Development and validation of an instrument for measuring parkinsonian motor impairment: TRAPS-D.

BACKGROUND: Parkinson's disease is incurable, idiopathic, degenerative, and progressive, and affects about 1% of the elderly population. Multidisciplinary clinical treatment is the best and most adopted therapeutic option, while surgical treatment is used in less than 15% of those affected. In practice, there is a lack of reliable and validated scales for measuring motor impairment, and monitoring and screening for surgical indications. OBJECTIVE: To develop and validate an instrument for measuring parkinsonian motor impairment in candidates for neurosurgical treatment. METHOD: The development and validation methods followed published guidelines. The first part was the choice of domains that would make up the construct: cardinal signs of disease (tremor, rigidity (stiffness), posture/balance/gait, hypokinesia/akinesia, and speech), along with pain and dyskinesia. A multi-professional working group prepared an initial pilot instrument. Ten renowned specialists evaluated, judged, and suggested modifications to the instrument. The second phase was the evaluation of the content of each domain and the respective ability to classify commitment intensity. The third phase was the correction of the main flaws detected and new submission to the board. The instrument was applied to 41 candidates for neurosurgical treatment in two situations: with and without medication RESULTS: The final form received 100% agreement from the judges. Its average time for application was 8 min. It was very responsive (p = 0.001, Wilcoxon) in different situations (On-Off). CONCLUSION: TRASP-D is a valid instrument for measuring motor impairment in patients with Parkinson's disease who are candidates for neurosurgical treatment. It allows measurement in multiple domains with reliability and sensitivity.

Dementia in Latin America: Paving the way toward a regional action plan.

Across Latin American and Caribbean countries (LACs), the fight against dementia faces pressing challenges, such as heterogeneity, diversity, political instability, and socioeconomic disparities. These can be addressed more effectively in a collaborative setting that fosters open exchange of knowledge. In this work, the Latin American and Caribbean Consortium on Dementia (LAC-CD) proposes an agenda for integration to deliver a Knowledge to Action Framework (KtAF). First, we summarize evidence-based strategies (epidemiology, genetics, biomarkers, clinical trials, nonpharmacological interventions, networking, and translational research) and align them to current global strategies to translate regional knowledge into transformative actions. Then we characterize key sources of complexity (genetic isolates, admixture in populations, environmental factors, and barriers to effective interventions), map them to the above challenges, and provide the basic mosaics of knowledge toward a KtAF. Finally, we describe strategies supporting the knowledge creation stage that underpins the translational impact of KtAF.

Correction to: Brain PET amyloid and neurodegeneration biomarkers in the context of the 2018 NIA-AA research framework: an individual approach exploring clinical-biomarker mismatches and sociodemographic parameters.

In the last paragraph of the subsession "Recruitment of the study population and clinical Evaluation" (Material and methods session).

Brain PET amyloid and neurodegeneration biomarkers in the context of the 2018 NIA-AA research framework: an individual approach exploring clinical-biomarker mismatches and sociodemographic parameters.

PURPOSE: [18F]FDG-PET and [11C]PIB-PET are validated as neurodegeneration and amyloid biomarkers of Alzheimer's disease (AD). We used a PET staging system based on the 2018 NIA-AA research framework to compare the proportion of amyloid positivity (A+) and hypometabolism ((N)+) in cases of mild probable AD, amnestic mild cognitive impairment (aMCI), and healthy controls, incorporating an additional classification of abnormal [18F]FDG-PET patterns and investigating the co-occurrence of such with A+, exploring [18F]FDG-PET to generate hypotheses in cases presenting with clinical-biomarker "mismatches." METHODS: Elderly individuals (N = 108) clinically classified as controls (N = 27), aMCI (N = 43) or mild probable AD (N = 38) were included. Authors assessed their A(N) profiles and classified [18F]FDG-PET neurodegenerative patterns as typical or non-typical of AD, performing re-assessments of images whenever clinical classification was in disagreement with the PET staging (clinical-biomarker "mismatches"). We also investigated associations between "mismatches" and sociodemographic and educational characteristics. RESULTS: AD presented with higher rates of A+ and (N)+. There was also a higher proportion of A+ and (N)+ individuals in the aMCI group in comparison to controls, however without statistical significance regarding the A staging. There was a significant association between amyloid positivity and AD (N)+ hypometabolic patterns typical of AD. Non-AD (N)+ hypometabolism was seen in all A- (N)+ cases in the mild probable AD and control groups and [18F]FDG-PET patterns classified such individuals as "SNAP" and one as probable frontotemporal lobar degeneration. All A- (N)- cases in the probable AD group had less than 4 years of formal education and lower socioeconomic status (SES). CONCLUSION: The PET-based staging system unveiled significant A(N) differences between AD and the other groups, whereas aMCI and controls had different (N) staging, explaining the cognitive impairment in aMCI. [18F]FDG-PET could be used beyond simple (N) staging, since it provided alternative hypotheses to cases with clinical-biomarker "mismatches." An AD hypometabolic pattern correlated with amyloid positivity. Low education and SES were related to dementia in the absence of biomarker changes.

Response letter: Neuropsychiatric presentation of Covid-19-related encephalitis: Case report.

Covid-19-related encephalitis is a heterogeneous syndrome characterized by a combination of clinical, laboratory, and imaging features related to inflammation of the brain, where the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is presumably the causative agent. We reported a case of Covid-19-related encephalitis presenting with neuropsychiatric symptoms, including intense agitation. Reverse-transcriptase polymerase-chain-reaction in cerebrospinal fluid was positive for SARS-CoV-2. Our case expands the literature about neurologic manifestations of Covid-19 and emphasizes the possibility of prominent behavioral symptoms as the initial manifestation.

In vivo imaging evidence of poor cognitive resilience to Alzheimer's disease pathology in subjects with very low cognitive reserve from a low-middle income environment.

INTRODUCTION: Reduced cognitive reserve (CR) due to very low educational (VLE) levels may influence high dementia rates in low-middle income environments, leading to decreased cognitive resilience (RES) to Alzheimer´s disease (AD) pathology. However, in vivo findings in VLE groups confirming this prediction are lacking. METHODS: Cognitively impaired patients (with clinically defined AD dementia or amnestic mild cognitive impairment) and cognitively unimpaired older adults (n = 126) were recruited for a positron emission tomography (PET) and magnetic resonance imaging (MRI) investigation in Brazil, including 37 VLE individuals (≤5 years of education). A CR score was generated combining educational attainment and vocabulary knowledge. RES indices to AD pathology were calculated using standardized residuals from linear regression models relating current cognitive performance (episodic memory or overall cognition) to amyloid beta (Aß) burden Pittsburgh compound-B ([11C]PiB-PET). RESULTS: Aß burden was lower in VLE relative to highly-educated subjects (controlling for age, sex, and Mini-Mental Status Exam [MMSE] scores) in the overall cognitively impaired sample, and in dementia subjects when the three clinically defined groups were evaluated separately. In bivariate regression analyses for the overall sample, the RES index based on a composite cognitive score was predicted by CR, socioeconomic status, and hippocampal volume (but not white matter hyperintensities or intracranial volume [ICV]); in the multivariate model, only CR retained significance (and similar results were obtained in the Aß-positive subsample). In the multivariate model for the overall sample using the RES index based on memory performance, CR, hippocampal volume, and ICV were significant predictors, whereas only CR retained significance in Aß-positive subjects. DISCUSSION: Lower CR consistently predicted less resilience to AD pathology in older adults from a low-middle income environment.

A score based on screening tests to differentiate mild cognitive impairment from subjective memory complaints.

It is not easy to differentiate patients with mild cognitive impairment (MCI) from subjective memory complainers (SMC). Assessments with screening cognitive tools are essential, particularly in primary care where most patients are seen. The objective of this study was to evaluate the diagnostic accuracy of screening cognitive tests and to propose a score derived from screening tests. Elderly subjects with memory complaints were evaluated using the Mini Mental State Examination (MMSE) and the Brief Cognitive Battery (BCB). We added two delayed recalls in the MMSE (a delayed recall and a late-delayed recall, LDR), and also a phonemic fluency test of letter P fluency (LPF). A score was created based on these tests. The diagnoses were made on the basis of clinical consensus and neuropsychological testing. Receiver operating characteristic curve analyses were used to determine area under the curve (AUC), the sensitivity and specificity for each test separately and for the final proposed score. MMSE, LDR, LPF and delayed recall of BCB scores reach statistically significant differences between groups (P=0.000, 0.03, 0.001 and 0.01, respectively). Sensitivity, specificity and AUC were MMSE: 64%, 79% and 0.75 (cut off <29); LDR: 56%, 62% and 0.62 (cut off <3); LPF: 71%, 71% and 0.71 (cut off <14); delayed recall of BCB: 56%, 82% and 0.68 (cut off <9). The proposed score reached a sensitivity of 88% and 76% and specificity of 62% and 75% for cut off over 1 and over 2, respectively. AUC were 0.81. In conclusion, a score created from screening tests is capable of discriminating MCI from SMC with moderate to good accurancy.

Thalamic alexia with agraphia.

Alexia with agraphia is defined as an acquired impairment affecting reading and writing ability. It can be associated with aphasia, but can also occur as an isolated entity. This impairment has classically been associated with a left angular gyrus lesion In the present study, we describe a case involving a patient who developed alexia with agraphia and other cognitive deficits after a thalamic hemorrhage. In addition, we discuss potential mechanisms of this cortical dysfunction syndrome caused by subcortical injury. We examined a patient who presented with alexia with agraphia and other cognitive deficits due to a hemorrhage in the left thalamus. Neuropsychological evaluation showed attention, executive function, arithmetic and memory impairments. In addition, language tests revealed severe alexia with agraphia in the absence of aphasia. Imaging studies disclosed an old thalamic hemorrhage involving the anterior, dorsomedial and pulvinar nuclei. Tractography revealed asymmetric thalamocortical radiations in the parietal region (left