Rationale and protocol of the StayFitLonger study: a multicentre trial to measure efficacy and adherence of a home-based computerised multidomain intervention in healthy older adults.

BACKGROUND: In older adults, multidomain training that includes physical and cognitive activities has been associated with improvement of physical and cognitive health. The goal of the multisite StayFitLonger study is to assess a home-based computerised training programme, which combines physical exercises, stimulating cognitive activities and virtual coaching. METHODS: One hundred twenty-eight cognitively healthy older adults will be recruited from the community in Switzerland, Canada and Belgium. The study will comprise (1) a 26-week double-blind randomized controlled efficacy trial and (2) a 22-week pragmatic adherence sub-study. In the efficacy trial, participants will be randomly assigned to an experimental or an active control intervention. In the experimental intervention, participants will use the StayFitLonger programme, which is computerised on a tablet and provides content that combines physical activities with a focus on strength and balance, as well as divided attention, problem solving and memory training. Outcomes will be measured before and after 26 weeks of training. The primary efficacy outcome will be performance on the "Timed-Up & Go" test. Secondary outcomes will include measures of frailty, cognition, mood, fear of falling, quality of life, and activities of daily living. Age, sex, education, baseline cognition, expectation, and adherence will be used as moderators of efficacy. Following the 26-week efficacy trial, all participants will use the experimental programme meaning that participants in the control group will 'cross over' to receive the StayFitLonger programme for 22 weeks. Adherence will be measured in both groups based on dose, volume and frequency of use. In addition, participants' perception of the programme and its functionalities will be characterised through usability, acceptability and user experience. DISCUSSION: This study will determine the efficacy, adherence and participants' perception of a home-based multidomain intervention programme and its functionalities. This will allow for further development and possible commercialization of a scientifically validated training programme. TRIAL REGISTRATION: ClinicalTrials.gov , NCT04237519 Registered on January 22, 2020 - Retrospectively registered.

Increased audiovisual integration in cochlear-implanted deaf patients: independent components analysis of longitudinal positron emission tomography data.

It has been demonstrated in earlier studies that patients with a cochlear implant have increased abilities for audio-visual integration because the crude information transmitted by the cochlear implant requires the persistent use of the complementary speech information from the visual channel. The brain network for these abilities needs to be clarified. We used an independent components analysis (ICA) of the activation (H2(15)O) positron emission tomography data to explore occipito-temporal brain activity in post-lingually deaf patients with unilaterally implanted cochlear implants at several months post-implantation (T1), shortly after implantation (T0) and in normal hearing controls. In between-group analysis, patients at T1 had greater blood flow in the left middle temporal cortex as compared with T0 and normal hearing controls. In within-group analysis, patients at T0 had a task-related ICA component in the visual cortex, and patients at T1 had one task-related ICA component in the left middle temporal cortex and the other in the visual cortex. The time courses of temporal and visual activities during the positron emission tomography examination at T1 were highly correlated, meaning that synchronized integrative activity occurred. The greater involvement of the visual cortex and its close coupling with the temporal cortex at T1 confirm the importance of audio-visual integration in more experienced cochlear implant subjects at the cortical level.

[Specificities of the logopenic variant of primary progressive aphasia]. / Particularités du variant logopénique au sein des aphasies progressives primaires.

The logopenic variant of primary progressive aphasia is a syndrome with neuropsychological and linguistic specificities, including phonological loop impairment for which diagnosis is currently mainly based on the exclusion of the two other variants, semantic and nonfluent/agrammatic primary progressive aphasia. The syndrome may be underdiagnosed due (1) to mild language difficulties during the early stages of the disease or (2) to being mistaken for mild cognitive impairment or Alzheimer's disease when the evaluation of episodic memory is based on verbal material and (3) finally, it is not uncommon that the disorders are attributed to psychiatric co-morbidities such as, for example, anxiety. Moreover, compared to other variants of primary progressive aphasia, brain abnormalities are different. The left temporoparietal junction is initially affected. Neuropathology and biomarkers (cerebrospinal fluid, molecular amyloid nuclear imaging) frequently reveal Alzheimer's disease. Consequently this variant of primary progressive aphasia does not fall under the traditional concept of frontotemporal lobar degeneration. These distinctive features highlight the utility of correct diagnosis, classification, and use of biomarkers to show the neuropathological processes underlying logopenic primary progressive aphasia. The logopenic variant of primary progressive aphasia is a specific form of Alzheimer's disease frequently presenting a rapid decline; specific linguistic therapies are needed. Further investigation of this syndrome is needed to refine screening, improve diagnostic criteria and better understand the epidemiology and the biological mechanisms involved.

[Diabetes and dementia: the dangerous liaisons? ]. / Diabéte et démence: tes liaisons dangereuses?

As population ages, a growing number of older patients present the constellation of diabetes and dementia. Numerous recent studies highlight that diabetes may increase the risk for Alzheimer and vascular dementia. Among patients with previous severe hypoglycemia, that risk may even double. Inversely demented patients have about three times higher risk of hypoglycemia. Given that spiral link between hypoglycemia and dementia, the latter should be considered as a possible complication of diabetes and consistently be screened for among older diabetic patients. Furthermore, the American Diabetes Association and American Geriatric Society consensus recommends a more flexible glycemic treatment goal of AIC among demented patients, with a target range between 8 and 9%.

[2012: news in neurology]. / Neurologie.

In 2012, intramuscular midazolam appears as effective as intravenous lorezepam for the first line treatment of convulsive status epilepticus. Perampanel, a new anti-epileptic drug, will be soon available. Two oral treatments are now available for stroke prevention in atrial fibrillation setting. The methylphenidate and the Tai Chi could increase the walk capacity of patients suffering from Parkinson disease. A comprehensive cardiac work-up is essential for some congenital myopathy. A new drug against migraine seems free from vasoconstrictive effect. Antioxidants are harmful in Alzheimer disease. Some oral medication will be available for multiple sclerosis.

Pre-frail older adults show improved cognition with StayFitLonger computerized home-based training: a randomized controlled trial.

Multidomain interventions have shown tremendous potential for improving cognition in older adults. It is unclear if multidomain interventions can be delivered remotely and whether remote intervention is beneficial for older adults who are vulnerable or at risk of cognitive decline. In a 26-week multi-site, home-based, double-blind, randomized controlled trial, 120 cognitively healthy older adults (75 robust, 45 pre-frail; age range = 60-94) recruited from Switzerland, Canada, and Belgium were randomized to receive either the StayFitLonger (SFL) computerized multidomain training program or an active control intervention. Delivered on tablets, the SFL intervention combined adapted physical exercises (strength, balance, and mobility), cognitive training (divided attention, problem solving, and memory), opportunities for social and contributive interactions, and psychoeducation. The active control intervention provided basic mobilization exercises and access to video games. Cognitive outcomes were global cognition (Z-scores of attention, verbal fluency, and episodic memory for nondemented older adults; ZAVEN), memory, executive function, and processing speed. Linear mixed model analyses indicated improved performance on the ZAVEN global cognition score in the SFL group but not in the active control group. Stratified analyses by frailty status revealed improved ZAVEN global cognition and processing speed scores following SFL in the pre-frail group but not in the robust group. Overall, the study indicates that a computerized program providing a multidomain intervention at home can improve cognition in older adults. Importantly, pre-frail individuals, who are at higher risk of cognitive decline, seem to benefit more from the intervention. Trial registration: ClinicalTrials.gov, NCT037519 Registered on January 22, 2020-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04237519 .

Neuropsychological outcome after a first symptomatic ischaemic stroke with 'good recovery'.

BACKGROUND: Neuropsychological impairment after stroke when no motor, sensory or language deficits are left remains understudied. The primary aim of this study was to assess neuropsychological outcome in a specific population of patients after a first symptomatic stroke without previous cognitive decline and with a good motor, linguistic, and functional recovery (i.e. 'good outcome'). The secondary aims were to identify the profile of this potential impairment and relations between brain lesions and neuropsychological outcome. METHODS: Sixty consecutive patients were evaluated by a comprehensive neuropsychological assessment focusing specifically on executive and attentional functions but also on memory 109 days, on average, after the infarct. Patients were compared with 40 healthy controls matched for age and education. RESULTS: Patients showed lower performance in every cognitive domain compared with controls. Along with an important executive deficit, patients were also impaired on attention and memory. Patients were not more depressed than controls, although they were more apathetic. We also found a significant positive correlation between cognitive impairment and pre-existing white matter brain lesions assessed by MRI. CONCLUSIONS: We report the first study examining the impact of a first stroke on cognition but also on psychiatric disorders in patients with good functional outcome. We found that patients considered as asymptomatic were, in fact, exhibiting a multidomain cognitive deficit that could impact return to life as before stroke.

[Neurology]. / Neurologie.

In 2011, new oral anticoagulants for atrial fibrillation are available and the ABCD3-I score predicting stroke after TIA updates the ABCD2 score. New McDonald criteria allow faster MS diagnosis and the first oral treatment (fingolimod) for MS can be prescribed. A new anti-antiepileptic drug (retigabine) is available and sodium valproate has long term neurological adverse effects after in utero exposure. Among Parkinson disease treatments, deep brain stimulation is extending applications and dopamine agonists with extended release are as efficient and well tolerated as standard forms at long term scale. Monoclonal antibodies and immunosuppressant agents are proposed as good alternatives in the treatment of chronic dysimmune polyneuropathies. Gene therapy for the treatment of genetic myopathies is progressing.

Does brain activity at rest reflect adaptive strategies? Evidence from speech processing after cochlear implantation.

In functional neuroimaging studies, task-related activity refers to the signal difference between the stimulation and rest conditions. We asked whether long-term changes in the sensory environment may affect brain activity at rest. To answer this question, we compared regional cerebral blood flow between a group of normally hearing controls and a group of cochlear-implanted (CI) deaf patients. Here we present evidence that long-term alteration of auditory experience, such as profound deafness followed by partial auditory recuperation through cochlear implantation, leads to functional cortical reorganizations at rest. Without any visual or auditory stimulation, CI subjects showed changes of cerebral blood flow in the visual, auditory cortex, Broca area, and in the posterior temporal cortex with an increment of activity in these areas from the time of activation of the implant to less than a year after the implantation.

Temporal analysis of regional anaesthesia-induced sensorimotor dysfunction: a model for understanding phantom limb.

BACKGROUND: The peripheral deafferentation induced by regional anaesthesia (RA) results in misperception of size-shape (S) and posture (P) of the anesthetized limb. During RA, most patients seem to describe motionless 'phantom limbs' fixed in stereotyped illusory positions, suggesting that RA could unmask stable postural patterns. The question of whether movement illusions exist or not after anaesthesia needs a prospective study. This study aimed to describe the phenomenology of RA-induced kinesthetic illusions (K illusions). METHODS: We examined prospectively the body image alteration during infraclavicular blocks in 20 patients. Multimodal sensory testing (pinprick, heat-cold, pallesthesia, and arthrokinesia) and assessment of motor function were performed every 5 min for 60 min after administration of the local anaesthetics. Meanwhile, patients described phantom limb sensations (S, P, and K illusions). RESULTS: We individualized the occurrence of K illusions [44 (8) min] with respect to S illusions [7 (3) min; P<0.005] and P illusions [22 (4) min; P<0.001]. A close relationship between the onset of K illusions and proprioceptive impairment (arthrokinesia: r=0.92, P<0.001; pallesthesia: r=0.89, P<0001) and abolishment of motor activity (r=0.83, P<0.001) was identified. Finally, a principal component analysis showed that S and P illusions were essentially related to the proprioceptive impairment. CONCLUSIONS: This study analyses for the first time the temporal evolution of sensorimotor dysfunction and the onset of K illusions during RA. Our results suggest the involvement of an alteration of proprioception and motor functions in the origin of this phenomenon. These data agree with the motor awareness theory.

Left premotor cortex and allophonic speech perception in dyslexia: a PET study.

Disorders of categorical perception has been put forward as a new account of phonological deficit in dyslexia (Serniclaes, W., Sprenger-Charolles, L., Carre, R. and Demonet, J.F., 2001. Perceptual discrimination of speech sounds in developmental dyslexia. J. Speech Lang. Hear. Res. 44, 384-399.) so that dyslexic subjects tend to discriminate phoneme instances within a given phonemic category rather than between categories, possibly witnessing the persistence of phonemic boundaries of 'allophones' that may be relevant to other languages although not to one's mother tongue (Serniclaes, W., Van Heghe, S., Mousty, P., Carre, R. and Sprenger-Charolles, L., 2004. Allophonic mode of speech perception in dyslexia. J. Exp. Child Psychol. 87, 336-361.). The brain correlates of within- and between-category discrimination were explored using a /ba/-/da/ phonetic continuum and H(2)(15)O PET in 14 dyslexic and 16 control adult readers; subjects discriminated a set of stimuli pairs, first in a 'naïve' (acoustic) condition and, after debriefing about the stimuli identity, in a speech (phonemic) condition (Dufor, O., Serniclaes, W., Sprenger-Charolles, L. and Demonet, J.F., 2007. Top-down processes during auditory phoneme categorization in dyslexia: a PET study. NeuroImage 34, 1692-1707.). While discrimination of 'between' pairs improved in all subjects following debriefing, 'within' stimuli yielded variable performance; some subjects kept discriminating them, while best categorizers judged them identical. Correlation analyses between acoustic-to-speech changes in brain activity and in 'within'-pair discrimination, and between control and dyslexic groups, revealed a criss-crossed correlation pattern in the left BA6 so that the higher the activity the better the categorization in control subjects whereas the higher the activity the more increased 'within' discrimination in dyslexic subjects. Therefore, in average readers, enhanced activity in the left BA6 likely contributes to optimizing phoneme categorization via refined speech motor coding. In dyslexic subjects showing sensitivity to 'within'-category cues, activity enhancement in this region might suggest the persistence of motor coding for allophonic representations of speech.

Dyslexia: cultural diversity and biological unity.

The recognition of dyslexia as a neurodevelopmental disorder has been hampered by the belief that it is not a specific diagnostic entity because it has variable and culture-specific manifestations. In line with this belief, we found that Italian dyslexics, using a shallow orthography which facilitates reading, performed better on reading tasks than did English and French dyslexics. However, all dyslexics were equally impaired relative to their controls on reading and phonological tasks. Positron emission tomography scans during explicit and implicit reading showed the same reduced activity in a region of the left hemisphere in dyslexics from all three countries, with the maximum peak in the middle temporal gyrus and additional peaks in the inferior and superior temporal gyri and middle occipital gyrus. We conclude that there is a universal neurocognitive basis for dyslexia and that differences in reading performance among dyslexics of different countries are due to different orthographies.

Asymmetry of voice onset time-processing in adult developmental dyslexics.

OBJECTIVE: The human auditory cortex codes speech temporally according to sequential acoustico-phonetic cues like the voice onset time (VOT). This coding is predominantly left-lateralized in normal readers. We examined VOT-processing asymmetries in adults with a history of developmental dyslexia (DD-history+). METHODS: Auditory-evoked potentials (AEPs) to voiced (/ba/) and voiceless (/pa/) speech stimuli were recorded from 10 DD-history+ adults and 8 controls. Source modelling of the "release component" (RC: approximately 240 ms; time-locked to voiced consonantal release and considered reflective of VOT-processing) was conducted to explore VOT asymmetries. RESULTS: Controls demonstrated L>R RC source probe amplitude asymmetry in the auditory cortex. DD-history+ subjects with little persistent reading deficit (n=5) demonstrated normal temporal coding but rightward asymmetry. DD-history+ subjects with severe persistent deficits (n=5) exhibited numerous supplemental AEP components (notably left hemispheric) and inconsistent asymmetry (leftward or alternating). CONCLUSIONS: These preliminary findings suggest that DD-history+ adults process auditory speech cues differently than adults without previous DD. The nature of this processing may relate to the severity of persistent reading deficits. SIGNIFICANCE: Previous dyslexics with little persistent deficit can exhibit atypical functional asymmetry with normal auditory temporal coding. Source modelling represents an effective, non-invasive means of exploring processing asymmetries in clinical populations.

[Functional neuroimaging and the treatment of aphasia: speech therapy and repetitive transcranial magnetic stimulation]. / Imagerie fonctionnelle cérébrale et prise en charge thérapeutique de l'aphasie : orthophonie et stimulation magnétique transcrânienne répétitive.

Functional imaging has provided new evidence of the neurobiological impact of the treatment of aphasia, including speech therapy, through the alteration of the activated language neural network. In such a way, speech therapy has proved its impact. The role of each hemisphere is still very unclear. Some of the authors link the left-lateralisation of activations to the therapeutic improvement of language and the right-activated network to a maladaptative strategy, whereas others consider the latter as a useful compensatory network for speech disorders. Repetitive trans-cranial magnetic stimulation (rTMS), first used to determine cortical activity, is now used to directly interfere with cerebral activity. In the years to come, rTMS should be developed as an adjuvant therapy for aphasia.

Lateral masking, levels of processing and stimulus category: a comparative study between normal and dyslexic readers.

The lateral masking effect results in lower performance on letter recognition when items are flanked by other stimuli. Using a new paradigm based on discrimination (feature analysis) and categorization (memory access) tasks, we investigated the influence of level of processing (as addressed, respectively, by these two tasks) and stimulus type (Latin letters, Korean letters and geometrical figures) on lateral masking. In addition, performance of dyslexic and non-dyslexic adult readers was compared. The non-dyslexic participants demonstrated a classical lateral masking effect with lower performance for flanked items than isolated ones. In addition, lateral masking was stronger in the categorization than in the discrimination task and was restricted to familiar items, i.e., Latin letters and geometrical figures. Dyslexic participants showed poorer performance than non-dyslexics on processing isolated items, and the pattern of decrease in performance for lateral masking was similar to non-dyslexics. However, they also showed a stronger decrease in performance in categorization and a stronger decrease related to the lateral masking for this categorization task. Our results in normal readers suggest that lateral masking relies on the interference between the target and the flankers during feature integration that may result in marked impairment of memory access (categorization task). Poorer performance in dyslexic readers may reflect impaired parafoveal/peripheral low-level processing during feature integration that may have worsened during the flanked condition due to a target selection/spatial-attentional disorder. Moreover, dyslexic subjects presented an additional categorization deficit that may relate to a specific left-hemispheric disorder.

Brain abnormalities underlying altered activation in dyslexia: a voxel based morphometry study.

Voxel-based morphometry was used to assess the consistency among functional imaging and brain morphometry data in developmental dyslexia. Subjects, from three different cultural contexts (UK, France and Italy), were the same as those described in a previous PET activation paper, which revealed a common pattern of reduced activation during reading tasks in the left temporal and occipital lobes. We provide evidence that altered activation observed within the reading system is associated with altered density of grey and white matter of specific brain regions, such as the left middle and inferior temporal gyri and the left arcuate fasciculus. This supports the view that dyslexia is associated with both local grey matter dysfunction and with altered connectivity among phonological/reading areas. The differences were replicable across samples confirming that the neurological disorder underlying dyslexia is the same across the cultures investigated in the study.

CTP in Transient Global Amnesia: A Single-Center Experience of 30 Patients.

BACKGROUND AND PURPOSE: Medial temporal lobe abnormalities on DWI and functional imaging are occasionally observed in patients with transient global amnesia. We used CTP to study these patients during or briefly after resolution of their amnesic syndrome. MATERIALS AND METHODS: From 2002 onward, patients satisfying clinical criteria for transient global amnesia who underwent CTP were included. Patients with additional clinical features suggesting transient ischemic attack or stroke and those with an ischemic lesion on subsequent DWI were excluded. If deemed necessary by the clinician, DWI was performed within 10 days. RESULTS: Thirty patients with transient global amnesia underwent CTP at a median latency of 5.9 hours (interquartile range, 4.3-9.7 hours) after symptom onset. All findings, except for those in 1 patient, were normal, including those in the 14 patients with well-imaged hippocampi. In the patient with abnormal findings, CTP and PWI showed hypoperfusion in both lentiform nuclei extending into the insulae, with normalization on the repeat CTP 6 days later. In 10 patients, DWI was performed at a median latency of 2 days (interquartile range, 0-9 days). Of these, 2 showed punctate hippocampal lesions, often seen in transient global amnesia. In 2 patients excluded because of mildly atypical transient global amnesia and ischemic lesions on subsequent DWI, acute CTP findings were also normal. CONCLUSIONS: Patients with transient global amnesia had normal CTP findings in the acute phase with the exception of 1 patient with transient hypoperfusion in both basal ganglia. If imaging is performed for typical and atypical transient global amnesia, DWI should be the preferred method.

Activation of regional cerebral blood flow by a memorization task in early Parkinson's disease patients and normal subjects.

Task-induced changes in regional cerebral blood flow (rCBF) during memory activation were compared in 18 right-handed patients with early Parkinson's disease (PD) and 20 normal volunteers using the same activation paradigm. We used single-photon emission computed tomography and 133Xe in 21 regions of interest during rest, passive listening of a work list, and memorization of another word list, which was followed by a free recall test immediately after completion of the rCBF measurement. The average performance on free recall was not significantly lower in PD patients than in controls. In normal subjects, five left-sided regions (anterior middle frontal, posterior inferior frontal, superior middle temporal, thalamic, and lenticular) showed a significant increase in memorizing compared to passive listening. This pattern of activation suggests the existence of a verbal rehearsal strategy during the memorization task in normals. In PD patients, increases in these regions did not reach significance, whereas significant activations were noted in superior prefrontal regions. Such alterations in the pattern of activation in PD patients, despite a memory performance similar to that of controls are viewed as a consequence of an early dysfunction of the articulatory loop system and of compensatory mechanisms in other parts of the frontal lobe emerging in the early stages of the disease.