Editorial: Alzheimer's Disease and the Fornix

This e-book focuses primarily on the role of the fornix as a functional, prognostic, and diagnostic marker of Alzheimer’s disease (AD), and the application of such a marker in clinical practice. Researchers have long been focused on the cortical pathology of AD, since the most important pathologic features are the senile plaques found in the cortex, and the neurofibrillary tangles and neuronal loss that start from the entorhinal cortex and the hippocampus. In addition to gray matter structures, histopathological studies indicate that the white matter is also altered in AD. The fornix is a white matter bundle that constitutes a core element of the limbic circuits, and is one of the most important anatomical structures related to memory. The fornices originate from the bilateral hippocampi, merge at the midline of the brain, again divide into the left and right side, and then into the precommissural and the postcommissural fibers, and terminate at the septal nuclei, nucleus accumbens (precommissural fornix), and hypothalamus (postcommissural fornix). These functional and anatomical features of the fornix have naturally captured researchers’ attention as possible diagnostic and prognostic markers of AD. Growing evidence indicates that the alterations seen in the fornix are potentially a good marker with which to predict future conversion from mild cognitive impairment to AD, and even from a cognitively normal state to AD. The degree of alteration is correlated with the degree of memory impairment, indicating the potential for the use of the fornix as a functional marker. Moreover, there have been attempts to stimulate the fornix to recover the cognitive function lost with AD. Our goal is to provide information about the status of current research and to facilitate further scientific and clinical advancement in this topic

F2‐02‐03: “Wecare Advisor”: a Clinical Trial of a Caregiver Focused, IPAD Administered Algorithm to Manage Behavioral Symptoms

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152585/1/alzjjalz201606386.pd

Cognitive Gains and Losses of Patients with Alzheimer's Disease During Frequent Practice

This longitudinal study of 2 patients with Alzheimer's Disease (AD), on 12 experimental tasks, was designed to identify a measure of cognitive decline in AD patients that would be sensitive to change over short periods (weeks), resistant to practice (repeated testing over a few weeks), and predictive of change over longer periods on standardized tests. During the periods of frequent testing, both patients improved on most tasks, but performance on the tasks of spelling words anc spelling pseudowords declined in the patient who deteriorated on standardized testing and remained stable in the patient who showed stable scores on standardized testing

Practice Guideline for the treatment of patients with HIV-AIDS

This guideline addresses psychiatric issues in the care of people with HIV/AIDS. Originally published in November 2000. This guideline is more than 5 years old and has not yet been updated to ensure that it reflects current knowledge and practice. In accordance with national standards, including those of the Agency for Healthcare Research and Quality’s National Guideline Clearinghouse (http://www.guideline.gov/), this guideline can no longer be assumed to be current. The April 2006 Guideline Watch associated with this guideline provides additional information that has become available since publication of the guideline, but it is not a formal update of the guideline

Surface-Based Analysis on Shape and Fractional Anisotropy of White Matter Tracts in Alzheimer's Disease

10.1371/journal.pone.0009811PLoS ONE53

Empirically Defining Trajectories of Late-Life Cognitive and Functional Decline

Background: Alzheimer’s disease (AD) is associated with variable cognitive and functional decline, and it is difficult to predict who will develop the disease and how they will progress. Objective: This exploratory study aimed to define latent classes from participants in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database who had similar growth patterns of both cognitive and functional change using Growth Mixture Modeling (GMM), identify characteristics associated with those trajectories, and develop a decision tree using clinical predictors to determine which trajectory, as determined by GMM, individuals will most likely follow. Methods: We used ADNI early mild cognitive impairment (EMCI), late MCI (LMCI), AD dementia, and healthy control (HC) participants with known amyloid-β status and follow-up assessments on the Alzheimer’s Disease Assessment Scale - Cognitive Subscale or the Functional Activities Questionnaire (FAQ) up to 24 months postbaseline. GMM defined trajectories. Classification and Regression Tree (CART) used certain baseline variables to predict likely trajectory path. Results: GMM identified three trajectory classes (C): C1 (n = 162, 13.6%) highest baseline impairment and steepest pattern of cognitive/functional decline; C3 (n = 819, 68.7%) lowest baseline impairment and minimal change on both; C2 (n = 211, 17.7%) intermediate pattern, worsening on both, but less steep than C1. C3 had fewer amyloid- or apolipoprotein-E ɛ4 (APOE4) positive and more healthy controls (HC) or EMCI cases. CART analysis identified two decision nodes using the FAQ to predict likely class with 82.3% estimated accuracy. Conclusions: Cognitive/functional change followed three trajectories with greater baseline impairment and amyloid and APOE4 positivity associated with greater progression. FAQ may predict trajectory class

Addressing the Ethical, Legal, and Social Issues Raised by Voting by Persons with Dementia

This article addresses an emerging policy problem in the United States participation in the electoral process by citizens with dementia. At present, health care professionals, family caregivers, and long-term care staff lack adequate guidance to decide whether individuals with dementia should be precluded from or assisted in casting a ballot. Voting by persons with dementia raises a series of important questions about the autonomy of individuals with dementia, the integrity of the electoral process, and the prevention of fraud. Three subsidiary issues warrant special attention: development of a method to assess capacity to vote; identification of appropriate kinds of assistance to enable persons with cognitive impairment to vote; and formulation of uniform and workable policies for voting in long-term care settings. In some instances, extrapolation from existing policies and research permits reasonable recommendations to guide policy and practice. However, in other instances, additional research is necessary

Automated Generation of Radiologic Descriptions on Brain Volume Changes From T1-Weighted MR Images: Initial Assessment of Feasibility

Purpose: To examine the feasibility and potential difficulties of automatically generating radiologic reports (RRs) to articulate the clinically important features of brain magnetic resonance (MR) images.Materials and Methods: We focused on examining brain atrophy by using magnetization-prepared rapid gradient-echo (MPRAGE) images. The technology was based on multi-atlas whole-brain segmentation that identified 283 structures, from which larger superstructures were created to represent the anatomic units most frequently used in RRs. Through two layers of data-reduction filters, based on anatomic and clinical knowledge, raw images (~10 MB) were converted to a few kilobytes of human-readable sentences. The tool was applied to images from 92 patients with memory problems, and the results were compared to RRs independently produced by three experienced radiologists. The mechanisms of disagreement were investigated to understand where machine–human interface succeeded or failed.Results: The automatically generated sentences had low sensitivity (mean: 24.5%) and precision (mean: 24.9%) values; these were significantly lower than the inter-rater sensitivity (mean: 32.7%) and precision (mean: 32.2%) of the radiologists. The causes of disagreement were divided into six error categories: mismatch of anatomic definitions (7.2 ± 9.3%), data-reduction errors (11.4 ± 3.9%), translator errors (3.1 ± 3.1%), difference in the spatial extent of used anatomic terms (8.3 ± 6.7%), segmentation quality (9.8 ± 2.0%), and threshold for sentence-triggering (60.2 ± 16.3%).Conclusion: These error mechanisms raise interesting questions about the potential of automated report generation and the quality of image reading by humans. The most significant discrepancy between the human and automatically generated RRs was caused by the sentence-triggering threshold (the degree of abnormality), which was fixed to z-score >2.0 for the automated generation, while the thresholds by radiologists varied among different anatomical structures

Celecoxib or Naproxen Treatment Does Not Benefit Depressive Symptoms in Persons Age 70 and Older: Findings From a Randomized Controlled Trial

Background: Several lines of evidence suggest that inflammatory mechanisms may be involved in the severity and progression of depression. One pathway implicated is the production of prostaglandins via the enzyme cyclooxygenase (CO

Effectiveness of Atypical Antipsychotic Drugs in Patients with Alzheimer's Disease

BACKGROUND Second-generation (atypical) antipsychotic drugs are widely used to treat psychosis, aggression, and agitation in patients with Alzheimer's disease, but their benefits are uncertain and concerns about safety have emerged. We assessed the effectiveness of atypical antipsychotic drugs in outpatients with Alzheimer's disease. METHODS In this 42-site, double-blind, placebo-controlled trial, 421 outpatients with Alzheimer's disease and psychosis, aggression, or agitation were randomly assigned to receive olanzapine (mean dose, 5.5 mg per day), quetiapine (mean dose, 56.5 mg per day), risperidone (mean dose, 1.0 mg per day), or placebo. Doses were adjusted as needed, and patients were followed for up to 36 weeks. The main outcomes were the time from initial treatment to the discontinuation of treatment for any reason and the number of patients with at least minimal improvement on the Clinical Global Impression of Change (CGIC) scale at 12 weeks. RESULTS There were no significant differences among treatments with regard to the time to the discontinuation of treatment for any reason: olanzapine (median, 8.1 weeks), quetiapine (median, 5.3 weeks), risperidone (median, 7.4 weeks), and placebo (median, 8.0 weeks) (P=0.52). The median time to the discontinuation of treatment due to a lack of efficacy favored olanzapine (22.1 weeks) and risperidone (26.7 weeks) as compared with quetiapine (9.1 weeks) and placebo (9.0 weeks) (P=0.002). The time to the discontinuation of treatment due to adverse events or intolerability favored placebo. Overall, 24% of patients who received olanzapine, 16% of patients who received quetiapine, 18% of patients who received risperidone, and 5% of patients who received placebo discontinued their assigned treatment owing to intolerability (P=0.009). No significant differences were noted among the groups with regard to improvement on the CGIC scale. Improvement was observed in 32% of patients assigned to olanzapine, 26% of patients assigned to quetiapine, 29% of patients assigned to risperidone, and 21% of patients assigned to placebo (P=0.22). CONCLUSIONS Adverse effects offset advantages in the efficacy of atypical antipsychotic drugs for the treatment of psychosis, aggression, or agitation in patients with Alzheimer's disease