The problem of multiple adjustments in the assessment of minimal clinically important differences.

Introduction: Anthropometric, demographic, genetic, and clinical features may affect cognitive, behavioral, and functional decline, while clinical trials seldom consider minimal clinically important differences (MCIDs) in their analyses.

Methods: MCIDs were reviewed taking into account features that may affect cognitive, behavioral, or functional decline in clinical trials of new disease-modifying therapies.

Results: The higher the number of comparisons of different confounders in statistical analyses, the lower values will be significant.

Anthropometric and Demographic Features Affect the Interpretation of Cerebrospinal Fluid Biomarkers in Patients with Different Dementia Syndromes and Cognitively Healthy Adults.

Clinical distinction between dementia with Lewy bodies (DLB) and late-onset Alzheimer's disease (AD) is difficult, while several features might affect the analyses of biomarkers. This study aimed to verify associations of anthropometric and demographic features with cerebrospinal fluid biomarkers, their ratios, and restructured traditional regression formulas in patients with DLB and AD, as well as in cognitively healthy controls. Consecutive outpatients with DLB were paired with outpatients with AD according to sex, dementia stage, and cognitive status, and with controls according to sex and age to investigate associations of sex, age, dementia duration, total sleep time, body mass index, alcohol use, smoking, sanitation, and APOE-ε4 alleles on the measurement of cerebrospinal fluid α-synuclein, biomarker ratios, and restructured traditional regression formulas involving amyloid-β (Aβ,Aβ,Aβ), tau, and phospho-tau Thr.

Assessing Independence in Activities of Daily Living and Quality of Life in Patients with Dementia with Lewy Bodies.

Knowledge of performance in activities of daily living and quality of life is important for management decisions and research endpoints. The use of harmonized scales is essential for objective assessment of both caregivers and patients with dementia with Lewy bodies. Functionality and quality of life are more impaired in dementia with Lewy bodies than in Alzheimer's disease, mostly due to higher prevalence of behavioral symptoms and motor manifestations in dementia with Lewy bodies.

Shedding Light on the Effects of Blood Pressure on Cognitive Decline and Dementia Risk by Way of Neurobiological Evidence.

Midlife cerebrovascular risk factors increase risk of late life cognitive impairment and dementia, while their presence in patients with dementia may lead to cognitive improvement or stabilization in late life. Defining the best measure of blood pressure (BP) to be associated with cognitive decline remains debatable, also due to possible bidirectionality. BP variability, pulse pressure, systolic and diastolic BP have been associated with cognitive status, dementia risk and Alzheimer's disease biomarkers.

Pitfalls and biases in neuroepidemiological studies of COVID-19 and the nervous system: a critical appraisal of the current evidence and future directions.

Background: Neurological manifestations frequently occur in individuals with COVID-19, manifesting during the acute phase, persisting beyond the resolution of acute symptoms, and appearing days or weeks after the initial onset of COVID-19 symptoms. However, predicting the incidence, course, and outcome of these neurological manifestations at the individual patient level remains challenging. Biases in study design and limitations in data collection may contribute to the inconsistency and limited validity of the reported findings.

Looking Behind the Curtain: Patient Stratification According to Genetic or Demographic Factors May Yield Unexpected Results in Studies of Neurodegenerative Diseases.

Amyloid-PET studies of neurodegenerative diseases may yield inconclusive findings due to lacking stratification according to genetic or demographic variants. APOEɛ4 alleles are the major variants to increase disease susceptibility and cause earlier onset and more behavioral features in patients with late-onset Alzheimer's disease, but have no linear effects on cognitive or functional decline; thus, sample stratification according to APOEɛ4 carrier status may be the best option. Interactions among APOEɛ4 alleles, sex, and age on amyloid-β deposition may reveal even more innovative findings with sufficiently large samples, suggesting variable genomic effects of cognitive reserve, sex differences, and cerebrovascular risk on neurodegeneration.

Differential associations of clinical features with cerebrospinal fluid biomarkers in dementia with Lewy bodies and Alzheimer's disease.

Aim: To explore associations of cerebrospinal fluid biomarkers of neurodegeneration and amyloidosis with caregiver burden, cognition and functionality in dementia with Lewy bodies (DLB) paired with late-onset Alzheimer's disease (AD) and healthy older people.

Methods: Consecutive outpatients with DLB were matched with outpatients with AD according to sex, cognitive scores and dementia stage, and with cognitively healthy controls according to age and sex to investigate associations of cerebrospinal fluid amyloid-β (Aβ,Aβ,Aβ), tau, phospho-tau Thr, ubiquitin, α-synuclein and neurofilament light with caregiver burden, functionality, reverse digit span, a clock drawing test, Mini-Mental State Examination (MMSE) and Severe MMSE, adjusted for sex, age, education, dementia duration and APOE-ε4 alleles.

Results: Overall, 27 patients with DLB (78.

The Advisory Group on Risk Evidence Education for Dementia: Multidisciplinary and Open to All.

The brain changes of Alzheimer's disease and other degenerative dementias begin long before cognitive dysfunction develops, and in people with subtle cognitive complaints, clinicians often struggle to predict who will develop dementia. The public increasingly sees benefits to accessing dementia risk evidence (DRE) such as biomarkers, predictive algorithms, and genetic information, particularly as this information moves from research to demonstrated usefulness in guiding diagnosis and clinical management. For example, the knowledge that one has high levels of amyloid in the brain may lead one to seek amyloid reducing medications, plan for disability, or engage in health promoting behaviors to fight cognitive decline.

Psychosis as a Treatment Target in Dementia: A Roadmap for Designing Interventions.

Psychotic phenomena are among the most severe and disruptive symptoms of dementias and appear in 30% to 50% of patients. They are associated with a worse evolution and great suffering to patients and caregivers. Their current treatments obtain limited results and are not free of adverse effects, which are sometimes serious.

Vascular cognitive impairment and dementia: An early career researcher perspective.

The field of vascular contributions to cognitive impairment and dementia (VCID) is evolving rapidly. Research in VCID encompasses topics aiming to understand, prevent, and treat the detrimental effects of vascular disease burden in the human brain. In this perspective piece, early career researchers (ECRs) in the field provide an overview of VCID, discuss past and present efforts, and highlight priorities for future research.

Pharmacogenetic Analyses of Therapeutic Effects of Lipophilic Statins on Cognitive and Functional Changes in Alzheimer's Disease.

Background: Pharmacogenetic effects of statins on clinical changes in Alzheimer's disease (AD) could be mediated by epistatic interactions among relevant genetic variants involved in cholesterol metabolism.

Objective: To investigate associations of HMGCR (rs3846662), NR1H2 (rs2695121), or CETP (rs5882&rs708272) with cognitive and functional changes in AD, with stratification according to APOEɛ4 carrier status and lipid-lowering treatment with lipophilic statins.

Methods: Consecutive outpatients with late-onset AD were screened with cognitive tests, while caregivers scored functionality and global ratings, with prospective neurotranslational associations documented for one year.

APOE ε4 Carrier Status as Mediator of Effects of Psychotropic Drugs on Clinical Changes in Patients With Alzheimer's Disease.

Objective: Neuropsychiatric syndromes have been associated with memory dysfunction and risk of and earlier onset of dementia, but how psychotropic drugs affect clinical changes in Alzheimer's disease is not entirely clear. This study aimed to assess the prospective effects of psychotropic drugs on cognitive and functional changes in Alzheimer's disease according to APOE ε4 carrier status.

Methods: The study included consecutive outpatients with late-onset Alzheimer's disease (N=193) and examined score variations at 1 year on the following tests: Clinical Dementia Rating sum of boxes, Mini-Mental State Examination, Severe Mini-Mental State Examination (SMMSE), Brazilian version of the Zarit Caregiver Burden Interview, Index of Independence in Activities of Daily Living, and Lawton's Instrumental Activities of Daily Living Scale.

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.

Associations of Neuropsychiatric Features with Cerebrospinal Fluid Biomarkers of Amyloidogenesis and Neurodegeneration in Dementia with Lewy Bodies Compared with Alzheimer's Disease and Cognitively Healthy People.

Background: Behavioral features may reflect proteinopathies predicting pathophysiology in neurodegenerative diseases.

Objective: We aimed to investigate associations of cerebrospinal fluid biomarkers of amyloidogenesis and neurodegeneration with neuropsychiatric features in dementia with Lewy bodies (DLB) compared with late-onset Alzheimer's disease (AD) and cognitively healthy people.

Methods: Consecutive outpatients with DLB were paired with outpatients with AD according to sex, dementia stage, and cognitive scores, and with cognitively healthy controls according to sex and age to investigate associations of cerebrospinal fluid amyloid-β (Aβ)42, Aβ40, Aβ38, total tau, phospho-tau Thr181, α-synuclein, ubiquitin, and neurofilament light with neuropsychiatric features according to APOEɛ4 carrier status.

Swallowing in behavioral variant frontotemporal dementia.

Background: Swallowing and feeding problems may occur with the progression of behavioral variant frontotemporal dementia (bvFTD) and can impair the anticipatory and oral preparatory phases of swallowing.

Objective: To characterize swallowing problems and the feeding situation of patients with bvFTD and to correlate the swallowing problems with functionality, executive functions, cognitive and behavioral features.

Methods: Consecutive outpatients with bvFTD in mild, moderate and severe dementia stages were recruited along with their caregivers.

The impact of SARS-CoV-2 in dementia across Latin America: A call for an urgent regional plan and coordinated response.

The SARS-CoV-2 global pandemic will disproportionately impact countries with weak economies and vulnerable populations including people with dementia. Latin American and Caribbean countries (LACs) are burdened with unstable economic development, fragile health systems, massive economic disparities, and a high prevalence of dementia. Here, we underscore the selective impact of SARS-CoV-2 on dementia among LACs, the specific strain on health systems devoted to dementia, and the subsequent effect of increasing inequalities among those with dementia in the region.

LOW-DOSE NALTREXONE REVERSES FACIAL MECHANICAL ALLODYNIA IN A RAT MODEL OF TRIGEMINAL NEURALGIA.

Trigeminal neuralgia (TN) is a type of neuropathic pain characterized by intense pain; although anticonvulsants are used as an option to relieve pain, adverse side effects can decrease patient adherence. In this context, a low dose of naltrexone is effective in relieving pain in other pain conditions. Thus, the objective of the present study was to evaluate the analgesic effect of low-dose naltrexone on facial mechanical allodynia in a rat model of TN, as well as its effect(s) on biomarkers in the central nervous system (tumor necrosis factor-alpha, brain-derived neurotrophic factor [BDNF], interleukin [IL]-10, and toll-like receptor-4).

Selected LDLR and APOE Polymorphisms Affect Cognitive and Functional Response to Lipophilic Statins in Alzheimer's Disease.

Effects of statins over clinical changes in Alzheimer's disease (AD) are usually non-significant, but epistatic interactions between genetic variants involved in cholesterol metabolism could be important for such effects. We aimed to investigate whether LDLR single-nucleotide polymorphisms rs11669576 (LDLR8), rs5930 (LDLR10), and rs5925 (LDLR13) are associated with cognitive and functional changes in AD, while also considering APOE haplotypes and lipid-lowering treatment with lipophilic statins for stratification. Consecutive outpatients with late-onset AD were screened with cognitive tests, while caregivers scored functionality and caregiver burden, with prospective neurotranslational correlations documented for 1 year.

Neuropsychiatric feature profiles of patients with Lewy body dementia.

Objective: Differential diagnosis between Parkinson's disease (PD) dementia and dementia with Lewy bodies (DLB) is difficult due to common features, whereas management decisions and research endpoints depend upon knowledge of dementia severity. We aimed to assess risk factors for age at dementia onset, as well as which neuropsychiatric features are associated with pharmacotherapy and signs and symptoms of Lewy body dementia.

Patients And Methods: Patients with PD dementia or DLB were evaluated for age at disease onset, education, sanitation, anthropometric measures, alcohol use, smoking, history of infections or head trauma with unconsciousness, family history of neurodegenerative diseases, functional independence, cognition, behavior, motor features, caregiver burden and pharmacotherapy.