Achieving and Maintaining Cognitive Vitality With Aging

This report contains the summary results of a workshop held at Canyon Ranch Health Resort in Tucson, Arizona. Physicians and scientists shed light on the process of cognitive aging. They review current scientific and clinical knowledge of normal human cognitive aging, the biological mechanisms that underlie this process, and risk factors associated with mental decline. They make recommendations for lifestyle changes and outline a research agenda for the development of new therapies to prevent mental decline and maintain cognitive vitality

Beyond amyloid: a diverse portfolio of novel drug discovery programs for Alzheimer's disease and related dementias

Although the molecular mechanisms underlying the pathogenesis of Alzheimer's disease and other related neurodegenerative diseases remain unclear, accumulation of misfolded proteins, neuroinflammation, mitochondrial dysfunction and perturbed calcium homeostasis have been identified as key events leading to neuronal loss during neurodegeneration. Evidence for 'druggable' targets for each of these key mechanisms was presented by the Alzheimer's Drug Discovery Foundation-funded investigators at the 12th International Conference on Alzheimer's Drug Discovery, Jersey City, NJ, 26-27 September 2011 http://www.worldeventsforum.com/addf/addrugdiscovery

A diverse portfolio of novel drug discovery efforts for Alzheimer's disease: Meeting report from the 11th International Conference on Alzheimer's Drug Discovery, 27-28 September 2010, Jersey City, NJ, USA

While Alzheimer's disease researchers continue to debate the underlying cause(s) of the disease, most agree that a diverse, multi-target approach to treatment will be necessary. To this end, the Alzheimer's Drug Discovery Foundation (ADDF) recently hosted the 11th International Conference on Alzheimer's Drug Discovery to highlight the array of exciting efforts from the ADDF's funded investigators

Analysis of Episodes of Care in Medicare Beneficiaries Newly Diagnosed with Alzheimer’s Disease

OBJECTIVES: To study transitions between healthcare settings and quantify the cost burdens associated with different combinations of transitions during a 6-month period before initial Alzheimer’s disease (AD) diagnosis so as to investigate how using an episode-of-care approach to payment for specific disease states might apply in AD. DESIGN: A retrospective observational cohort study. SETTING: United States. PARTICIPANTS: A random sample of 8,995 individuals aged 65 to 100 with a diagnosis of AD (International Classification of Diseases, Ninth Revision, Clinical Modification code 331.0) were identified from the Medicare database between January 1, 2011, and June 30, 2014. This analysis identified individuals with AD diagnosed in inpatient (18%), skilled nursing facility (SNF) (1%), hospice (4%), and home and outpatient (77%) settings and analyzed episodes that began in the index setting (defined as the care setting in which the individual was first diagnosed with AD). MEASUREMENTS: Study outcomes included number of transitions between settings, primary discharge diagnoses, and total all-cause healthcare costs during the 6 months after the AD diagnosis. RESULTS: The average numbers of transitions between care settings were 2.8 originating from an inpatient setting, 2.4 from a SNF, 0.3 from a hospice setting and 0.7 from a home or outpatient setting during 6 months post-AD diagnosis. The overall cost burden during the 6 months after AD diagnosis (including costs incurred at the index setting) was high for individuals diagnosed in a nonambulatory setting (mean $41,468). Individuals diagnosed in an ambulatory setting incurred only$12,597 in costs during the same period. CONCLUSION: Episodes of care can be defined and studied in individuals with AD. An episode-of-care approach to payment could encourage providers to use the continuum of care needed for quality medical management in AD more efficiently

Relationships between plasma biomarkers, tau PET, FDG PET, and volumetric MRI in mild to moderate Alzheimers disease patients.

INTRODUCTION: The A/T/N (amyloid/tau/neurodegeneration) framework provides a biological basis for Alzheimers disease (AD) diagnosis and can encompass additional changes such as inflammation (I). A spectrum of T/N/I imaging and plasma biomarkers was acquired in a phase 2 clinical trial of rasagiline in mild to moderate AD patients. We evaluated these to understand biomarker distributions and relationships within this population. METHODS: Plasma biomarkers of pTau-181, neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), other inflammation-related proteins, imaging measures including fluorodeoxyglucose (FDG) positron emission tomography (PET), flortaucipir PET, and volumetric magnetic resonance imaging (MRI), and cognitive endpoints were analyzed to assess characteristics and relationships for the overall population (N = 47 at baseline and N = 21 for longitudinal cognitive comparisons) and within age-decade subgroups (57-69, 70-79, 80-90 years). RESULTS: Data demonstrate wide clinical and biomarker heterogeneity in this population influenced by age and sex. Plasma pTau-181 and GFAP correlate with tau PET, most strongly in left inferior temporal cortex (p = 0.0002, p = 0.0006, respectively). In regions beyond temporal cortex, tau PET uptake decreased with age for the same pTau-181 or GFAP concentrations. FDG PET and brain volumes correlate with tau PET in numerous regions (such as inferior temporal: p = 0.0007, p = 0.00001, respectively). NfL, GFAP, and all imaging modalities correlate with baseline MMSE; subsequent MMSE decline is predicted by baseline parahippocampal and lateral temporal tau PET (p = 0.0007) and volume (p = 0.0006). Lateral temporal FDG PET (p = 0.006) and volume (p = 0.0001) are most strongly associated with subsequent ADAS-cog decline. NfL correlates with FDG PET and baseline MMSE but not tau PET. Inflammation biomarkers are intercorrelated but correlated with other biomarkers in only the youngest group. DISCUSSION: Associations between plasma biomarkers, imaging biomarkers, and cognitive status observed in this study provide insight into relationships among biological processes in mild to moderate AD. Findings show the potential to characterize AD patients regarding likely tau pathology, neurodegeneration, prospective clinical decline, and the importance of covariates such as age. HIGHLIGHTS: Plasma pTau-181 and GFAP correlated with regional and global tau PET in mild to moderate AD.NfL correlated with FDG PET and cognitive endpoints but not plasma pTau-181 or tau PET.Volume and FDG PET showed strong relationships to tau PET, one another, and cognitive status.Temporal volumes most strongly predicted decline in both MMSE and ADAS-cog.Volume and plasma biomarkers can enrich for elevated tau PET with age a significant covariate

Economic Burden, Mortality, and Institutionalization in Patients Newly Diagnosed with Alzheimer’s Disease

Background: Current information is scarce regarding comorbid conditions, treatment, survival, institutionalization, and health care utilization for Alzheimer’s disease (AD) patients. Objectives: Compare all-cause mortality, rate of institutionalization, and economic burden between treated and untreated newly-diagnosed AD patients. Methods: Patients aged 65–100 years with ≥1 primary or ≥2 secondary AD diagnoses (ICD-9-CM:331.0] with continuous medical and pharmacy benefits for ≥12 months pre-index and ≥6 months post-index date (first AD diagnosis date) were identified from Medicare fee-for-service claims 01JAN2011–30JUN2014. Patients with AD treatment claims or AD/ADrelated dementia diagnosis during the pre-index period were excluded. Patients were assigned to treated and untreated cohorts based on AD treatment received post-index date. Total 8,995 newly-diagnosed AD patients were identified; 4,037 (44.8%) were assigned to the treated cohort. Time-to-death and institutionalization were assessed using Cox regression. To compare health care costs and utilizations, 1 : 1 propensity score matching (PSM) was used. Results: Untreated patients were older (83.85 versus 81.44 years; p \u3c 0.0001), with more severe comorbidities (mean Charlson comorbidity index: 3.54 versus 3.22; p \u3c 0.0001). After covariate adjustment, treated patients were less likely to die (hazard ratio[HR] = 0.69; p \u3c 0.0001) and were associated with 20% lower risk of institutionalization (HR = 0.801; p = 0.0003). After PSM, treated AD patients were less likely to have hospice visits (3.25% versus 9.45%; p \u3c 0.0001), and incurred lower annual all-cause costs ($25,828 versus$30,110; p = 0.0162). Conclusion: After controlling for comorbidities, treated AD patients have better survival, lower institutionalization, and sometimes fewer resource utilizations, suggesting that treatment and improved care management could be beneficial for newly-diagnosed AD patients from economic and clinical perspectives

O5‐08‐01: Trends In Racial And Ethnic Differences In Dementia Prevalence Rates And Disease Awareness

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153266/1/alzjjalz2019064876.pd

A call for transparent reporting to optimize the predictive value of preclinical research

The US National Institute of Neurological Disorders and Stroke convened major stakeholders in June 2012 to discuss how to improve the methodological reporting of animal studies in grant applications and publications. The main workshop recommendation is that at a minimum studies should report on sample-size estimation, whether and how animals were randomized, whether investigators were blind to the treatment, and the handling of data. We recognize that achieving a meaningful improvement in the quality of reporting will require a concerted effort by investigators, reviewers, funding agencies and journal editors. Requiring better reporting of animal studies will raise awareness of the importance of rigorous study design to accelerate scientific progress