Attracting New Investigators to Alzheimer’s Disease Research: Outcomes of Increased Funding and Outreach

Abstract Since 2015, the National Institute on Aging (NIA), National Institutes of Health (NIH), has experienced significant increases in funding for Alzheimer’s disease and Alzheimer’s disease-related dementias (AD/ADRD). This analysis assesses the impact of these funds on expanding the AD/ADRD workforce. NIA administered 860 awards to 695 AD/ADRD R01 awardees during fiscal year 2015–2018. Twenty-nine percent of awardees were new or early-stage investigators, while 38% were new to the AD/ADRD research field (NTF). Among these NTFs, 59% were established investigators, that is, experts with NIH funding in another discipline but new to AD/ADRD research. Awards were further analyzed to determine the focus of their research based on International Alzheimer’s Disease Research Portfolio (IADRP) categories. Forty-six percent were focused on Molecular Pathogenesis and Physiology. Other IADRP categories, including Diagnosis, Assessment, and Disease Monitoring and Translational Research and Clinical Interventions, represented 5%–15% of awards. Significantly, NTF investigators received 50%, 42%, and 70% of the total grants awarded in Population Studies, Dementia Care, and Brain Aging, respectively, suggesting that NTF investigators are filling research gaps. While these results suggest that enhanced funding is associated with recruitment of new talent, opportunities for further growth remain, particularly related to care, caregiving, and health disparities.

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Fluoxetine Protects against Dendritic Spine Loss in Middle-aged APPswe/PSEN1dE9 Double Transgenic Alzheimer’s Disease Mice

Current Alzheimer Research ◽

10.2174/1567205017666200213095419 ◽

2020 ◽

Vol 17 (1) ◽

pp. 93-103 ◽

Cited By ~ 1

Author(s):

Jing Ma ◽

Yuan Gao ◽

Wei Tang ◽

Wei Huang ◽

Yong Tang

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Dendritic Spines ◽

Dendritic Spine ◽

Early Stage ◽

Learning Ability ◽

Middle Aged ◽

Protein Levels ◽

Spine Pathology ◽

The Impact

Background: Studies have suggested that cognitive impairment in Alzheimer’s disease (AD) is associated with dendritic spine loss, especially in the hippocampus. Fluoxetine (FLX) has been shown to improve cognition in the early stage of AD and to be associated with diminishing synapse degeneration in the hippocampus. However, little is known about whether FLX affects the pathogenesis of AD in the middle-tolate stage and whether its effects are correlated with the amelioration of hippocampal dendritic dysfunction. Previously, it has been observed that FLX improves the spatial learning ability of middleaged APP/PS1 mice. Objective: In the present study, we further characterized the impact of FLX on dendritic spines in the hippocampus of middle-aged APP/PS1 mice. Results: It has been found that the numbers of dendritic spines in dentate gyrus (DG), CA1 and CA2/3 of hippocampus were significantly increased by FLX. Meanwhile, FLX effectively attenuated hyperphosphorylation of tau at Ser396 and elevated protein levels of postsynaptic density 95 (PSD-95) and synapsin-1 (SYN-1) in the hippocampus. Conclusion: These results indicated that the enhanced learning ability observed in FLX-treated middle-aged APP/PS1 mice might be associated with remarkable mitigation of hippocampal dendritic spine pathology by FLX and suggested that FLX might be explored as a new strategy for therapy of AD in the middle-to-late stage.

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Possible selves and illness: A comparison of individuals with Parkinson's disease, early-stage Alzheimer's disease, and healthy older adults

International Journal of Behavioral Development ◽

10.1080/01650250143000526 ◽

2003 ◽

Vol 27 (1) ◽

pp. 1-11 ◽

Cited By ~ 29

Author(s):

Leslie D. Frazier ◽

Victoria Cotrell ◽

Karen Hooker

Keyword(s):

Alzheimer’S Disease ◽

Older Adults ◽

Parkinson’S Disease ◽

Alzheimer's Disease ◽

Parkinson's Disease ◽

Possible Selves ◽

Early Stage ◽

Healthy Older Adults ◽

Patient Groups ◽

The Impact

This study examined how future self-representations are affected by two different chronic illnesses, one focused on cognitive losses, early-stage Alzheimer's disease (AD), and one focused on physical losses, Parkinson's disease (PD). The impact of illness on possible selves (perceptions of self in the future) was made salient by a comparison with healthy older adults in order to better understand developmental issues in later life. Findings show that although there were no differences in the total number of domains reported by the groups, specific domains were reported differently by patient groups and all domains were likely to become infused with illness. As expected, patient groups had less self-efficacy and lower outcome expectancies for their future selves, and PD patients reported less distance from their feared selves. Although these findings are intuitive, this is the first empirical effort to document the impact of illness on older adults' self-representations. Group differences are explained in terms of disease context, and the importance of possible selves and self-regulatory functions as therapeutic mechanisms for adaptation to illness are emphasised.

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Performance of healthy elderly with Alzheimer's disease at an early stage in executive function and language

European Psychiatry ◽

10.1016/s0924-9338(11)72205-2 ◽

2011 ◽

Vol 26 (S2) ◽

pp. 498-498

Author(s):

M.T. Santos ◽

G.C. Couto ◽

J.C. Achieri ◽

C.A. Júnior

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Early Stage ◽

The Elderly ◽

Screening Tests ◽

Healthy Elderly ◽

Initial Stage ◽

Significant Difference ◽

Common Causes ◽

The Impact

Dementia are increasingly prevalent in population. The most common causes of dementia is Alzheimer's disease (AD). Screening tests have been used for the premature diagnosis of Alzheimer Disease (AD), specifically in the executive functions and language, which are compromised at an initial stage. However, the necessity standardized means and validated for our middle, to show oneself a pressing subject.ObjectiveTo analyze the impact of the length of sentences in the abstraction of proverbs in the Screening Test for Alzheimer's disease with Proverbs (TRDAP), healthy elderly and with Alzheimer's disease at early stage.MethodSurvey document in the database, analyzing the responses of the elderly (abstract or concrete interpretation of proverbs), relating the length of sentences (sayings) of stage B of TRDAP with the diagnosis of Alzheimer's disease and the interference of age and schooling.ResultsHealthy older people showed greater capacity for abstraction than those with AD. There was Significant differences, in the sayings 1 (p = 0.033) and 2 (p = 0.001), corresponding to lower sentences, which did not occur with the proverb 3. As for age no verified significant difference among the healthy and only saying 3 in AD patients, however schooling differenced the healthy.ConclusionElderly with Alzheimer's disease at an initial stage have lower performance in the comprehension of ambiguous sentences, interpretation and abstraction of proverbs, corroborating with the data of the literature. The size of these sentences appears to be inversely proportional to the correctness of interpretation in elderly patients with and without AD.

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Inflammation and Insulin Resistance as Risk Factors and Potential Therapeutic Targets for Alzheimer’s Disease

Frontiers in Neuroscience ◽

10.3389/fnins.2021.653651 ◽

2021 ◽

Vol 15 ◽

Author(s):

Angeles Vinuesa ◽

Carlos Pomilio ◽

Amal Gregosa ◽

Melisa Bentivegna ◽

Jessica Presa ◽

...

Keyword(s):

Risk Factors ◽

Alzheimer’S Disease ◽

Insulin Resistance ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Brain Aging ◽

Therapeutic Targets ◽

Low Grade ◽

Increased Risk ◽

The Impact

Overnutrition and modern diets containing high proportions of saturated fat are among the major factors contributing to a low-grade state of inflammation, hyperglycemia and dyslipidemia. In the last decades, the global rise of type 2 diabetes and obesity prevalence has elicited a great interest in understanding how changes in metabolic function lead to an increased risk for premature brain aging and the development of neurodegenerative disorders such as Alzheimer’s disease (AD). Cognitive impairment and decreased neurogenic capacity could be a consequence of metabolic disturbances. In these scenarios, the interplay between inflammation and insulin resistance could represent a potential therapeutic target to prevent or ameliorate neurodegeneration and cognitive impairment. The present review aims to provide an update on the impact of metabolic stress pathways on AD with a focus on inflammation and insulin resistance as risk factors and therapeutic targets.

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Microglial TREM2 at the Intersection of Brain Aging and Alzheimer’s Disease

The Neuroscientist ◽

10.1177/10738584211040786 ◽

2021 ◽

pp. 107385842110407

Author(s):

Wenhui Qu ◽

Ling Li

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Inflammatory Responses ◽

Brain Aging ◽

Synaptic Function ◽

Loss Of Function ◽

Neuronal Function ◽

Increased Risk ◽

Health And Disease ◽

The Impact

As resident immune cells of the brain, microglia serve pivotal roles in regulating neuronal function under both physiological and pathological conditions, including aging and the most prevalent neurodegenerative disease, Alzheimer’s disease (AD). Instructed by neurons, microglia regulate synaptic function and guard brain homeostasis throughout life. Dysregulation of microglial function, however, can lead to dire consequences, including aggravated cognitive decline during aging and exacerbated neuropathology in diseases. The triggering receptor expressed on myeloid cells 2 (TREM2) is a key regulator of microglial function. Loss-of-function variants of TREM2 are associated with an increased risk of AD. TREM2 orchestrates the switch of microglial transcriptome programming that modulates microglial chemotaxis, phagocytosis, and inflammatory responses, as well as microglial regulation of synaptic function in health and disease. Intriguingly, the outcome of microglial/TREM2 function is influenced by age and the context of neuropathology. This review summarizes the rapidly growing research on TREM2 under physiological conditions and in AD, particularly highlighting the impact of TREM2 on neuronal function.

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Speech- and Language-Based Classification of Alzheimer’s Disease: A Systematic Review

Bioengineering ◽

10.3390/bioengineering9010027 ◽

2022 ◽

Vol 9 (1) ◽

pp. 27

Author(s):

Inês Vigo ◽

Luis Coelho ◽

Sara Reis

Keyword(s):

Systematic Review ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Best Practices ◽

Early Stage ◽

Low Cost ◽

Clinical Stage ◽

Invasive Procedure ◽

The Impact

Background: Alzheimer’s disease (AD) has paramount importance due to its rising prevalence, the impact on the patient and society, and the related healthcare costs. However, current diagnostic techniques are not designed for frequent mass screening, delaying therapeutic intervention and worsening prognoses. To be able to detect AD at an early stage, ideally at a pre-clinical stage, speech analysis emerges as a simple low-cost non-invasive procedure. Objectives: In this work it is our objective to do a systematic review about speech-based detection and classification of Alzheimer’s Disease with the purpose of identifying the most effective algorithms and best practices. Methods: A systematic literature search was performed from Jan 2015 up to May 2020 using ScienceDirect, PubMed and DBLP. Articles were screened by title, abstract and full text as needed. A manual complementary search among the references of the included papers was also performed. Inclusion criteria and search strategies were defined a priori. Results: We were able: to identify the main resources that can support the development of decision support systems for AD, to list speech features that are correlated with the linguistic and acoustic footprint of the disease, to recognize the data models that can provide robust results and to observe the performance indicators that were reported. Discussion: A computational system with the adequate elements combination, based on the identified best-practices, can point to a whole new diagnostic approach, leading to better insights about AD symptoms and its disease patterns, creating conditions to promote a longer life span as well as an improvement in patient quality of life. The clinically relevant results that were identified can be used to establish a reference system and help to define research guidelines for future developments.

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Assessing the Impact of Applications of Digital Health Records on Alzheimer's Disease Research

10.17226/21827 ◽

2016 ◽

Cited By ~ 1

Author(s):

◽

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Digital Health ◽

Health Records ◽

Disease Research ◽

The Impact

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Impact of Hyperhomocysteinemia and Different Dietary Interventions on Cognitive Performance in a Knock-in Mouse Model for Alzheimer’s Disease

Nutrients ◽

10.3390/nu12113248 ◽

2020 ◽

Vol 12 (11) ◽

pp. 3248

Author(s):

Hendrik Nieraad ◽

Natasja de Bruin ◽

Olga Arne ◽

Martine C. J. Hofmann ◽

Mike Schmidt ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Mouse Model ◽

Cognitive Performance ◽

Early Stage ◽

Amyloid Β ◽

Dietary Interventions ◽

Homocysteic Acid ◽

Plaque Deposition ◽

The Impact

Background: Hyperhomocysteinemia is considered a possible contributor to the complex pathology of Alzheimer’s disease (AD). For years, researchers in this field have discussed the apparent detrimental effects of the endogenous amino acid homocysteine in the brain. In this study, the roles of hyperhomocysteinemia driven by vitamin B deficiency, as well as potentially beneficial dietary interventions, were investigated in the novel AppNL-G-F knock-in mouse model for AD, simulating an early stage of the disease. Methods: Urine and serum samples were analyzed using a validated LC-MS/MS method and the impact of different experimental diets on cognitive performance was studied in a comprehensive behavioral test battery. Finally, we analyzed brain samples immunohistochemically in order to assess amyloid-β (Aβ) plaque deposition. Results: Behavioral testing data indicated subtle cognitive deficits in AppNL-G-F compared to C57BL/6J wild type mice. Elevation of homocysteine and homocysteic acid, as well as counteracting dietary interventions, mostly did not result in significant effects on learning and memory performance, nor in a modified Aβ plaque deposition in 35-week-old AppNL-G-F mice. Conclusion: Despite prominent Aβ plaque deposition, the AppNL-G-F model merely displays a very mild AD-like phenotype at the investigated age. Older AppNL-G-F mice should be tested in order to further investigate potential effects of hyperhomocysteinemia and dietary interventions.

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Behavioral Approaches to the Treatment of Alzheimer's Disease: Research Strategies

International Psychogeriatrics ◽

10.1017/s1041610296003006 ◽

1996 ◽

Vol 8 (S1) ◽

pp. 7-12 ◽

Cited By ~ 4

Author(s):

Teresa S. Radebaugh ◽

Neil Buckholtz ◽

Zaven Khachaturian

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Long Range ◽

Human Services ◽

Fiscal Year ◽

Research Strategies ◽

Senate Committee ◽

Health And Human Services ◽

Disease Research ◽

The U.S

The U.S. Senate Committee for Appropriations (for the Departments of Labor, Health and Human Services, and Education and Related Agencies), in its report of the fiscal year 1994 appropriations bill, directed the National Institute on Aging (NIA) to develop a long-range plan for taking advantage of scientific opportunities in Alzheimer's disease (AD) research.

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