Clinical Profiles in Multiple Sclerosis: Cognitive Reserve and Motor Impairment along Disease Duration.

(i) Background: Cognitive impairment in people with multiple sclerosis (MS) has been studied in relation to certain clinical variables (e.g., motor disability and disease duration) and lifestyle factors such as cognitive reserve (CR). However, only very few studies have considered the interaction of clinical variables and cognitive reserve in preserving the integrity of the neuropsychological profile. In this paper, we hypothesised that a higher level of CR might predict good cognitive efficiency by modulating the clinical outcome of the disease. (ii) Methods: A sample of 100 participants with MS (age range 30-74), was recruited and assessed remotely with a questionnaire to measure CR and a cognitive screening test. Data were analysed through generalized additive models. (iii) Results: We found that the model analysing the interaction between CR and disease duration, and between CR and motor disability, was able to explain a significant percentage of cognitive performance. In particular, higher levels of CR predicted a better cognitive performance despite a long disease duration, unless the motor disability was severe. (iv) Conclusion: This study highlights the crucial role of CR in modulating cognitive efficiency in people with MS.

Education differentiates cognitive performance and resting state fMRI connectivity in healthy aging.

Objectives: In healthy aging, the way people cope differently with cognitive and neural decline is influenced by exposure to cognitively enriching life-experiences. Education is one of them, so that in general, the higher the education, the better the expected cognitive performance in aging. At the neural level, it is not clear yet how education can differentiate resting state functional connectivity profiles and their cognitive underpinnings. Thus, with this study, we aimed to investigate whether the variable education allowed for a finer description of age-related differences in cognition and resting state FC. Methods: We analyzed in 197 healthy individuals (137 young adults aged 20-35 and 60 older adults aged 55-80 from the publicly available LEMON database), a pool of cognitive and neural variables, derived from magnetic resonance imaging, in relation to education. Firstly, we assessed age-related differences, by comparing young and older adults. Then, we investigated the possible role of education in outlining such differences, by splitting the group of older adults based on their education. Results: In terms of cognitive performance, older adults with higher education and young adults were comparable in language and executive functions. Interestingly, they had a wider vocabulary compared to young adults and older adults with lower education. Concerning functional connectivity, the results showed significant age- and education-related differences within three networks: the Visual-Medial, the Dorsal Attentional, and the Default Mode network (DMN). For the DMN, we also found a relationship with memory performance, which strengthen the evidence that this network has a specific role in linking cognitive maintenance and FC at rest in healthy aging. Discussion: Our study revealed that education contributes to differentiating cognitive and neural profiles in healthy older adults. Also, the DMN could be a key network in this context, as it may reflect some compensatory mechanisms relative to memory capacities in older adults with higher education.

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.

State-dependent tDCS modulation of the somatomotor network: A MEG study.

OBJECTIVE: Transcranial direct current stimulation (tDCS) is a non-invasive technique widely used to investigate brain excitability and activity. However, the variability in both brain and behavioral responses to tDCS limits its application for clinical purposes. This study aims to shed light on state-dependency, a phenomenon that contributes to the variability of tDCS. METHODS: To this aim, we investigated changes in spectral activity and functional connectivity in somatomotor regions after Real and Sham tDCS using generalized additive mixed models (GAMMs), which allowed us to investigate how modulation depends on the initial state of the brain. RESULTS: Results showed that changes in spectral activity, but not connectivity, in the somatomotor regions depend on the initial state of the brain, confirming state-dependent effects. Specifically, we found a non-linear interaction between stimulation conditions (Real vs Sham) and initial state: a reduction of alpha and beta power was observed only in participants that had higher alpha and beta power before Real tDCS. CONCLUSIONS: This study highlights the importance of considering state-dependency to tDCS and shows how it can be taken into account with appropriate statistical models. SIGNIFICANCE: Our findings bear insight into tDCS mechanisms, potentially leading to discriminate between tDCS responders and non-responders.

Psychometrics, diagnostics and usability of Italian tools assessing behavioural and functional outcomes in neurological, geriatric and psychiatric disorders: a systematic review.

BACKGROUND: Psychometric instruments assessing behavioural and functional outcomes (BFIs) in neurological, geriatric and psychiatric populations are relevant towards diagnostics, prognosis and intervention. However, BFIs often happen not to meet methodological-statistical standards, thus lowering their level of recommendation in clinical practice and research. This work thus aimed at (1) providing an up-to-date compendium on psychometrics, diagnostics and usability of available Italian BFIs and (2) delivering evidence-based information on their level of recommendation. METHODS: This review was pre-registered (PROSPERO ID: CRD42021295430) and performed according to PRISMA guidelines. Several psychometric, diagnostic and usability measures were addressed as outcomes. Quality assessment was performed via an ad hoc checklist, the Behavioural and Functional Instrument Quality Assessment. RESULTS: Out of an initial N = 830 reports, 108 studies were included (N = 102 BFIs). Target constructs included behavioural/psychiatric symptoms, quality of life and physical functioning. BFIs were either self- or caregiver-/clinician-report. Studies in clinical conditions (including neurological, psychiatric and geriatric ones) were the most represented. Validity was investigated for 85 and reliability for 80 BFIs, respectively. Criterion and factorial validity testing were infrequent, whereas content and ecological validity and parallel forms were almost never addressed. Item response theory analyses were seldom carried out. Diagnostics and norms lacked for about one-third of BFIs. Information on administration time, ease of use and ceiling/floor effects were often unreported. DISCUSSION: Several available BFIs for the Italian population do not meet adequate statistical-methodological standards, this prompting a greater care from researchers involved in their development.

Global Examination of Mental State: An open tool for the brief evaluation of cognition.

BACKGROUND: The aim of this paper is to present a freely accessible new instrument for the evaluation of cognition: the Global Examination of Mental State (GEMS). METHODS: It is made up of 11 items tapping into a range of skills, such as Orientation in time and space, Memory, Working memory, Visuo-spatial, Visuo-constructional and Planning abilities, Perceptual and visual Attention, Language (Naming, Comprehension, and Verbal fluency), and Pragmatics. RESULTS: The psychometric strengths of this screening are: (1) extensive and updated normative data on the adult Italian population (from 18 to 100 years old); (2) absence of ceiling effect in healthy individuals, which allows to better detect interindividual variability; (3) comparison of the global scores with normative data taking into account Cognitive Reserve rather than only education, thus increasing diagnostic accuracy; (4) thresholds for significant change over time and the possibility to use parallel versions (GEMS-A/GEMS-B) for test-retest; (5) solid psychometric properties and data on discriminant validity; and (6) free access to all materials (record forms, instructions, and cut-off scores) on the web under a Creative Common License. CONCLUSIONS: With all these characteristics, GEMS could be a very useful paper-and-pencil instrument for cognitive screening.

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.

Heterogeneity of effects of cognitive reserve on performance in probable Alzheimer's disease and in subjective cognitive decline.

OBJECTIVE: Cognitive reserve (CR) is a term used to describe the adaptability of cognitive processes to brain changes. It helps to explain the different cognitive adaptation to daily functioning in aging individuals and in individuals with brain pathology: a higher CR is associated with a delay in the manifestation of cognitive symptoms. CR is estimated using different proxies, such as education, cognitively stimulating life experiences, premorbid intelligence quotient (IQ), and vocabulary size. Despite the complexity of CR, little research to date has systematically focused on the heterogeneity of its effects. METHOD: We investigated this issue in individuals with probable Alzheimer's Disease (AD) and in individuals with subjective cognitive decline (SCD) by focusing on two variables: (a) the type of CR proxy (i.e., Education and Life experience) and (b) the type of test used to assess cognitive performance (i.e., the Mini-Mental State Examination [MMSE] screening test and the extensive Brief Neuropsychological Examination-2 [ENB-2] test battery). RESULTS: Our results suggest that effects on CR varied: in individuals with probable AD, we found a positive relationship of Education with performance on both the MMSE and the ENB-2 tests; in contrast, individuals with SCD showed a positive relationship of a Life experience proxy selectively with the ENB-2 global score. CONCLUSIONS: Different proxies may reflect different compensatory mechanisms of CR depending on task demand and on an individual's global cognitive condition. In particular, while the Education proxy can capture CR-related cognitive compensation in a pathological condition such as probable AD, the more complex Life experience proxy might be useful for capturing CR-related effects when signs of deterioration are subtle, like in SCD. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Heterogeneity and Factorial Structure in Alzheimer's Disease: A Cognitive Perspective.

BACKGROUND: Alzheimer's disease (AD) patients show heterogeneous cognitive profiles which suggest the existence of cognitive subgroups. A deeper comprehension of this heterogeneity could contribute to move toward a precision medicine perspective. OBJECTIVE: In this study, we aimed 1) to investigate AD cognitive heterogeneity as a product of the combination of within- (factors) and between-patients (sub-phenotypes) components, and 2) to promote its assessment in clinical practice by defining a small set of critical tests for this purpose. METHODS: We performed factor mixture analysis (FMA) on neurocognitive assessment results of N = 230 patients with a clinical diagnosis of AD. This technique allowed to investigate the structure of cognitive heterogeneity in this sample and to characterize the core features of cognitive sub-phenotypes. Subsequently, we performed a tests selection based on logistic regression to highlight the best tests to detect AD patients in our sample. Finally, the accuracy of the same tests in the discrimination of sub-phenotypes was evaluated. RESULTS: FMA revealed a structure characterized by five latent factors and four groups, which were identifiable by means of a few cognitive tests and were mainly characterized by memory deficits with visuospatial difficulties ("Visuospatial AD"), typical AD cognitive pattern ("Typical AD"), less impaired memory ("Mild AD"), and language/praxis deficits with relatively spared memory ("Nonamnestic AD"). CONCLUSION: The structure of cognitive heterogeneity in our sample of AD patients, as studied by FMA, could be summarized by four sub-phenotypes with distinct cognitive characteristics easily identifiable in clinical practice. Clinical implications under the precision medicine framework are discussed.

Corrigendum: Pragmatic Language Disorder in Parkinson's Disease and the Potential Effect of Cognitive Reserve.

[This corrects the article DOI: 10.3389/fpsyg.2019.01220.].

Pragmatic Language Disorder in Parkinson's Disease and the Potential Effect of Cognitive Reserve.

It is known that patients with Parkinson's Disease (PD) may show deficits in several areas of cognition, including speech and language abilities. One domain of particular interest is pragmatics, which refers to the capacity of using language in context for a successful communication. Several studies showed that some specific aspects of pragmatics - both in production and in comprehension - might be impaired in patients with PD. However, a clear picture of pragmatic abilities in PD is still missing, as most of the existing studies focused on specific aspects of the pragmatic competence rather than on sketching a complete pragmatic profile. Moreover, little is known on the potential role of protective factors in compensating the decline of communicative skills as the disease progresses. The present study has two aims: (1) to provide a complete picture of pragmatic abilities in patients with PD, by using a comprehensive battery (Assessment of Pragmatic Abilities and Cognitive Substrates, APACS) and by investigating the relationship with other aspects of cognitive functioning (e.g., working memory and Theory of Mind) and (2) to investigate whether Cognitive Reserve, i.e., the resilience to cognitive impairment provided by life experiences and activities, may compensate for the progressive pragmatic deficits in PD. We found that patients with PD, compared to healthy matched controls, had worse performance in discourse production and in the description of scenes, and that these impairments were tightly correlated with the severity of motor impairment, suggesting reduced intentionality of engaging in a communicative exchange. Patients with PD showed also an impairment in comprehending texts and humor, suggesting a problem in inferring from stories, which was related to general cognitive impairment. Notably, we did not find any significant difference between patients and controls in figurative language comprehension, a domain that is commonly impaired in other neurodegenerative diseases. This might be indicative of a specific profile of pragmatic impairment in patients with PD, worth of further investigation. Finally, Cognitive Reserve measures showed a high degree of association with pragmatic comprehension abilities, suggesting that the modification of life-styles could be a good candidate for compensating the possible problems in understanding the pragmatic aspects of language experienced by patients with PD.

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.

Obstructive sleep apnea and its controversial effects on cognition.

Obstructive sleep apnea syndrome is a sleep disorder that may affect many brain functions. We are interested in the cognitive consequences of the condition with regard to the quality of life of individuals with this disorder. A debate is still underway as to whether cognitive difficulties caused by obstructive sleep apnea actually induce a "pseudodementia" pattern. This work provides a brief overview of the main controversies currently surrounding this issue. We report findings and opinions on structural and cognitive brain changes in individuals affected by obstructive sleep apnea by highlighting the involvement of executive functions and the possible reversibility of signs following-treatment with continuous positive airway pressure. Much research has been done on this issue but, to the best of our knowledge, a review of the present state of the literature evaluating different points of view has not yet been carried out.

Perceptual learning leads to long lasting visual improvement in patients with central vision loss.

BACKGROUND: Macular Degeneration (MD), a visual disease that produces central vision loss, is one of the main causes of visual disability in western countries. Patients with MD are forced to use a peripheral retinal locus (PRL) as a substitute of the fovea. However, the poor sensitivity of this region renders basic everyday tasks very hard for MD patients. OBJECTIVE: We investigated whether perceptual learning (PL) with lateral masking in the PRL of MD patients, improved their residual visual functions. METHOD: Observers were trained with two distinct contrast detection tasks: (i) a Yes/No task with no feedback (MD: N = 3; controls: N = 3), and (ii) a temporal two-alternative forced choice task with feedback on incorrect trials (i.e., temporal-2AFC; MD: N = 4; controls: N = 3). Observers had to detect a Gabor patch (target) flanked above and below by two high contrast patches (i.e., lateral masking). Stimulus presentation was monocular with durations varying between 133 and 250 ms. Participants underwent 24- 27 training sessions in total. RESULTS: Both PL procedures produced significant improvements in the trained task and learning transferred to visual acuity. Besides, the amount of transfer was greater for the temporal-2AFC task that induced a significant improvement of the contrast sensitivity for untrained spatial frequencies. Most importantly, follow-up tests on MD patients trained with the temporal-2AFC task showed that PL effects were retained between four and six months, suggesting long-term neural plasticity changes in the visual cortex. CONCLUSION: The results show for the first time that PL with a lateral masking configuration has strong, non-invasive and long lasting rehabilitative potential to improve residual vision in the PRL of patients with central vision loss.