Psychoanalysis and Neuroscience: The Bridge Between Mind and Brain.

In 1895 in the Project for a Scientific Psychology, Freud tried to integrate psychology and neurology in order to develop a neuroscientific psychology. Since 1880, Freud made no distinction between psychology and physiology. His papers from the end of the 1880s to 1890 were very clear on this scientific overlap: as with many of his contemporaries, Freud thought about psychology essentially as the physiology of the brain.

New Perspective for Non-invasive Brain Stimulation Site Selection in Mild Cognitive Impairment: Based on Meta- and Functional Connectivity Analyses.

Background: Non-invasive brain stimulation (NIBS) has been widely used to treat mild cognitive impairment (MCI). However, there exists no consensus on the best stimulation sites.

Objective: To explore potential stimulation locations for NIBS treatment in patients with MCI, combining meta- and resting state functional connectivity (rsFC) analyses.

Unified Staging System for Lewy Body Disorders: Clinicopathologic Correlations and Comparison to Braak Staging.

This study was designed to correlate clinical findings with the extent of pathologic a-synuclein (aSyn) in the brain using the Unified Staging System for Lewy Body disorders (USSLB). Data from 280 cases from the Arizona Study of Aging and Neurodegenerative Disorders are presented. Each case had a complete USSLB staging and at least 1 full research clinical assessment, including subspecialty neurologist-administered movement and cognitive evaluation.

Sex Moderates Amyloid and Apolipoprotein ε4 Effects on Default Mode Network Connectivity at Rest.

Women are more likely to have Alzheimer's disease (AD) and decline more rapidly once diagnosed despite greater verbal memory early in the disease compared to men-an advantage that has been termed "memory reserve." Resting state functional MRI (fMRI) investigations demonstrate interactions between sex and AD risk factors in default mode network (DMN) connectivity, a network of brain regions showing progressive dysfunction in AD. Separate work suggests connectivity of left prefrontal cortex (PFC) may correlate with more general cognitive reserve in healthy aging.

The "rights" of precision drug development for Alzheimer's disease.

There is a high rate of failure in Alzheimer's disease (AD) drug development with 99% of trials showing no drug-placebo difference. This low rate of success delays new treatments for patients and discourages investment in AD drug development. Studies across drug development programs in multiple disorders have identified important strategies for decreasing the risk and increasing the likelihood of success in drug development programs.

Souvenaid in the management of mild cognitive impairment: an expert consensus opinion.

Background: Mild cognitive impairment (MCI) among an aging global population is a growing challenge for healthcare providers and payers. In many cases, MCI is an ominous portent for dementia. Early and accurate diagnosis of MCI provides a window of opportunity to improve the outcomes using a personalized care plan including lifestyle modifications to reduce the impact of modifiable risk factors (for example, blood pressure control and increased physical activity), cognitive training, dietary advice, and nutritional support.

Training in improvisation techniques helps reduce caregiver burden and depression: Innovative Practice.

This study measured outcomes of a novel pilot program designed to teach improvisation skills to caregivers of family members with dementia. Fifteen caregivers completed questionnaires measuring changes in their perception of burden (Zarit Burden Interview), depression (Beck Depression Inventory), their cared-for person's neuropsychiatric symptoms (Neuropsychiatric Inventory Questionnaire), and experiences related to caregiving. Caregivers' depressive symptoms and sense of burden significantly decreased after completing the six-week program.

Awareness of Psychiatric Symptoms in a Mixed Clinical Sample of Older Adults.

Objective: This study examined the neuropsychological correlates and impact on caregiver distress of reduced awareness of mood symptoms in patients with suspected neurodegenerative disease.

Method: Records from a clinical sample of older adults were examined (N = 940).

Results: More than one-third of patient and caregiver ratings of mood symptoms did not agree (comparing patient and caregiver self-report measures); 27.

Advances in Management of Neuropsychiatric Syndromes in Neurodegenerative Diseases.

Purpose Of Review: Neuropsychiatric syndromes (NPS) are common in neurodegenerative disorders (NDD). This review describes the role of NPS in the diagnosis of NDD, criteria for the diagnosis of NPS, management of NPS, and agents in clinical trials for NPS.

Recent Findings: NPS play an increasingly important role in the diagnosis of NDD.

Further analyses of the safety of verubecestat in the phase 3 EPOCH trial of mild-to-moderate Alzheimer's disease.

Background: Verubecestat, a BACE1 inhibitor that reduces Aβ levels in the cerebrospinal fluid of humans, was not effective in a phase 3 trial (EPOCH) of mild-to-moderate AD and was associated with adverse events. To assist in the development of BACE1 inhibitors, we report detailed safety findings from EPOCH.

Methods: EPOCH was a randomized, double-blind, placebo-controlled 78-week trial evaluating verubecestat 12 mg and 40 mg in participants with mild-to-moderate AD diagnosed clinically.

Alzheimer's disease drug development pipeline: 2019.

Introduction: Alzheimer's disease (AD) has few available treatments, and there is a high rate of failure in AD drug development programs. Study of the AD drug development pipeline can provide insight into the evolution of drug development and how best to optimize development practices.

Methods: We reviewed clinicaltrials.

Performing Sparse Regularization and Dimension Reduction Simultaneously in Multimodal Data Fusion.

Collecting multiple modalities of neuroimaging data on the same subject is increasingly becoming the norm in clinical practice and research. Fusing multiple modalities to find related patterns is a challenge in neuroimaging analysis. Canonical correlation analysis (CCA) is commonly used as a symmetric data fusion technique to find related patterns among multiple modalities.

The Pathology of Rapid Cognitive Decline in Clinically Diagnosed Alzheimer's Disease.

Background: Variable rate of cognitive decline among individuals with Alzheimer's disease (AD) is an important consideration for disease management, but risk factors for rapid cognitive decline (RCD) are without consensus.

Objective: To investigate demographic, clinical, and pathological differences between RCD and normal rates of cognitive decline (NCD) in AD.

Methods: Neuropsychology test and autopsy data was pulled from the National Alzheimer's Coordinating Center database from individuals with a clinical diagnosis of AD.

A 24-week double-blind placebo-controlled study of the efficacy and safety of the AMPA modulator S47445 in patients with mild to moderate Alzheimer's disease and depressive symptoms.

Introduction: S47445 is a novel positive allosteric modulator of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptors that may emerge as a favorable candidate for the symptomatic treatment of cognitive and depressive disorders in patients suffering from Alzheimer's disease (AD) of mild to moderate severity and with depressive symptoms.

Methods: For this double-blind, placebo-controlled 24-week phase II trial, 520 outpatients aged between 55 and 85 years, with probable AD at mild to moderate stages (a Mini-Mental State Examination score of 24-15 inclusive) and exhibiting depressive symptoms (Cornell Scale for Depression in Dementia [CSDD] ≥ 8) were recruited in twelve countries and randomized to 3 doses of S47445 (5-15-50 mg) or placebo. The primary end point was the change from baseline in the 11-item Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) total score at week 24.

Faster cognitive decline in dementia due to Alzheimer disease with clinically undiagnosed Lewy body disease.

Background: Neuropathology has demonstrated a high rate of comorbid pathology in dementia due to Alzheimer's disease (ADD). The most common major comorbidity is Lewy body disease (LBD), either as dementia with Lewy bodies (AD-DLB) or Alzheimer's disease with Lewy bodies (AD-LB), the latter representing subjects with ADD and LBD not meeting neuropathological distribution and density thresholds for DLB. Although it has been established that ADD subjects with undifferentiated LBD have a more rapid cognitive decline than those with ADD alone, it is still unknown whether AD-LB subjects, who represent the majority of LBD and approximately one-third of all those with ADD, have a different clinical course.

Does informant-based reporting of cognitive symptoms predict amyloid positivity on positron emission tomography?

Introduction: Researchers are searching for clinical instruments to predict amyloid positivity for disease classification. Informant-based reports could detect disease status. This study compares subjective memory complaints captured by informant-based reports between positron emission tomography (PET)-positive and PET-negative patients and hypothesizes that amyloid PET positivity associates with increased informant-based cognitive complaints.

Enrichment factors for clinical trials in mild-to-moderate Alzheimer's disease.

Introduction: Heterogeneity of outcomes in Alzheimer's disease (AD) clinical trials necessitates large sample sizes and contributes to study failures. This analysis determined whether mild-to-moderate AD populations could be enriched for cognitive decline based on apolipoprotein () ε4 genotype, family history of AD, and amyloid abnormalities.

Methods: Modeling estimated the number of randomized patients needed to detect a 2-point treatment difference on the AD Assessment Scale-Cognitive subscale using placebo data from three randomized, double-blind trials (ClinicalTrials.

Associations between Comorbid TDP-43, Lewy Body Pathology, and Neuropsychiatric Symptoms in Alzheimer's Disease.

More than half of the patients with Alzheimer's disease (AD) have comorbidities including TDP-43 and Lewy bodies, which are also associated with frontotemporal lobar degeneration and dementia with Lewy bodies, respectively. These comorbidities may help explain the overlapping neuropsychiatric symptoms between AD and other dementias. Data on 221 AD patients with Neuropsychiatric Inventory-Questionnaire were obtained from the National Alzheimer's Coordinating Center.

Regional neuropathology distribution and verbal fluency impairments in Parkinson's disease.

Background: Verbal fluency deficits are common in patients with Parkinson's disease. The association of these impairments with regional neuropathological changes is unexplored.

Objectives: Determine if patients with verbal fluency impairments have greater neuropathological burden in frontal, temporal, and limbic regions and if Lewy bodies or neurofibrillary tangles were associated with verbal fluency impairments.

Tau immunotherapies for Alzheimer's disease.

Introduction: Alzheimer's dementia (AD) is the most common form of dementia in the World. Pathologically, it is characterized by extracellular β-amyloid plaques and intraneuronal neurofibrillary tangles (NFTs). The latter is composed of irregular, pathological forms of the tau protein.

Anti-Tau Trials for Alzheimer's Disease: A Report from the EU/US/CTAD Task Force.

Efforts to develop effective disease-modifying treatments for Alzheimer's disease (AD) have mostly targeted the amyloid β (Aβ) protein; however, there has recently been increased interest in other targets including phosphorylated tau and other forms of tau. Aggregated tau appears to spread in a characteristic pattern throughout the brain and is thought to drive neurodegeneration. Both neuropathological and imaging studies indicate that tau first appears in the entorhinal cortex and then spreads to the neocortex.

Robust Motion Regression of Resting-State Data Using a Convolutional Neural Network Model.

Resting-state functional magnetic resonance imaging (rs-fMRI) based on the blood-oxygen-level-dependent (BOLD) signal has been widely used in healthy individuals and patients to investigate brain functions when the subjects are in a resting or task-negative state. Head motion considerably confounds the interpretation of rs-fMRI data. Nuisance regression is commonly used to reduce motion-related artifacts with six motion parameters estimated from rigid-body realignment as regressors.

Effect of STN DBS on vesicular monoamine transporter 2 and glucose metabolism in Parkinson's disease.

Introduction: Deep brain stimulation (DBS) is an established treatment for Parkinson's Disease (PD). Despite the improvement of motor symptoms in most patients by sub-thalamic nucleus (STN) DBS and its widespread use, the neurobiological mechanisms are not completely understood. The objective of the present study was to elucidate the effects of subthalamic nucleus (STN) DBS in PD on the dopamine system and neural circuitry, employing high-resolution positron emission tomography (PET) imaging.