Aging Alzheimer Research Articles

Caring for the Caregivers: An Alzheimer Disease Research Center Call to Action.

Currently, over 16 million dementia caregivers in the US provide over 18 billion hours of care. As the number of persons living with dementia increases, so too will the number of family caregivers. Given the projected steady growth in caregivers and their health-related needs in caring for persons living with Alzheimer disease and related dementias, several initiatives are underway that focus on caregivers. One overlooked mechanism to meet caregiver needs is the National Institute on Aging's Alzheimer's Disease Research Centers (ADRCs). Through secondary analysis, we present a picture of dementia caregiving from the National Alzheimer's Coordinating Center's database and discuss a call to action for ADRCs to engage caregivers and further support the mission of the ADRC to advance the field of dementia research.

Association between educational attainment and amyloid deposition across the spectrum from normal cognition to dementia: neuroimaging evidence for protection and compensation

The brain mechanisms underlying the effect of intellectual enrichment may evolve along the normal aging Alzheimer's disease (AD) cognitive spectrum and may include both protective and compensatory mechanisms. We assessed the association between early intellectual enrichment (education, years) and average cortical florbetapir standardized uptake value ratio as well as performed voxel-wise analyses in a total of 140 participants, including cognitively normal older adults, mild cognitive impairment (MCI), and AD patients. Higher education was associated with lower cortical florbetapir positron emission tomography (florbetapir-PET) uptake, notably in the frontal lobe in normal older adults, but with higher uptake in frontal, temporal, and parietal regions in MCI after controlling for global cognitive status. No association was found in AD. In MCI, we observed an increased fluorodeoxyglucose positron emission tomography (FDG-PET) uptake with education within the regions of higher florbetapir-PET uptake, suggesting a compensatory increase. Early intellectual enrichment may be associated with protection and compensation for amyloid beta (Aβ) deposition later in life, before the onset of dementia. Previous investigations have been controversial as regard to the effects of intellectual enrichment variables on Aβ deposition; the present findings call for approaches aiming to evaluate mechanisms of resilience across disease stages.

Neurofibrillary Tangle Stage and the Rate of Progression of Alzheimer Symptoms

The heterogeneity of rate of clinical progression among patients with Alzheimer disease leads to difficulty in providing clinical counseling and diminishes the power of clinical trials using disease-modifying agents. To gain a better understanding of the factors that affect the natural history of progression in Alzheimer disease for the purpose of improving both clinical care and clinical trial design. A longitudinal cohort study of aging from 2005 to 2014 in the National Alzheimer Coordinating Center. Clinical evaluation of the participants was conducted in 31 National Institute on Aging's Alzheimer Disease Centers. Nine hundred eighty-four participants in the National Alzheimer Coordinating Center cohort study who died and underwent autopsy and met inclusion and exclusion criteria. We sought to model the possibility that knowledge of neurofibrillary tangle burden in the presence of moderate or frequent plaques would add to the ability to predict clinical rate of progression during the ensuing 2 to 3 years. We examined the National Alzheimer Coordinating Center autopsy data to evaluate the effect of different neurofibrillary tangle stages on the rates of progression on several standard clinical instruments: the Clinical Dementia Rating Scale sum of boxes, a verbal memory test (logical memory), and a controlled oral word association task (vegetable naming), implementing a reverse-time longitudinal modeling approach in conjunction with latent class estimation to adjust for unmeasured sources of heterogeneity. Several correlations between clinical variables and neurocognitive performance suggest a basis for heterogeneity: Higher education level was associated with lower Clinical Dementia Rating Scale sum of boxes (β = -0.19; P < .001), and frequent vs moderate neuritic plaques were associated with higher Clinical Dementia Rating Scale sum of boxes (β = 1.64; P < .001) and lower logical memory score (β = -1.07; P = .005). The rate of change of the clinical and cognitive scores varied depending on Braak stage, when adjusting for plaques, age of death, sex, education, and APOE genotype. For example, comparing high vs low Braak stage with other variables fixed, the logical memory score decreased a substantial 0.38 additional units per year (95% CI, -0.70 to -0.06; P = .02). Using these data, we estimate that a 300-participant clinical trial with end point of a 20% improvement in slope in rate of change of Clinical Dementia Rating Scale sum of boxes has 89% power when all participants in the trial are from the high Braak stage, compared with 29% power if Braak stage had not used for eligibility. We found that knowledge of neurofibrillary tangle stage, modeled as the sort of information that could be available from tau positron-emission tomography scans and its use to determine eligibility to a trial, could dramatically improve the power of clinical trials and equivalently reduce the required sample sizes of clinical trials.

Searching for Primary Predictors of Conversion from Mild Cognitive Impairment to Alzheimer's Disease: A Multivariate Follow-Up Study.

Recent proposals of diagnostic criteria within the healthy aging-Alzheimer's disease (AD) continuum stressed the role of biomarker information. More importantly, such information might be critical to predict those mild cognitive impairment (MCI) patients at a higher risk of conversion to AD. Usually, follow-up studies utilize a reduced number of potential markers although the conversion phenomenon may be deemed as multifactorial in essence. In addition, not only biological but also cognitive markers may play an important role. Considering this background, we investigated the role of cognitive reserve, cognitive performance in neuropsychological testing, hippocampal volumes, APOE genotype, and magnetoencephalography power sources to predict the conversion to AD in a sample of 33 MCI patients. MCIs were followed up during a 2-year period and divided into two subgroups according to their outcome: The "stable" MCI group (sMCI, 21 subjects) and the "progressive" MCI group (pMCI, 12 subjects). Baseline multifactorial information was submitted to a hierarchical logistic regression analysis to build a predictive model of conversion to AD. Results indicated that the combination of left hippocampal volume, occipital cortex theta power, and clock drawing copy subtest scores predicted conversion to AD with a 100% of sensitivity and 94.7% of specificity. According to these results it might be suggested that anatomical, cognitive, and neurophysiological markers may be considered as "first order" predictors of progression to AD, while APOE or cognitive reserve proxies might play a more secondary role.

Help Alzheimer's Patients and Caregivers With Online Resources

Help Alzheimer's Patients and Caregivers With Online Resources

MEG Delta Mapping Along the Healthy Aging-Alzheimer's Disease Continuum: Diagnostic Implications

New diagnostic criteria for Alzheimer's disease (AD) stress the role of in vivo biomarkers. Neurophysiological markers are usually not considered as such criteria, although theoretical and practical reasons would justify them. In order to assess the value of neurophysiology as an AD biomarker, whole-head magnetoencephalographic (MEG) resting state recordings were obtained from 35 AD patients, 23 mild cognitive impairment (MCI) patients, and 24 healthy controls. The AD group was further split into two groups differing in severity according to the GDS/FAST criteria. A Minimum Norm Estimation procedure was utilized to estimate the cortical origin of slow brain oscillatory activity in the delta band (2-4 Hz). Eight regions of interest (ROIs) discriminated between AD patients and controls. Delta current density (DCD) in all ROIs showed a significant negative correlation with cognitive status (p < 0.001). DCD values in posterior parietal, occipital, prerolandic, and precuneus cortices distinguished reliably between MCI patients, AD patients with different severity scores, and controls. Importantly, an increase of DCD in right parietal cortex and precuneus indexed the transition from MCI to mild dementia and from mild to more severe dementia. MEG delta mapping might be a serious candidate for a "neural degeneration" marker of AD reflecting dysfunctional synaptic transmission. More importantly, the localization of DCD values is in line with functional imaging markers of AD. However, MEG delta mapping is a totally non-invasive technique that directly measures neural activity. We propose that individuals with enhanced DCD in posterior parietal and precuneus cortices are at risk of progression to full dementia.

The effects of a dementia nurse care manager on improving caregiver outcomes outcomes.

Iowa's Administration on Aging's Alzheimer's Disease Demonstration Grant to the States was a project to implement and evaluate a nurse care management model of service delivery for persons with dementia or care recipient and their family caregiver that was integrated with the case management system. The goal of the nursing service delivery model was to maintain persons with dementia safely in their homes, by connecting them with appropriate services and providing support to the care recipient and caregivers. Outcomes measures were evaluated over time. This article defines the role of dementia nurse care management and shares the results of the outcomes measurements. The evaluation showed that caregivers assisted by nurse care managements were more likely to show improvement in their stress levels, endurance potential, and well-being. This improvement was consistent over time.

Encyclopedia of Alzheimer's disease: with directories of research, treatment and care facilities

The first and largest section of this encyclopedia offers such entries as disease pathology (genetic influences, disease stages and diagnosis), brain anatomy and physiology (cellular and biochemical cholinergic changes, the nervous system and plaque formation), disease process (stages and subtypes of Alzheimer's, coexisting illnesses and associated disorders), research and treatment (therapeutic options, drug efficacy and clinical trials), care and caregivers (memory aids, caregiver burdens and respite care) and government programs (laws, research centers, and federal insurance programs). Section Two is a directory, by state, of the National Institute of Aging's Alzheimer's Disease Centers, and government, clinical and university affiliated treatment and research centers. Section Three is a directory of home care providers and assisted living, adult day care and long-term residential facilities, noting location, special accommodations, certifications, number of beds, accreditations, insurance information, and URL if available.

Comment on the Utility of the ADDGS Evaluation for Policy and Practice

SUMMARY This article comments on the policy and practice implications of findings from research on the Administration on Aging's Alzheimer's Disease Demonstration Grants to States program. Evaluation of fifteen state grantees has produced extensive knowledge about diverse patterns of service use, factors related to service use and satisfaction, mechanisms for developing home- and community-based services appropriate for various cultural groups, and ways to adapt established programs and integrate new services into existing systems and networks. Utilizing the general lessons from the Alzheimer's Demonstration program evaluation in program and policy development in aging is discussed.

Clinical global impressions in Alzheimer's clinical trials.

This article reviews the history of Clinical Global Impressions of Change (CGIC) instruments, their use and limitations in clinical trials of Alzheimer's disease, and the development of the National Institute on Aging's Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change Scale (ADCS-CGIC). Originally, CGICs were simple and unstructured instruments that asked a clinician to rate change over the duration of a clinical trial. The method, however, failed to consistently detect treatment effects, leading to the development of more structured and subsequently validated approaches, such as the Clinician Interview-Based Impression Scale (CIBI) and the ADCS-CGIC. Both are currently used in clinical trials. The implications and importance of choosing an appropriate global rating are discussed.