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

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

Effect of the WeCareAdvisor™ on family caregiver outcomes in dementia: a pilot randomized controlled trial

Abstract Background Behavioral and psychological symptoms of dementia (BPSD) are universal and associated with multiple negative outcomes. This pilot randomized controlled trial (RCT) evaluated the effect of using the WeCareAdvisor, an innovative web-based tool developed to enable family caregivers to assess, manage, and track BPSD. Methods This RCT enrolled 57 dementia family caregivers from community and clinical settings in Ann Arbor, Michigan and Baltimore, Maryland. Participants were randomly assigned to immediate use of the WeCareAdvisor tool (WCA, n = 27) or a Waitlist control group (n = 30) that received the tool after a one-month waiting period. Outcomes for the caregiver and the person they were caring for were assessed at baseline (T0) and one-month followup for both the WCA (T1) and Waitlist control (T2) groups. Results Caregiver mean age was 65.9 ± 14.0 years old. About half (49%) were spouses. Baseline characteristics were comparable between groups except for mean caregiver confidence which was higher in the control group (WCA 35.0 ± 10.0 vs. Waitlist control 39.7 ± 6.9, p = 0.04). There were no significant differences between the WCA and control groups in characteristics of the person with dementia. After their one-month of tool use (T1), WCA caregivers showed significant within group improvement in caregiver distress (− 6.08 ± 6.31 points, t = − 4.82, p < 0.0001) and behavioral frequency (− 3.60 ± 5.05, t = − 3.56, p = 0.002), severity (− 3.24 ± 3.87, t = − 4.19, p = 0.0003) and total behavioral score (− 6.80 ± 10.73, t = − 3.17, p = 004). In the same timeframe, Waitlist control caregivers showed a significant decrease in confidence (− 6.40 ± 10.30, t = − 3.40, p = 0.002). The WCA group showed greater improvement in distress compared to the Waitlist group (T0-T1; t = − 2.49, p = 0.02), which remained significant after adjusting for site and baseline distress. There were no significant between-group differences in caregiver confidence or other secondary outcomes. After their one month of tool use (T2), the Waitlist group also showed significant improvement in caregiver distress (− 3.72 ± 7.53, t = − 2.66, p = 0.013), stress (− 0.41 ± 1.02, t = − 2.19, p = 0.037), confidence (4.38 ± 5.17, t = 4.56, p < 0.0001), burden (− 2.76 ± 7.26, t = − 2.05, p = 0.05), negative communication (− 1.48 ± 2.96, t = − 2.70, p = 0.012) and behavioral frequency (− 1.86 ± 4.58, t = − 2.19, p = 0.037); distress remained significant after adjustment. Conclusions In this pilot RCT, WCA use resulted in a significant decrease in caregiver distress. Future research will identify whether longer use of WCA can impact other caregiver and behavioral outcomes. Trial registration Clinicaltrials.gov identifier NCT02420535 (Date of registry: 4/20/2015, prior to the start of the clinical trial).https://deepblue.lib.umich.edu/bitstream/2027.42/143536/1/12877_2018_Article_801.pd

Home is where the future is: The BrightFocus Foundation consensus panel on dementia care

IntroductionA national consensus panel was convened to develop recommendations on future directions for home‐based dementia care (HBDC).MethodsThe panel summarized advantages and challenges of shifting to HBDC as the nexus of care and developed consensus‐based recommendations.ResultsThe panel developed five core recommendations: (1) HBDC should be considered the nexus of new dementia models, from diagnosis to end of life in dementia; (2) new payment models are needed to support HBDC and reward integration of care; (3) a diverse new workforce that spans the care continuum should be prepared urgently; (4) new technologies to promote communication, monitoring/safety, and symptoms management must be tested, integrated, and deployed; and (5) targeted dissemination efforts for HBDC must be employed.DiscussionHBDC represents a promising paradigm shift to improve care for those living with dementia and their family caregivers: these recommendations provide a framework to chart a course forward for HBDC.HighlightsFive core BrightFocus Foundation panel recommendations:Home‐based dementia care should be considered the nexus of new long‐term care models.New payment models are needed to stimulate, reward, and support home care practices.A skilled new workforce spanning long‐term care needs to be developed and equipped.New technologies to promote best practices must be tested, integrated, and deployed.Value propositions and improved public health communication are needed.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152597/1/alzjjalz201710006.pd

Metabolic Changes Associated With Second-Generation Antipsychotic Use in Alzheimer’s Disease Patients: The CATIE-AD Study

The second-generation antipsychotics are associated with metabolic abnormalities in patients with schizophrenia. Elderly patients with Alzheimer’s disease are frequently treated with these antipsychotics but there is little data available on their metabolic effects

Imaging of Glial Cell Activation and White Matter Integrity in Brains of Active and Recently Retired National Football League Players

Importance: Microglia, the resident immune cells of the central nervous system, play an important role in the brain\u27s response to injury and neurodegenerative processes. It has been proposed that prolonged microglial activation occurs after single and repeated traumatic brain injury, possibly through sports-related concussive and subconcussive injuries. Limited in vivo brain imaging studies months to years after individuals experience a single moderate to severe traumatic brain injury suggest widespread persistent microglial activation, but there has been little study of persistent glial cell activity in brains of athletes with sports-related traumatic brain injury. Objective: To measure translocator protein 18 kDa (TSPO), a marker of activated glial cell response, in a cohort of National Football League (NFL) players and control participants, and to report measures of white matter integrity. Design, Setting, and Participants: This cross-sectional, case-control study included young active (n = 4) or former (n = 10) NFL players recruited from across the United States, and 16 age-, sex-, highest educational level-, and body mass index-matched control participants. This study was conducted at an academic research institution in Baltimore, Maryland, from January 29, 2015, to February 18, 2016. Main Outcomes and Measures: Positron emission tomography-based regional measures of TSPO using [11C]DPA-713, diffusion tensor imaging measures of regional white matter integrity, regional volumes on structural magnetic resonance imaging, and neuropsychological performance. Results: The mean (SD) ages of the 14 NFL participants and 16 control participants were 31.3 (6.1) years and 27.6 (4.9) years, respectively. Players reported a mean (SD) of 7.0 (6.4) years (range, 1-21 years) since the last self-reported concussion. Using [11C]DPA-713 positron emission tomographic data from 12 active or former NFL players and 11 matched control participants, the NFL players showed higher total distribution volume in 8 of the 12 brain regions examined (P \u3c .004). We also observed limited change in white matter fractional anisotropy and mean diffusivity in 13 players compared with 15 control participants. In contrast, these young players did not differ from control participants in regional brain volumes or in neuropsychological performance. Conclusions and Relevance: The results suggest that localized brain injury and repair, indicated by higher TSPO signal and white matter changes, may be associated with NFL play. Further study is needed to confirm these findings and to determine whether TSPO signal and white matter changes in young NFL athletes are related to later onset of neuropsychiatric symptoms