Basal forebrain volume and metabolism in carriers of the Colombian mutation for autosomal dominant Alzheimer's disease.

We aimed to study atrophy and glucose metabolism of the cholinergic basal forebrain in non-demented mutation carriers for autosomal dominant Alzheimer's disease (ADAD). We determined the level of evidence for or against atrophy and impaired metabolism of the basal forebrain in 167 non-demented carriers of the Colombian PSEN1 E280A mutation and 75 age- and sex-matched non-mutation carriers of the same kindred using a Bayesian analysis framework. We analyzed baseline MRI, amyloid PET, and FDG-PET scans of the Alzheimer's Prevention Initiative ADAD Colombia Trial. We found moderate evidence against an association of carrier status with basal forebrain volume (Bayes factor (BF10) = 0.182). We found moderate evidence against a difference of basal forebrain metabolism (BF10 = 0.167). There was only inconclusive evidence for an association between basal forebrain volume and delayed memory and attention (BF10 = 0.884 and 0.184, respectively), and between basal forebrain volume and global amyloid load (BF10 = 2.1). Our results distinguish PSEN1 E280A mutation carriers from sporadic AD cases in which cholinergic involvement of the basal forebrain is already detectable in the preclinical and prodromal stages. This indicates an important difference between ADAD and sporadic AD in terms of pathogenesis and potential treatment targets.

Feasibility of a standard cognitive assessment in European academic memory clinics.

INTRODUCTION: Standardized cognitive assessment would enhance diagnostic reliability across memory clinics. An expert consensus adapted the Uniform Dataset (UDS)-3 for European centers, the clinician's UDS (cUDS). This study assessed its implementation acceptability and feasibility. METHODS: We developed a survey investigating barriers, facilitators, and willingness to implement the cUDS. With a mixed-methods design, we analyzed data from academic memory clinics. RESULTS: Seventy-eight percent of responding clinicians were experienced neuropsychologists/psychologists and 22% were medical specialists coming from 18 European countries. Sixty-five percent clinicians were willing to implement cUDS. General barriers related to implementation (43%) and clinical-methodological domains (21%). Favorable clinicians reported finances (15%) and digitalization (9%) as facilitating, but unavailability of local norms (23%) as hindering. Unfavorable clinicians reported logistical (23%) and time issues (18%). DISCUSSION: Despite challenges, data showed moderate clinicians' acceptability and requirements to improve feasibility. Nonetheless, these results come from academic clinicians. The next steps will require feasibility evaluation in non-academic contexts.

Clinical research in dementia: A perspective on implementing innovation.

The increasing global prevalence of dementia demands concrete actions that are aimed strategically at optimizing processes that drive clinical innovation. The first step in this direction requires outlining hurdles in the transition from research to practice. The different parties needed to support translational processes have communication mismatches; methodological gaps hamper evidence-based decision-making; and data are insufficient to provide reliable estimates of long-term health benefits and costs in decisional models. Pilot projects are tackling some of these gaps, but appropriate methods often still need to be devised or adapted to the dementia field. A consistent implementation perspective along the whole translational continuum, explicitly defined and shared among the relevant stakeholders, should overcome the "research-versus-adoption" dichotomy, and tackle the implementation cliff early on. Concrete next steps may consist of providing tools that support the effective participation of heterogeneous stakeholders and agreeing on a definition of clinical significance that facilitates the selection of proper outcome measures.

Harmonizing neuropsychological assessment for mild neurocognitive disorders in Europe.

INTRODUCTION: Harmonized neuropsychological assessment for neurocognitive disorders, an international priority for valid and reliable diagnostic procedures, has been achieved only in specific countries or research contexts. METHODS: To harmonize the assessment of mild cognitive impairment in Europe, a workshop (Geneva, May 2018) convened stakeholders, methodologists, academic, and non-academic clinicians and experts from European, US, and Australian harmonization initiatives. RESULTS: With formal presentations and thematic working-groups we defined a standard battery consistent with the U.S. Uniform DataSet, version 3, and homogeneous methodology to obtain consistent normative data across tests and languages. Adaptations consist of including two tests specific to typical Alzheimer's disease and behavioral variant frontotemporal dementia. The methodology for harmonized normative data includes consensus definition of cognitively normal controls, classification of confounding factors (age, sex, and education), and calculation of minimum sample sizes. DISCUSSION: This expert consensus allows harmonizing the diagnosis of neurocognitive disorders across European countries and possibly beyond.

Neural Suppression Elicited During Motor Imagery Following the Observation of Biological Motion From Point-Light Walker Stimuli.

Introduction: Advantageous effects of biological motion (BM) detection, a low-perceptual mechanism that allows the rapid recognition and understanding of spatiotemporal characteristics of movement via salient kinematics information, can be amplified when combined with motor imagery (MI), i.e., the mental simulation of motor acts. According to Jeannerod's neurostimulation theory, asynchronous firing and reduction of mu and beta rhythm oscillations, referred to as suppression over the sensorimotor area, are sensitive to both MI and action observation (AO) of BM. Yet, not many studies investigated the use of BM stimuli using combined AO-MI tasks. In this study, we assessed the neural response in the form of event-related synchronization and desynchronization (ERD/S) patterns following the observation of point-light-walkers and concordant MI, as compared to MI alone. Methods: Twenty right-handed healthy participants accomplished the experimental task by observing BM stimuli and subsequently performing the same movement using kinesthetic MI (walking, cycling, and jumping conditions). We recorded an electroencephalogram (EEG) with 32 channels and performed time-frequency analysis on alpha (8-13 Hz) and beta (18-24 Hz) frequency bands during the MI task. A two-way repeated-measures ANOVA was performed to test statistical significance among conditions and electrodes of interest. Results: The results revealed significant ERD/S patterns in the alpha frequency band between conditions and electrode positions. Post hoc comparisons showed significant differences between condition 1 (walking) and condition 3 (jumping) over the left primary motor cortex. For the beta band, a significantly less difference in ERD patterns (p < 0.01) was detected only between condition 3 (jumping) and condition 4 (reference). Discussion: Our results confirmed that the observation of BM combined with MI elicits a neural suppression, although just in the case of jumping. This is in line with previous findings of AO and MI (AOMI) eliciting a neural suppression for simulated whole-body movements. In the last years, increasing evidence started to support the integration of AOMI training as an adjuvant neurorehabilitation tool in Parkinson's disease (PD). Conclusion: We concluded that using BM stimuli in AOMI training could be promising, as it promotes attention to kinematic features and imitative motor learning.