Distinguish Progressive Supranuclear Palsy-Parkinsonism From Parkinson's Disease

Background: Differentiating progressive supranuclear palsy-parkinsonism (PSP-P) from Parkinson's disease (PD) is clinically challenging. Objective: This study aimed to develop an automated Magnetic Resonance Parkinsonism Index 2.0 (MRPI 2.0) algorithm to distinguish PSP-P from PD and to validate its diagnostic performance in two large independent cohorts. Methods: We enrolled 676 participants: a training cohort (n = 346; 43 PSP-P, 194 PD, and 109 control subjects) from our center and an independent testing cohort (n = 330; 62 PSP-P, 171 PD, and 97 control subjects) from an international research group. We developed a new in-house algorithm for MRPI 2.0 calculation and assessed its performance in distinguishing PSP-P from PD and control subjects in both cohorts using receiver operating characteristic curves. Results: The automated MRPI 2.0 showed excellent performance in differentiating patients with PSP-P from patients with PD and control subjects both in the training cohort (area under the receiver operating characteristic curve [AUC] = 0.93 [95% confidence interval, 0.89–0.98] and AUC = 0.97 [0.93–1.00], respectively) and in the international testing cohort (PSP-P versus PD, AUC = 0.92 [0.87–0.97]; PSP-P versus controls, AUC = 0.94 [0.90–0.98]), suggesting the generalizability of the results. The automated MRPI 2.0 also accurately distinguished between PSP-P and PD in the early stage of the diseases (AUC = 0.91 [0.84–0.97]). A strong correlation (r = 0.91, P < 0.001) was found between automated and manual MRPI 2.0 values. Conclusions: Our study provides an automated, validated, and generalizable magnetic resonance biomarker to distinguish PSP-P from PD. The use of the automated MRPI 2.0 algorithm rather than manual measurements could be important to standardize measures in patients with PSP-P across centers, with a positive impact on multicenter studies and clinical trials involving patients from different geographic regions. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Cognitive and mental health changes and their vulnerability factors related to COVID-19 lockdown in Italy

The COVID-19 pandemic and government imposed social restrictions like lockdown exposed most individuals to an unprecedented stress, increasing mental health disorders worldwide. We explored subjective cognitive functioning and mental health changes and their possible interplay related to COVID-19-lockdown. We also investigated potential risk factors to identify more vulnerable groups. Across Italy, 1215 respondents completed our Qualtrics-based online-survey during the end of a seven to 10-week imposed lockdown and home confinement (from April 29 to May 17, 2020). We found subjective cognitive functioning and mental health severely changed in association with the lockdown. Under government regulations, cognitive complaints were mostly perceived in routine tasks involving attention, temporal orientation and executive functions\u2014with no changes in language abilities. A paradoxical effect was observed for memory, with reduced forgetfulness compared to pre-lockdown. We found higher severity and prevalence of depression, anxiety disorders, abnormal sleep, appetite changes, reduced libido and health anxiety: with mild-to-severe depression and anxiety prevalence climbing to 32 and 36 percent, respectively, under restrictions. Being female, under 45 years, working from home or being underemployed were all identified as relevant risk factors for worsening cognition and mental health. Frequent consumers of COVID-19 mass media information or residents in highly infected communities reported higher depression and anxiety symptoms, particularly hypochondria in the latter. If similar restrictions are reimposed, governments must carefully consider these more vulnerable groups in their decisions, whilst developing effective global and long-term responses to the cognitive and mental health challenges of this type of pandemic; as well as implementing appropriate psychological interventions with specific guidelines: particularly regarding exposure to COVID-19 mass-media reports

Do old errors always lead to new truths? A randomized controlled trial of errorless goal management training in brain-injured patients

Item does not contain fulltextBoth errorless learning (EL) and Goal Management Training (GMT) have been shown effective cognitive rehabilitation methods aimed at optimizing the performance on everyday skills after brain injury. We examine whether a combination of EL and GMT is superior to traditional GMT for training complex daily tasks in brain-injured patients with executive dysfunction. This was an assessor-blinded randomized controlled trial conducted in 67 patients with executive impairments due to brain injury of non-progressive nature (minimal post-onset time: 3 months), referred for outpatient rehabilitation. Individually selected everyday tasks were trained using 8 sessions of an experimental combination of EL and GMT or via conventional GMT, which follows a trial-and-error approach. Primary outcome measure was everyday task performance assessed after treatment compared to baseline. Goal attainment scaling, rated by both trainers and patients, was used as secondary outcome measure. EL-GMT improved everyday task performance significantly more than conventional GMT (adjusted difference 15.43, 95% confidence interval [CI] [4.52, 26.35]; Cohen's d=0.74). Goal attainment, as scored by the trainers, was significantly higher after EL-GMT compared to conventional GMT (mean difference 7.34, 95% CI [2.99, 11.68]; Cohen's d=0.87). The patients' goal attainment scores did not differ between the two treatment arms (mean difference 3.51, 95% CI [-1.41, 8.44]). Our study is the first to show that preventing the occurrence of errors during executive strategy training enhances the acquisition of everyday activities. A combined EL-GMT intervention is a valuable contribution to cognitive rehabilitation in clinical practice. (JINS, 2015, 21, 639-649).11 p

Profile and progression of cognitive deficits in Progressive Supranuclear Palsy, Multiple System Atrophy and Parkinson's Disease

Objective: This study investigated neuropsychological tests most sensitive in differentiating progressive supranuclear palsy (PSP) from Parkinson’s disease (PD) and multiple system atrophy (MSA), and in detecting cognitive changes at follow-up. Background: Cognitive impairment is frequent in PSP, but its characteristics and progression need to be properly defined. Method: We evaluated 35 PSP with Richardson’s syndrome (PSP-RS), 30 MSA as well as 65 age-, sex-, and education-matched PD with an extensive clinical and neuropsychological assessment, allowing Level II cognitive diagnosis. Eighteen PSP, 12 MSA and 30 PD had a second evaluation 12-18-month (mean 15 months) after the first assessment. Results: In PSP, Montreal Cognitive Assessment (MoCA), verbal fluencies (phonemic and semantic tasks), Stroop test, Digit Span Sequencing (DSS), incomplete letters of Visual Object and Space Perception (VOSP) and Benton’s Judgment of Line Orientation (JLO) performance were significantly impaired at baseline compared to PD and MSA. Executive and visuo-spatial abilities declined longitudinally in PSP, but not in PD and MSA. After 1.5 year, 16% of PSP converted to dementia. Conclusion: Our study provides evidence that cognitive decline is more severe and rapid in PSP than PD and MSA. MoCA, verbal fluency, DSS and Benton’s JLO are valuable tests to detect cognitive progression in PSP and may be proposed as biomarker for research protocols to assess efficacy of disease modification strategies

Differences in cognitive profiles between Lewy body and Parkinson\u2019s disease dementia

Dementia with Lewy bodies (DLB) and Parkinson\u2019s disease dementia (PDD) not only differ for the time of onset of cognitive deficits but also present variability in affected functions which are relevant in understanding underlying pathology. Cognitive performance of two global cognitive screening scales, the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA), as well as of a neuropsychological test battery, was evaluated in 18 DLB and 21 PDD patients. Feasibility for each cognitive test was investigated. Both MMSE and MoCA are feasible assessments in PDD and DLB patients. MoCA was more sensitive in discriminating groups as higher number of DLB patients showed pathological performances on the Digit Span Forward subitem (p = 0.049). The Stroop test in PDD and the Trail Making Tests\u2014A and B, and the Benton\u2019s judgment of line orientation tests in both groups were considered not feasible. Among feasible cognitive tests in at least one group, Rey\u2013Osterrieth complex figure test copy (p = 0.013) and semantic fluency (p = 0.038) are sensitive in discriminating DLB from PDD cognitive profile. Trail Making Tests\u2014A and B, the Benton\u2019s judgment of line orientation and the Stroop tests are not feasible for assessing patients with frank dementia. Longitudinal studies should not include those tasks to reduce the risk of missing data once disease progresses and dementia develops. DLB patients present more severe and widespread cognitive dysfunction than PDD, particularly in attentive, visuospatial, and language domains