How long have you exercised in your life? The effect of motor reserve and current physical activity on cognitive performance.

OBJECTIVES: Aging of the population encourages research on how to preserve cognition and quality of life. Many studies have shown that Physical Activity (PA) positively affects cognition in older adults. However, PA carried out throughout the individual's lifespan may also have an impact on cognition in old age. We hypothesize the existence of Motor Reserve (MR), a flexible and dynamic construct that increases over time and compensates for age-related motor and cognitive loss. METHODS: Two questionnaires were developed and validated to estimate MR (Physical Activity carried out throughout the individual's lifespan) and Current Physical Activity (CPA, PA carried out in the previous 12 months). They were administered to 75 healthy individuals over 50 to verify the relation with cognition. MR and CPA include physical exercise (i.e., structured activities to improve or maintain physical fitness) and incidental PA, which we consider as any movement that leads to a metabolic cost above baseline (e.g., housekeeping, walking). In addition, the Cognitive Reserve Index questionnaire (CRI), a reliable predictor of cognitive performance, was used to measure each participant's Cognitive Reserve. RESULTS: The factors that most influenced performance are Age and Cognitive Reserve, but also MR and CPA together and MR when it is the only factor. CONCLUSIONS: Cognitive variability in adult and elderly populations is explained by both MR and CPA. PA training could profitably be included in new preventive and existing interventions.

The Telephone Language Screener (TLS): standardization of a novel telephone-based screening test for language impairment.

BACKGROUND: This study aimed at developing and standardizing the Telephone Language Screener (TLS), a novel, disease-nonspecific, telephone-based screening test for language disorders. METHODS: The TLS was developed in strict pursuance to the current psycholinguistic standards. It comprises nine tasks assessing phonological, lexical-semantic and morpho-syntactic components, as well as an extra Backward Digit Span task. The TLS was administered to 480 healthy participants (HPs), along with the Telephone-based Semantic Verbal Fluency (t-SVF) test and a Telephone-based Composite Language Index (TBCLI), as well as to 37 cerebrovascular/neurodegenerative patients-who also underwent the language subscale of the Telephone Interview for Cognitive Status (TICS-L). An HP subsample was also administered an in-person language battery. Construct validity, factorial structure, internal consistency, test-retest and inter-rater reliability were tested. Norms were derived via Equivalent Scores. The capability of the TLS to discriminate patients from HPs and to identify, among the patient cohort, those with a defective TICS-L, was also examined. RESULTS: The TLS was underpinned by a mono-component structure and converged with the t-SVF (p < .001), the TBCLI (p < .001) and the in-person language battery (p = .002). It was internally consistent (McDonald's ω = 0.67) and reliable between raters (ICC = 0.99) and at retest (ICC = 0.83). Age and education, but not sex, were predictors of TLS scores. The TLS optimally discriminated patients from HPs (AUC = 0.80) and successfully identified patients with an impaired TICS-L (AUC = 0.92). In patients, the TLS converged with TICS-L scores (p = 0.016). DISCUSSION: The TLS is a valid, reliable, normed and clinically feasible telephone-based screener for language impairment.

Over ninety years old: Does high cognitive reserve still help brain efficiency?

Nonagenarians and centenarians, also called oldest-old, are a very heterogeneous population that counts a limited number of individuals as it is a real challenge to reach this goal. Even if it is well known that cognitive reserve can be considered a factor in maintaining good cognitive functioning in ageing, only very few studies have been carried out on the role of cognitive reserve (CR) in the oldest-old people. The aim of this study is to investigate the relationship between cognitive reserve and cognitive functioning in a population living in a specific region of Italy, the Blue Zone in Sardinia. This population is characterised by extreme longevity and distinctive historical, geographic, social, linguistic and nutritional features. The cognitive Reserve Index questionnaire (CRIq) and the short cognitive Esame Neuropsicologico Breve-2 (ENB-2, Brief Neuropsychological Examination) were administered to 67 participants, all aged between 90 and 105 years old. The CRIq was a predictor of neuropsychological performance for the global score of the battery of tests, ENB-2 (ENB-tot) and also for 7 out of 16 of its sub-tests. All except one (Token) tapped executive functions (Interference memory at 10 and 30 s, TMT-B, Overlapping figures, Abstraction, Fluency). Results highlight that also in the oldest-old population CR has a positive effect on cognition, especially on executive functioning.

Cognitive reserve modulates mental health in adulthood.

Cognitive Reserve (CR) reflects acquired knowledge, skills, and abilities throughout life, and it is known for modulating cognitive efficiency in healthy and clinical populations. CR, which was initially proposed to explain individual differences in the clinical presentation of dementia, has subsequently been extended to healthy ageing, showing its role in cognitive efficiency also during middle age. Recently, CR has been linked to affective processes in psychiatric conditions such as schizophrenia, major depressive and anxiety symptoms, and psychological distress, suggesting its potential role in emotional expression and regulation. Whether the role of CR in mental health extends to non-pathological adults, and whether this is only relevant in older age is not yet clear. The aim of this work was therefore to explore the relationship between CR and mental health in healthy adults, with a focus on middle adulthood (40-60). In a sample of 96 participants, we found a positive association between CR and mental health outcomes, such that a higher cognitive reserve index corresponded to fewer mental health reported symptoms. Specifically, a higher CR reflecting professional activities was associated with lower stress levels, especially in middle agers. Taken together, these data therefore suggest that engaging occupations may help maintain a robust mental health, especially by reducing stress symptoms during middle age. These results broaden previous findings suggesting that CR relates to affective components of mental health in middle aged and older adults.

Cognitive reserve proxies for individuals with intellectual developmental disability: A scoping review.

BACKGROUND: Cognitive reserve (CR) has not been studied in people with Intellectual Developmental Disability, a population with a high incidence of dementia. Commonly adopted CR proxies should be adapted to reflect more specifically the experiences of people with Intellectual Developmental Disability. METHOD: This scoping review intended to identify CR proxies relevant to people with this condition. RESULTS: Some of these were the same already detected in a population without intellectual disabilities (education, occupation, physical activity, leisure, community and social activities); others were found to be specifically relevant for this population: type of schooling, parental educational level, environmental stimulation and living place. CONCLUSIONS: These proxies need to be considered in studies on CR and Intellectual Developmental Disability and in clinical practice. Research on the protective effect of CR aims to encourage policies promoting lifestyle-based educational and preventive interventions and overcome participation barriers for people with Intellectual Developmental Disability.

Tele-Global Examination of Mental State (Tele-GEMS): an open tool for the remote neuropsychological screening.

Tele-neuropsychology, i.e., the application of remote audio-visual technologies to neuropsychological evaluation or rehabilitation, has become increasingly popular and widespread during and after the COVID-19 pandemic. New tools with updated normative data and appropriate methodological developments are necessary. We present Tele-GEMS, a telephone-based cognitive screening developed on N = 601 Italian participants. It yields a global score tapping on orientation, memory, spatial representation, language, and pragmatic abilities. Its administration lasts about 10 min. Clinical cut-offs are provided, accounting for demographic variables (age, education, and sex) and also for a comprehensive index taking into account cognitively stimulating life experiences that can build up a cognitive reserve. Tele-GEMS shows good internal consistency and a good inter-rater agreement. The test includes the thresholds for estimating a significant change after repeated measurements. Tele-GEMS has a good construct validity as assessed with MoCA and a suitable criterion validity assessed with its in-person version (GEMS). All the materials and the instructions, including scripts and an online Application for the automatic calculation of cut-offs, are accessible on OSF at https://osf.io/t3bma/ under a Creative Commons license.

s-CRIq: the online short version of the Cognitive Reserve Index Questionnaire.

BACKGROUND: The wide use of the term Cognitive Reserve (CR) is in need of a clear and shared definition of its concept and of the development of new tools, quick and easy to use and updated for the people of today. This study describes the online short CRIq (s-CRIq), the new shorter version of the CRIq, following an item analysis revision, and compares the data distribution of different samples. METHODS: The s-CRIq was administered online to 435 people while another 440 filled out the s-CRIq in self-administration. A further 588 participants had been administered the original paper-and-pencil long CRIq and 344 the online long CRIq. RESULTS: The major difference in the databases of s-CRIq versus the long versions is an increased score in education and in leisure activity. However, the density distributions of the total score of CRI in the 4 databases share 64% of their areas, and at least two of them share 84%. CONCLUSION: The s-CRIq proved to be a simple and easy-to-administer tool. Similarly, to the original version, the s-CRIq is freely available on the web, and it is our hope that it will be of fruitful use for researchers and clinicians alike.

Protective factors for subjective cognitive decline individuals: trajectories and changes in a longitudinal study with Italian elderly.

BACKGROUND AND PURPOSE: Many different factors have been hypothesized to modulate cognition in an aging population according to their functioning at baseline. METHODS: This retrospective study quantifies the relative contribution of age and sex as demographic factors, comorbidity, education and occupation (classified with the International Standard Classification of Occupation 2008) as cognitive reserve proxies in accounting for cognitive aging. All participants (3081) were evaluated at baseline with a complete neuropsychological test battery (T1) and those with unimpaired profiles were classified as subjective cognitive decline, those mildly impaired as mild neurocognitive decline and those severely impaired as major neurocognitive decline. From the first assessment 543 individuals were assessed a second time (T2), and 125 a third time (T3). Depending on whether they maintained or worsened their profile, based on their initial performance, participants were then classified as resistant or declining. RESULTS: At baseline, all individuals showed education and occupation as the best predictors of performance, in addition to age. Furthermore, across assessments, the resistant had higher levels of education and occupation than the declining. In particular, the education and occupation predicted cognitive performance in all groups considered, from the subjective cognitive decline to the one with the most severely impaired participants. CONCLUSIONS: This study highlights the role of working activity in protecting from cognitive decline across all fragile elderly groups and even more so the individuals who are at very high risk of decline.

Italian telephone-based Mini-Mental State Examination (Itel-MMSE): item-level psychometric properties.

BACKGROUND: The Italian telephone-based Mini-Mental State Examination (Itel-MMSE), despite being psychometrically sound, has shown relevant ceiling effects, which may negatively impact the interpretation of its scores. In address to overcome such an issue, this study aimed at providing item-level insights on the Itel-MMSE through Item Response Theory (IRT) analyses. METHODS: Five-hundred and sixty-seven healthy Italian adults (227 males, 340 females; mean age: 51 ± 17 years, range 18-96; mean education: 13.31 ± 4.3 years). A two-parameter logistic IRT model was implemented to assess item discrimination and difficulty of the Itel-MMSE. Construct unidimensionality, statistical independence of items, and model and item fit were tested. Informativity levels were also assessed graphically. RESULTS: With respect to the Itel-MMSE total score, ceiling effects were found in 92.7% of participants. Unidimensionality was violated; both model and item fit were poor; a few items showed statistical dependence. Both the whole test and its items proved to be scarcely informative, especially for medium-to-high levels of ability, except for attention and spatial orientation subtests, which consistently yielded the highest discriminative capability. DISCUSSION: The Itel-MMSE appears to be most informative in low-performing healthy individuals. However, the present findings should not lead practitioners to aprioristically equate ceiling effects/low informativity to clinical uselessness. Items assessing attention and, to a lesser extent, spatial orientation appear to be the most informative.

Telephone-based Frontal Assessment Battery (t-FAB): standardization for the Italian population and clinical usability in neurological diseases.

BACKGROUND: Despite the relevance of telephone-based cognitive screening tests in clinical practice and research, no specific test assessing executive functioning is available. The present study aimed at standardizing and providing evidence of clinical usability for the Italian telephone-based Frontal Assessment Battery (t-FAB). METHODS: The t-FAB (ranging 0-12), comprising two subtests, has two versions: one requiring motor responses (t-FAB-M) and the other verbal responses (t-FAB-V). Three hundred and forty-six Italian healthy adults (HPs; 143 males; age range = 18-96 years; education range = 4-23 years) and 40 participants with neurological diseases were recruited. To HPs, the t-FAB was administered along with a set of telephone-based tests: MMSE, verbal fluency (VF), backward digit span (BDS). The in-person version of the FAB was administered to both HPs and clinical groups. Factorial structure, construct validity, inter-rater and test-retest reliability, t-FAB-M vs. t-FAB-V equivalence and diagnostic accuracy were assessed. Norms were derived via Equivalent Scores. RESULTS: In HPs, t-FAB measures yielded high inter-rater/test-retest reliability (ICC = .78-.94), were internally related (p ≤ .005) and underpinned by a single component, converging with the telephone-based MMSE, VF, BDS (p ≤ .0013). The two t-FAB versions were statistically equivalent in clinical groups (ps of both equivalence bounds < .001). Education predicted all t-FAB scores (p < .001), whereas age only the t-FAB-M score (p ≤ .004). t-FAB scores converge with the in-person FAB in HPs and clinical groups (rs = .43-.78). Both t-FAB versions were accurate in discriminating HPs from the clinical cohort (AUC = .73-.76). DISCUSSION: The t-FAB is a normed, valid, reliable and clinically usable telephone-based cognitive screening test to adopt in both clinical and research practice.

Past Life Experiences and Neurological Recovery: The Role of Cognitive Reserve in the Rehabilitation of Severe Post-Anoxic Encephalopathy and Traumatic Brain Injury.

OBJECTIVE: Patients with an equivalent clinical background may show unexpected interindividual differences in their outcome. The cognitive reserve (CR) model has been proposed to account for such discrepancies, but its role after acquired severe injuries is still being debated. We hypothesize that inappropriate investigative methods might have been used when dealing with severe patients, which have very likely reduced the possibility of observing meaningful influences in recovery from severe traumas. METHODS: To overcome this issue, the potential neuroprotective role of CR was investigated, considering a wider spectrum of clinical symptoms ranging from low-level brain stem functions necessary for life to more complex motor and cognitive skills. In the present study, data from 50 severe patients, 20 suffering from post-anoxic encephalopathy (PAE) and 30 with traumatic brain injury (TBI), were collected and retrospectively analyzed. RESULTS: We found that CR, diagnosis, time of hospitalization, and their interaction had an effect on the clinical indexes. When the predictive power of CR was investigated by means of two machine learning classifier algorithms, CR, together with age, emerged as the strongest factor in discriminating between patients who reached or did not reach successful recovery. CONCLUSIONS: Overall, the present study highlights a possible role of CR in shaping the recovery of severe patients suffering from either PAE or TBI. The practical implications underlying the need to routinely considered CR in the clinical practice are discussed.

Alzheimer Café: an approach focused on Alzheimer's patients but with remarkable values on the quality of life of their caregivers.

BACKGROUND: Alzheimer's disease (AD) affects the global quality of life of persons who suffer from it and their caregivers, because of the behavioral and psychological consequences associated with the pathology and its caring. The Alzheimer Café (AC) is one example of approach aimed to help persons and caregivers deal with their disease. AIM: This is a pilot study focusing on the efficacy of AC in relieving caregivers' and persons' burdens due to dementia. METHODS: The quality of life of both caregivers and persons who attended the AC was compared with the quality of life of those who did not. Basic and instrumental daily activities and neuropsychiatric functioning were assessed. Caregivers also answered to general well-being and caregiving burden questionnaires. The evaluation took place at the beginning of the intervention and after 1, 3, 6, 9 and 12 months. RESULTS: Caregivers who joined the AC with their persons with dementia showed to have significantly benefited in the daily care of persons with dementia, in terms of total well-being, vitality, and emotional burden. DISCUSSION: Although improvements were not observed in persons with dementia who attended the AC, significant benefits were reported by their caregivers, suggesting that the intervention may produce better management of social and economic problems and lead to better emotional support. CONCLUSIONS: The AC seems to help families of AD persons to better manage the disease, and also delay the institutionalization of these persons, which is certainly an ambitious goal for an incurable disorder such as Alzheimer's disease.

Cognitive and motor reaction times in obstructive sleep apnea syndrome: A study based on computerized measures.

Obstructive Sleep Apnea Syndrome (OSAS) is mainly associated with executive dysfunction. Although delayed reaction times (RTs) in patients with OSAS have been reported, sensitivity of processing speed has not been adequately assessed. This study suggests sensitive and reliable measures to clarify whether different components of information processing speed, i.e. cognitive and motor responses, are equally impaired in OSAS. Thirty-three patients with OSAS were compared with thirty healthy controls. The MoCA test was administered to assess participants' global neuropsychological profile. Cognitive and motor reaction times were measured using a detector panel which allows to distinguish between stimulus encoding, decision processing, and selection of the appropriate motor response. Logistic regression models highlighted both MoCA test and motor RTs as the best predictors differentiating patients from healthy participants. Results support the hypothesis of a slight decline in the cognitive profile of patients with OSAS and identify significant slowing down in the motor component of responses. It could be hypothesized that slower motor responsiveness is the cause of the global cognitive profile of these patients. With aging, motor movements and RTs usually become impaired and hypoxia might accelerate the aging process by compromising first of all the motor component of RTs.

Synthesis of Water Dispersible and Catalytically Active Gold-Decorated Cobalt Ferrite Nanoparticles.

Hetero-nanoparticles represent an important family of composite nanomaterials that in the past years are attracting ever-growing interest. Here, we report a new strategy for the synthesis of water dispersible cobalt ferrite nanoparticles (CoxFe3-xO4 NPs) decorated with ultrasmall (2-3 nm) gold nanoparticles (Au NPs). The synthetic procedure is based on the use of 2,3-meso-dimercaptosuccinic acid (DMSA), which plays a double role. First, it transfers cobalt ferrite NPs from the organic phase to aqueous media. Second, the DMSA reductive power promotes the in situ nucleation of gold NPs in proximity of the magnetic NP surface. Following this procedure, we achieved a water dispersible nanosystem (CoxFe3-xO4-DMSA-Au NPs) which combines the cobalt ferrite magnetic properties with the catalytic features of ultrasmall Au NPs. We showed that CoxFe3-xO4-DMSA-Au NPs act as an efficient nanocatalyst to reduce 4-nitrophenol to 4-aminophenol and that they can be magnetically recovered and recycled. It is noteworthy that such nanosystem is more catalytically active than Au NPs with equal size. Finally, a complete structural and chemical characterization of the hetero-NPs is provided.

Human memory retrieval and inhibitory control in the brain: beyond correlational evidence.

Retrieving information from long-term memory can result in the episodic forgetting of related material. One influential account states that this retrieval-induced forgetting (RIF) phenomenon reflects inhibitory mechanisms called into play to decrease retrieval competition. Recent neuroimaging studies suggested that the prefrontal cortex, which is critically engaged in inhibitory processing, is also involved in retrieval competition situations. Here, we used transcranial direct current stimulation (tDCS) to address whether inhibitory processes could be causally linked to RIF. tDCS was administered over the right dorsolateral prefrontal cortex during the retrieval-practice phase in a standard retrieval-practice paradigm. Sixty human participants were randomly assigned to anodal, cathodal, or sham-control groups. The groups showed comparable benefits for practiced items. In contrast, unlike both the sham and anodal groups, the cathodal group exhibited no RIF. This pattern is interpreted as evidence for a causal role of inhibitory mechanisms in episodic retrieval and forgetting.

Zwitterion-Coated Iron Oxide Nanoparticles: Surface Chemistry and Intracellular Uptake by Hepatocarcinoma (HepG2) Cells.

Nanoparticles (NPs) have received much attention in recent years for their diverse potential biomedical applications. However, the synthesis of NPs with desired biodistribution and pharmacokinetics is still a major challenge, with NP size and surface chemistry being the main factors determining the behavior of NPs in vivo. Here we report on the surface chemistry and in vitro cellular uptake of magnetic iron oxide NPs coated with zwitterionic dopamine sulfonate (ZDS). ZDS-coated NPs were compared to similar iron oxide NPs coated with PEG-like 2-[2-(2-methoxyethoxy)ethoxy]acetic acid (MEEA) to investigate how surface chemistry affects their in vitro behavior. ZDS-coated NPs had a very dense coating, guaranteeing high colloidal stability in several aqueous media and negligible interaction with proteins. Treatment of HepG2 cells with increasing doses (2.5-100 µg Fe/mL) of ZDS-coated iron oxide NPs had no effect on cell viability and resulted in a low, dose-dependent NP uptake, inferior than most reported data for the internalization of iron oxide NPs by HepG2 cells. MEEA-coated NPs were scarcely stable and formed micrometer-sized aggregates in aqueous media. They decreased cell viability for dose ≥50 µg Fe/mL, and were more efficiently internalized than ZDS-coated NPs. In conclusion, our data indicate that the ZDS layer prevented both aggregation and sedimentation of iron oxide NPs and formed a biocompatible coating that did not display any biocorona effect. The very low cellular uptake of ZDS-coated iron NPs can be useful to achieve highly selective targeting upon specific functionalization.

Assessing the effects of tDCS over a delayed response inhibition task by targeting the right inferior frontal gyrus and right dorsolateral prefrontal cortex.

Many situations in our everyday life call for a mechanism deputed to outright stop an ongoing course of action. This behavioral inhibition ability, known as response stopping, is often impaired in psychiatric conditions characterized by impulsivity and poor inhibitory control. Transcranial direct current stimulation (tDCS) has recently been proposed as a tool for modulating response stopping in such clinical populations, and previous studies in healthy humans have already shown that this noninvasive brain stimulation technique is effectively able to improve response stopping, as measured in a stop-signal task (SST) administered immediately after the stimulation. So far, the right inferior frontal gyrus (rIFG) has been the main focus of these attempts to modulate response stopping by the means of noninvasive brain stimulation. However, other cortical areas such as the right dorsolateral prefrontal cortex (rDLPFC) have been implicated in inhibitory control with other paradigms. In order to provide new insight about the involvement of these areas in response stopping, in the present study, tDCS was delivered to 115 healthy subjects, using five stimulation setups that differed in terms of target area (rIFG or rDLPFC) and polarity of stimulation (anodal, cathodal, or sham). The SST was performed 15 min after the offset of the stimulation. Consistently with previous studies, only anodal stimulation over rIFG induced a reliable, although weak, improvement in the SST, which was specific for response stopping, as it was not mirrored in more general reaction time measures.

Transcranial direct current stimulation and cognitive training in the rehabilitation of Alzheimer disease: A case study.

In the present study we tested the cognitive effects of transcranial direct current stimulation (tDCS) in a case of probable Alzheimer disease (AD). The patient (male, 60 years, mild AD) underwent two cycles of treatments, separated by 2 months. In the first cycle, active stimulation (10 sessions, 2 mA for 20 min; anode over the left dorsolateral prefrontal cortex) was followed by computerised tasks (CTs) specifically chosen to engage the most impaired cognitive processes in the patient (tDCS+CT condition). In the second cycle, which was structured as the first, CTs were administered after placebo stimulation (sham+CT condition). Effects on cognitive performance were evaluated not only by the CTs, but also by neuropsychological tests assessing global cognitive functioning. Statistical analyses revealed that whereas the tDCS+CT condition had few effects on the CTs, it induced a stability of the patient's global cognitive functioning lasting approximately 3 months, which was not achieved when the patient underwent sham+CT condition. Therefore, the synergetic use of tDCS and CTs appeared to slow down the cognitive decline of our patient. This preliminary result, although in need of further confirmation, suggests the potentiality of tDCS as an adjuvant tool for cognitive rehabilitation in AD.