Musical and psychomotor interventions for cognitive, sensorimotor, and cerebral decline in patients with Mild Cognitive Impairment (COPE): a study protocol for a multicentric randomized controlled study.

BACKGROUND: Regular cognitive training can boost or maintain cognitive and brain functions known to decline with age. Most studies administered such cognitive training on a computer and in a lab setting. However, everyday life activities, like musical practice or physical exercise that are complex and variable, might be more successful at inducing transfer effects to different cognitive domains and maintaining motivation. "Body-mind exercises", like Tai Chi or psychomotor exercise, may also positively affect cognitive functioning in the elderly. We will compare the influence of active music practice and psychomotor training over 6 months in Mild Cognitive Impairment patients from university hospital memory clinics on cognitive and sensorimotor performance and brain plasticity. The acronym of the study is COPE (Countervail cOgnitive imPairmEnt), illustrating the aim of the study: learning to better "cope" with cognitive decline. METHODS: We aim to conduct a randomized controlled multicenter intervention study on 32 Mild Cognitive Impairment (MCI) patients (60-80 years), divided over 2 experimental groups: 1) Music practice; 2) Psychomotor treatment. Controls will consist of a passive test-retest group of 16 age, gender and education level matched healthy volunteers. The training regimens take place twice a week for 45 min over 6 months in small groups, provided by professionals, and patients should exercise daily at home. Data collection takes place at baseline (before the interventions), 3, and 6 months after training onset, on cognitive and sensorimotor capacities, subjective well-being, daily living activities, and via functional and structural neuroimaging. Considering the current constraints of the COVID-19 pandemic, recruitment and data collection takes place in 3 waves. DISCUSSION: We will investigate whether musical practice contrasted to psychomotor exercise in small groups can improve cognitive, sensorimotor and brain functioning in MCI patients, and therefore provoke specific benefits for their daily life functioning and well-being. TRIAL REGISTRATION: The full protocol was approved by the Commission cantonale d'éthique de la recherche sur l'être humain de Genève (CCER, no. 2020-00510) on 04.05.2020, and an amendment by the CCER and the Commission cantonale d'éthique de la recherche sur l'être humain de Vaud (CER-VD) on 03.08.2021. The protocol was registered at clinicaltrials.gov (20.09.2020, no. NCT04546451).

EEG markers are associated to gray matter changes in thalamus and basal ganglia in subjects with mild cognitive impairment.

BACKGROUND: Gray matter (GM) changes of thalamus and basal ganglia have been demonstrated to be involved in Alzheimer's disease (AD). Moreover, the increase of two EEG markers, alpha3/alpha2 and theta/gamma ratio, have been associated with, respectively, AD converter and non-AD converter subjects with mild cognitive impairment (MCI). OBJECTIVE: To study the association of prognostic EEG markers with specific GM changes of thalamus and basal ganglia in subjects with MCI to identify different MCI populations. METHODS: 74 adult subjects with mild cognitive impairment underwent EEG recording and high resolution 3D magnetic resonance imaging (MRI). The theta/gamma and alpha3/alpha2 ratio was computed for each subject. Three groups were obtained according to increasing tertile values of both alpha3/alpha2 and theta/gamma ratio. Gray matter density differences between groups were investigated using a voxel-based morphometry technique. RESULTS: Subjects with higher a3/a2 ratios when compared to subjects with lower and middle a3/a2 ratios showed minor atrophy in the ventral stream of basal ganglia (head of caudate nuclei and accumbens nuclei bilaterally) and of the pulvinar nuclei in the thalamus; subjects with higher t/g ratio showed minor atrophy in putamina nuclei bilaterally than subjects with middle ratio. CONCLUSION: The integrated analysis of EEG and morpho-structural markers could be useful in the comprehension of anatomo-physiological underpinning of the MCI entity.

Neuroimaging outcomes in clinical trials in Alzheimer's disease.

The first disease modifying drugs targeting beta amyloid that were tested in phase II and III clinical trials have been disappointing. We believe that failures descended from a leaky drug development pipeline where insufficient attention has been devoted to valid animal models and valid imaging markers of disease progression. In the future, valid animal models will need to take into greater consideration the natural and molecular history of AD, where both beta amyloid and tau play a key role. Valid imaging markers of disease progression will need to be identified in humans and translated into animal versions. Future testing of putative disease modifying drugs in valid animal models with valid imaging markers of disease progression will allow to maximize the predictability of their effect in phase II and III clinical trials.

[Music therapy in Alzheimer's disease: is an evidence-based approach possible?]. / Musicoterapia nella malattia di Alzheimer: è possibile un approccio basato sull'evidenza?

The application of music therapy to Alzheimer's patients is relatively recent. The studies available in literature show that music therapy has a positive effect either on mood or cognition. However, the generalization of data is difficult because these researches have lacked methodological design rigour. Based on the application of this rehabilitative technique in our Alzheimer Unit in Brescia and on the recent researches of music neuroanatomy, this work tries to identify which processes are involved in the therapeutic effect of music therapy. Despite the perceived effect on mood and socialisation abilities, cultural and methodological problems hinder to demonstrate the efficacy of music therapy. Information about neurophysiological and neurochemical correlates of music therapy are so poor that the use of this technique is often based on the assumption that the supposed positive effect of music is enough to justify its application. The methodological problem is related to the evaluation of outcomes. The fact that those studies which investigated the effects of music therapy were characterized by less specific indicators (cognition, behavior) and by less standardized instruments made difficult to generalize and quantify the results. The aim of the study is to organize the present knowledge with a systematic approach so that further researches lead to base the application of music therapy on evidence instead of on singular clinical finding.

Vertebrobasilar ischemia after neck motion.

BACKGROUND: Vertebrobasilar ischemic strokes may occur after chiropractic manipulation of the cervical spine or, less often, after spontaneous and abrupt head movement. SUMMARY OF REVIEW: We describe three such cases of vertebrobasilar ischemic strokes and review 36 other reported cases. CONCLUSIONS: We give evidence that 1) the population at risk cannot be identified a priori in the vast majority of cases; 2) symptoms may develop after many uneventful manipulations; 3) clinical syndromes consist of occipital lobe (5%), cerebellar (8%), locked-in (8%), Wallenberg's (28%), other brain stem (49%), and unclassifiable (2%); 4) mortality or very severe long-term impairment occurs in 28% of cases; 5) the development of transient neurological symptoms during previous manipulations, the presence of known or suspected ligament laxity, and, if known, the presence of a vertebral artery terminating in posterior inferior cerebellar artery should always contraindicate any chiropractic neck maneuver; and 6) the pathogenetic mechanism involves vertebral artery dissection at the atlantoaxial joint with intimal tear, intramural bleeding, or pseudoaneurysm that can lead to thrombosis or embolism.