Aging in the Digital Age: Using Technology to Increase the Reach of the Clinician Expert and Close the Gap Between Health Span and Life Span

Age-related cognitive impairment (ARCI) has a profound impact on individuals, families, health care systems, and societies at large. Evidence suggests that ARCI is the consequence of underlying brain pathology. Therefore, efforts to minimize the impact of ARCI and thus closing the gap between health span and life span, which has widened in recent years, requires early detection and timely deployment of targeted, personalized interventions. Access to clinical experts is limited and technology screening and assessment methods are thus appealing. However, as traditionally implemented patients were deprived of the benefit of personalized connection with a clinician, which is particularly critical for the prescription and to ensure the adherence to and ultimate success of therapeutic interventions. We present the concept of Intelligent Technology Therapy Assistant (ITA) as a scalable solution that increases the reach of clinical experts while sustaining the personal connection between each patient and their clinician. We illustrate ITA with the “Guttman Neuro Personal Trainer”®, a tele-rehabilitation platform that provides neuropsychological evaluation and care, and the Barcelona Brain Health Initiative (BBHI) multimodal intervention coaching app, a mobile-based platform that provides lifestyle coaching support in domains related to brain health. In addition, we discuss the translation of these models to a large-scale enterprise with Linus Health. To this end, we conclude with a discussion of challenges and opportunities to move the field forward.

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The impact of chronic disease and disability on the elderly

South African Journal of Physiotherapy ◽

10.4102/sajp.v55i3.567 ◽

1999 ◽

Vol 55 (3) ◽

pp. 9-14

Author(s):

C. J. Eales

Keyword(s):

Health Care ◽

Chronic Disease ◽

Chronic Diseases ◽

Health Care Systems ◽

The Elderly ◽

Therapeutic Interventions ◽

Elderly Persons ◽

Care Systems ◽

And Function ◽

The Impact

Health care systems for elderly people should aim to delay the onset of illness, reducing the final period of infirmity and illness to the shortest possible time. The most effective way to achieve this is by health education and preventative medicine to maintain mobility and function. Changes in life style even in late life may result in improved health, effectively decreasing the incidence of chronic diseases associated with advancing age. This paper presents the problems experienced by elderly persons with chronic diseases and disabilities with indications for meaningful therapeutic interventions.

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Molecular mechanisms of life- and health-span extension: role of calorie restriction and exercise intervention

Applied Physiology Nutrition and Metabolism ◽

10.1139/h07-085 ◽

2007 ◽

Vol 32 (5) ◽

pp. 954-966 ◽

Cited By ~ 49

Author(s):

Christy S. Carter ◽

Tim Hofer ◽

Arnold Y. Seo ◽

Christian Leeuwenburgh

Keyword(s):

Life Span ◽

Calorie Restriction ◽

Aging Process ◽

Molecular Mechanisms ◽

Geriatric Medicine ◽

Functional Decline ◽

Intervention Strategies ◽

Health Span ◽

Structural Deterioration ◽

Age Related

The aging process results in a gradual and progressive structural deterioration of biomolecular and cellular compartments and is associated with many pathological conditions, including cardiovascular disease, stroke, Alzheimer’s disease, osteoporosis, sarcopenia, and liver dysfunction. Concomitantly, each of these conditions is associated with progressive functional decline, loss of independence, and ultimately disability. Because disabled individuals require care in outpatient or home care settings, and in light of the social, emotional, and fiscal burden associated with caring for an ever-increasing elderly population, research in geriatric medicine has recently focused on the biological mechanisms that are involved in the progression towards functional decline and disability to better design treatment and intervention strategies. Although not completely understood, the mechanisms underlying the aging process may partly involve inflammatory processes, oxidative damage, mitochondrial dysfunction, and apoptotic tissue degeneration. These hypotheses are based on epidemiological evidence and data from animal models of aging, as well as interventional studies. Findings from these studies have identified possible strategies to decrease the incidence of age-related diseases and delay the aging process. For example, lifelong exercise is known to extend mean life-span, whereas calorie restriction (CR) increases both mean and maximum life-span in a variety of species. Optimal application of these intervention strategies in the elderly may positively affect health-related outcomes and possibly longevity. Therefore, the scope of this article is to (i) provide an interpretation of various theories of aging from a “health-span” perspective; (ii) describe interventional testing in animals (CR and exercise); and (iii) provide a translational interpretation of these data.

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Contributions of Aging to Cerebral Small Vessel Disease

Annual Review of Physiology ◽

10.1146/annurev-physiol-021119-034338 ◽

2020 ◽

Vol 82 (1) ◽

pp. 275-295 ◽

Cited By ~ 2

Author(s):

T. Michael De Silva ◽

Frank M. Faraci

Keyword(s):

Recent Progress ◽

Small Vessel Disease ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

Brain Health ◽

Vessel Disease ◽

Age Related ◽

The Face ◽

Basic Biology ◽

The Impact

Cerebral small vessel disease (SVD) is characterized by changes in the pial and parenchymal microcirculations. SVD produces reductions in cerebral blood flow and impaired blood-brain barrier function, which are leading contributors to age-related reductions in brain health. End-organ effects are diverse, resulting in both cognitive and noncognitive deficits. Underlying phenotypes and mechanisms are multifactorial, with no specific treatments at this time. Despite consequences that are already considerable, the impact of SVD is predicted to increase substantially with the growing aging population. In the face of this health challenge, the basic biology, pathogenesis, and determinants of SVD are poorly defined. This review summarizes recent progress and concepts in this area, highlighting key findings and some major unanswered questions. We focus on phenotypes and mechanisms that underlie microvascular aging, the greatest risk factor for cerebrovascular disease and its subsequent effects.

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HIV as a Cause of Immune Activation and Immunosenescence

Mediators of Inflammation ◽

10.1155/2017/6825493 ◽

2017 ◽

Vol 2017 ◽

pp. 1-16 ◽

Cited By ~ 40

Author(s):

T. Sokoya ◽

H. C. Steel ◽

M. Nieuwoudt ◽

T. M. Rossouw

Keyword(s):

Immune Activation ◽

Large Scale ◽

Antiretroviral Treatment ◽

Treatment Guidelines ◽

Hiv Treatment ◽

Therapeutic Interventions ◽

Adjunctive Treatment ◽

Systemic Immune Activation ◽

Proinflammatory Mediators ◽

Age Related

Systemic immune activation has emerged as an essential component of the immunopathogenesis of HIV. It not only leads to faster disease progression, but also to accelerated decline of overall immune competence. HIV-associated immune activation is characterized by an increase in proinflammatory mediators, dysfunctional T regulatory cells, and a pattern of T-cell-senescent phenotypes similar to those seen in the elderly. These changes predispose HIV-infected persons to comorbid conditions that have been linked to immunosenescence and inflamm-ageing, such as atherosclerosis and cardiovascular disease, neurodegeneration, and cancer. In the antiretroviral treatment era, development of such non-AIDS-defining, age-related comorbidities is a major cause of morbidity and mortality. Treatment strategies aimed at curtailing persistent immune activation and inflammation may help prevent the development of these conditions. At present, the most effective strategy appears to be early antiretroviral treatment initiation. No other treatment interventions have been found effective in large-scale clinical trials, and no adjunctive treatment is currently recommended in international HIV treatment guidelines. This article reviews the role of systemic immune activation in the immunopathogenesis of HIV infection, its causes and the clinical implications linked to immunosenescence in adults, and the therapeutic interventions that have been investigated.

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ASPREE SUB-STUDIES

Innovation in Aging ◽

10.1093/geroni/igz038.2361 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

pp. S634-S634

Author(s):

Robyn L Woods ◽

John J McNeil ◽

Anne Murray

Keyword(s):

Older Persons ◽

Large Scale ◽

Social Issues ◽

Brain Mri ◽

Age Related Macular Degeneration ◽

Age Related ◽

Aging Health ◽

Cerebral Microhemorrhages ◽

Areas Of Interest ◽

The Impact

Abstract To maximize opportunities provided by a large-scale clinical trial, we established sub-studies during the ASPREE trial to investigate specific areas of interest to the health of older persons. A biobank now stores multiple aliquots of blood, urine or saliva collected from >15,000 healthy ASPREE participants across the US and Australia, most at baseline (pre-randomization) and/or after 3 years post- randomization. Other sub-studies included ALSOP (ASPREE Longitudinal Study of Older Persons; sets of questionnaires administered every 2 years focused on medical or social issues) and neuroimaging projects with brain MRI and retinal vascular imaging to investigate anatomical changes linked with cognitive or cerebrovascular outcomes. Further sub-studies addressed the impact of aspirin on cerebral microhemorrhages, age-related macular degeneration, age-related hearing loss, severe sepsis, and falls and fractures. Biomarker analyses underway include plasma androgens in older women and DNA sequencing of the cohort to investigate contributions of genomics to aging health and disease.

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Speech Recognition Across the Life Span: Longitudinal Changes From Middle-Age to Older Adults

American Journal of Audiology ◽

10.1044/2015_aja-14-0052 ◽

2015 ◽

Vol 24 (2) ◽

pp. 84-87 ◽

Cited By ~ 10

Author(s):

Judy R. Dubno

Keyword(s):

Speech Recognition ◽

Word Recognition ◽

Life Span ◽

Pure Tone ◽

Large Scale ◽

Mixed Model ◽

Middle Age ◽

Age Related ◽

And Gender ◽

Age Related Hearing Loss

Purpose The purpose of this article is to provide an overview of evidence of age-related declines in speech recognition in middle age to older adulthood; to review contributions of pure-tone thresholds, age, and gender; and to report preliminary results from a longitudinal study. Method Pure-tone thresholds and word recognition in quiet and babble are being measured in a large sample of adults yearly or every 2 to 3 years. Analyses included >16,000 audiograms and speech recognition scores from >1,200 adults whose ages ranged from the 40s to the 90s. A multivariable generalized linear repeated mixed model assessed changes in thresholds and speech recognition over time. Results Word recognition in quiet declined significantly while controlling for threshold increases, and declines appeared to accelerate near ages 65 to 70 years. Scores for men were poorer than those for women even after controlling for gender differences in thresholds, but rates of decline did not differ by gender. Smaller declines in key word recognition in babble were observed, and declines appeared to accelerate near ages 75 to 80 years. Conclusions Additional evidence is needed from large-scale longitudinal cohort studies to determine rates of change of auditory function across the life span. These studies can identify associations with modifiable risk factors and potential mechanisms to reduce, to prevent, or to delay the onset of age-related hearing loss.

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Age-related differences in structural and functional prefrontal networks during a logical reasoning task

10.1101/854224 ◽

2019 ◽

Cited By ~ 2

Author(s):

Maryam Ziaei ◽

Mohammad Reza Bonyadi ◽

David C. Reutens

Keyword(s):

Older Adults ◽

Large Scale ◽

Inferior Frontal Gyrus ◽

Functional Results ◽

Logical Reasoning ◽

Anterior Cingulate ◽

Belief Bias ◽

Reasoning Task ◽

Age Related ◽

The Impact

AbstractIn logical reasoning, difficulties in inhibition of currently-held beliefs may lead to unwarranted conclusions, known as belief bias. Aging is associated with difficulties in inhibitory control, which may lead to deficits in inhibition of currently-held beliefs. No study to date, however, has investigated the underlying neural substrates of age-related differences in logical reasoning and the impact of belief load. The aim of the present study was to delineate age differences in brain activity during a syllogistic logical reasoning task while the believability load of logical inferences was manipulated. Twenty-nine, healthy, younger and thirty, healthy, older adults (males and females) completed a functional magnetic resonance imaging experiment in which they were asked to determine the logical validity of conclusions. Unlike younger adults, older adults engaged a large-scale network including anterior cingulate cortex (ACC) and inferior frontal gyrus (IFG) during conclusion stage. Our functional connectivity results suggest that while older adults engaged the ACC network to overcome their intuitive responses for believable inferences, the IFG network contributed to higher control over responses during both believable and unbelievable conditions. Our functional results were further supported by structure-function-behavior analyses indicating the importance of cingulum bundle and uncinate fasciculus integrity in rejection of believable statements. These novel findings lend evidence for age-related differences in belief bias, with potentially important implications for decision making where currently-held beliefs and given assumptions are in conflict.

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Polygenetic-Risk Scores Related to Crystallin Metabolism Are Associated with Age-Related Cataract Formation and Interact with Hyperglycemia, Hypertension, Western-Style Diet, and Na Intake

Nutrients ◽

10.3390/nu12113534 ◽

2020 ◽

Vol 12 (11) ◽

pp. 3534

Author(s):

Donghyun Jee ◽

Suna Kang ◽

ShaoKai Huang ◽

Sunmin Park

Keyword(s):

Large Scale ◽

Crystalline Lens ◽

Positive Association ◽

The Elderly ◽

Risk Scores ◽

Nucleotide Polymorphisms ◽

Multifactor Dimensionality Reduction Analysis ◽

Coffee Intake ◽

Age Related ◽

The Impact

Age-related cataract (ARC) development is associated with loss of crystalline lens transparency related to interactions between genetic and environmental factors. We hypothesized that polygenetic risk scores (PRS) of the selected genetic variants among the ARC-related genes might reveal significant genetic impacts on ARC risk, and the PRS might have gene–gene and gene–lifestyle interactions. We examined the hypothesis in 1972 and 39,095 subjects aged ≥50 years with and without ARC, respectively, in a large-scale hospital-based cohort study conducted from 2004 to 2013. Single nucleotide polymorphisms (SNPs) of the genes related to ARC risk were identified, and polygenetic risk scores (PRS) were generated based on the results of a generalized multifactor dimensionality reduction analysis. Lifestyle interactions with PRS were evaluated. The PRS derived from the best model included the following six SNPs related to crystallin metabolism: ULK4_rs1417380362, CRYAB_rs2070894, ACCN1_rs55785344, SSTR2_rs879419608, PTN_rs322348, and ICA1_rs200053781. The risk of ARC in the high-PRS group was 2.47-fold higher than in the low-PRS group after adjusting for confounders. Age, blood pressure, and glycemia interacted with PRS to influence the risk of ARC: the incidence of ARC was much higher in the elderly (≥65 years) and individuals with hypertension or hyperglycemia. The impact of PRS on ARC risk was greatest in middle-aged individuals with hypertension or hyperglycemia. Na, coffee, and a Western-style diet intake also interacted with PRS to influence ARC risk. ARC risk was higher in the high-PRS group than in the low-PRS group, and high Na intake, Western-style diet, and low coffee intake elevated its risk. In conclusion, ARC risk had a positive association with PRS related to crystallin metabolism. The genetic impact was greatest among those with high Na intake or hypertension. These results can be applied to precision nutrition interventions to prevent ARC.

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A large-scale multi-institutional study evaluating prognostic aspects of positive ascites cytology and effects of therapeutic interventions in epithelial ovarian cancer

Scientific Reports ◽

10.1038/s41598-021-93718-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Masato Yoshihara ◽

Ryo Emoto ◽

Kazuhisa Kitami ◽

Shohei Iyoshi ◽

Kaname Uno ◽

...

Keyword(s):

Ovarian Cancer ◽

Large Scale ◽

Negative Impact ◽

Early Stage ◽

Stage Iv ◽

Therapeutic Interventions ◽

Limited Information ◽

Mucinous Histology ◽

Staging Surgery ◽

The Impact

AbstractPositive ascites cytology is a strong prognostic factor in patients with early-stage ovarian cancer (OvCa). However, limited information is currently available on the impact of positive ascites cytology on patient prognoses under each clinical background. We herein investigated the comprehensive impact of positive ascites cytology on patients with epithelial OvCa and the effectiveness of additional therapeutic interventions, including complete staging surgery and chemotherapy. Among 4730 patients with malignant ovarian neoplasms, retrospectively identified in multiple institutions, 1906 with epithelial OvCa were included. In the investigation of its effects on clinical factors using a multivariate analysis, positive ascites cytology correlated with a poor prognosis. Positive ascites cytology had a significantly worse prognosis than those with negative cytology in all subgroups except for patients with stage IV tumors and a mucinous histology. Chemotherapy may be effective in reducing the negative impact of positive ascites cytology on the prognosis of patients in terms of progression-free and overall survivals, while complete staging surgery did not improve the prognosis of patients with positive ascites cytology. Collectively, our findings suggested that positive ascites cytology had a negative impact on the prognosis of patients with epithelial OvCa, but not those with stage IV tumors or a mucinous histology.

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Prognostic Aspects of Positive Ascites Cytology and Effects of Therapeutic Interventions in Epithelial Ovarian Cancer: a Large-scale Multi-institutional Study

10.21203/rs.3.rs-431054/v1 ◽

2021 ◽

Author(s):

Masato Yoshihara ◽

Ryo Emoto ◽

Kazuhisa Kitami ◽

Shohei Iyoshi ◽

Kaname Uno ◽

...

Keyword(s):

Ovarian Cancer ◽

Large Scale ◽

Negative Impact ◽

Early Stage ◽

Stage Iv ◽

Therapeutic Interventions ◽

Limited Information ◽

Mucinous Histology ◽

Staging Surgery ◽

The Impact

Abstract Positive ascites cytology is a strong prognostic factor in patients with early-stage ovarian cancer (OvCa). However, limited information is currently available on the impact of positive ascites cytology on patient prognoses under each clinical background. We herein investigated the comprehensive impact of positive ascites cytology on patients with epithelial OvCa and the effectiveness of additional therapeutic interventions, including complete staging surgery and chemotherapy. Among 4,730 patients with malignant ovarian neoplasms, retrospectively identified in multiple institutions, 1,906 with epithelial OvCa were included. In the investigation of its effects on clinical factors using a multivariate analysis, positive ascitic cytology correlated with a poor prognosis. Positive ascites cytology had a significantly worse prognosis than those with negative cytology in all subgroups except for patients with stage IV tumors and a mucinous histology. Chemotherapy may be effective in reducing the negative impact of positive ascites cytology on the prognosis of patients in terms of progression-free and overall survivals, while complete staging surgery did not improve the prognosis of patients with positive ascites cytology. Collectively, our findings suggested that positive ascites cytology had a negative impact on the prognosis of patients with epithelial OvCa, but not those with stage IV tumors or a mucinous histology.

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