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 .

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.

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.

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.

Effect of levodopa on both verbal and motor representations of action in Parkinson's disease: a fMRI study.

Previous studies have demonstrated that non-demented Parkinson's disease (PD) patients have a specific impairment of verb production compared with noun generation. One interpretation of this deficit suggested the influence of striato-frontal dysfunction on action-related verb processing. The aim of our study was to investigate cerebral changes after motor improvement due to dopaminergic medication on the neural circuitry supporting action representation in the brain as mediated by verb generation and motor imagery in PD patients. Functional magnetic resonance imaging on 8 PD patients in "ON" dopaminergic treatment state (DTS) and in "OFF" DTS was used to explore the brain activity during three different tasks: Object Naming (ObjN), Generation of Action Verbs (GenA) in which patients were asked to overtly say an action associated with a picture and mental simulation of action (MSoA) was investigated by asking subjects to mentally simulate an action related to a depicted object. The distribution of brain activities associated with these tasks whatever DTS was very similar to results of previous studies. The results showed that brain activity related to semantics of action is modified by dopaminergic treatment in PD patients. This cerebral reorganisation concerns mainly motor and premotor cortex suggesting an involvement of the putaminal motor loop according to the "motor" theory of verb processing.

[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.

Neural dissociation of phonological and visual attention span disorders in developmental dyslexia: FMRI evidence from two case reports.

A dissociation between phonological and visual attention (VA) span disorders has been reported in dyslexic children. This study investigates whether this cognitively-based dissociation has a neurobiological counterpart through the investigation of two cases of developmental dyslexia. LL showed a phonological disorder but preserved VA span whereas FG exhibited the reverse pattern. During a phonological rhyme judgement task, LL showed decreased activation of the left inferior frontal gyrus whereas this region was activated at the level of the controls in FG. Conversely, during a visual categorization task, FG demonstrated decreased activation of the parietal lobules whereas these regions were activated in LL as in the controls. These contrasted patterns of brain activation thus mirror the cognitive disorders' dissociation. These findings provide the first evidence for an association between distinct brain mechanisms and distinct cognitive deficits in developmental dyslexia, emphasizing the importance of taking into account the heterogeneity of the reading disorder.

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.

Verb production during action naming in semantic dementia.

UNLABELLED: In contrast with widely documented deficits of semantic knowledge relating to object concepts and the corresponding nouns in semantic dementia (SD), little is known about action semantics and verb production in SD. The degradation of action semantic knowledge was studied in 5 patients with SD compared with 17 matched control participants in an action naming task based on video clips. The pattern of errors, involving a huge proportion of generic verbs (e.g. "to remove" versus "to peel") relative to responses in control subjects, suggested a hierarchical, bottom-up deficit of action knowledge in SD patients. In addition, abnormal responses in patients consisted of verbs that were semantically related to the expected verbs produced by control subjects (e.g. "to undress" versus "to peel" for the action [To peel_orange]). This study suggests that, in SD, non-canonical responses to action naming reflect lack of both specificity and semantic relatedness relative to the expected responses. LEARNING OUTCOMES: As a result of this activity, readers will recognize that semantic word knowledge disappears in semantic dementia using video clips of object-related actions. As a result of this activity, readers will discover that this semantic impairment followed a hierarchical pattern with the more specific verbs vanishing first.

Superior parietal lobule dysfunction in a homogeneous group of dyslexic children with a visual attention span disorder.

A visual attention (VA) span disorder has been reported in dyslexic children as potentially responsible for their poor reading outcome. The purpose of the current paper was to identify the cerebral correlates of this VA span disorder. For this purpose, 12 French dyslexic children with severe reading and VA span disorders and 12 age-matched control children were engaged in a categorisation task under fMRI. Two flanked and isolated conditions were designed which both involved multiple-element simultaneous visual processing but taxed visual attention differently. For skilled readers, flanked stimuli processing activated a large bilateral cortical network comprising the superior and inferior parietal cortex, the inferior temporal cortex, the striate and extrastriate visual cortex, the middle frontal cortex and the anterior cingulate cortex while the less attention-demanding task of isolated stimuli only activated the inferior occipito-temporal cortex bilaterally. With respect to controls, the dyslexic children showed significantly reduced activation within bilateral parietal and temporal areas during flanked processing, but no difference during the isolated condition. The neural correlates of the processes involved in attention-demanding multi-element processing tasks were more specifically addressed by contrasting the flanked and the isolated conditions. This contrast elicited activation of the left precuneus/superior parietal lobule in the controls, but not in the dyslexic children. These findings provide new insights on the role of parietal regions, in particular the left superior parietal lobule, in the visual attention span and in developmental dyslexia.

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.

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.

Good recovery from aphasia is also supported by right basal ganglia: a longitudinal controlled PET study. EJPRM-ESPRM 2008 award winner.

AIM: It has long been a matter of debate whether recovery from aphasia after left perisylvian lesion is mediated by perilesional left hemispheric regions or by right homologous areas. To investigate the neural substrates of aphasia recovery, a longitudinal study in patients after a left single perisylvian stroke was performed. METHODS: Thirteen aphasic patients were H2(15)O PET-scanned twice at a one year interval during a word generation task. Patients are divided into two groups according to language performance for the word generation task at PET2. For the Good Recovery (GR) group, patients' performances are indistinguishable from those of normal subjects, while patients from the Poor Recovery (PR) group keep language disorders. Using SPM2, Language-Rest contrast is computed for both groups at both PET stages. Then, Session Effect contrast (TEP2-TEP1>0) is calculated for both groups. RESULTS: For the GR group, the Session Effect contrast shows an increase of activations in the left Postero-Superior Temporal Gyrus PSTG but also in the right thalamus and lenticular nuclei; for PR patients, the right lenticular nucleus activation is more important at PET1 than PET2. CONCLUSIONS: The crucial role of the left temporal activation is confirmed and its increase is linked to behavioural recovery. The role of the right basal ganglia to support good recovery from aphasia is a new finding. Their activation may be more task-dependant and related to inhibition of the right frontal cortex.

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.

[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.