Harvey Cohen

Overview:

Dr. Cohen's research program includes clinical research relating to aspects of the pathways to functional decline and reilience with aging, geriatric assessment, and cancer and anemia in the elderly.

Pathways to functional decline are being explored through the NIA funded Claude Pepper Older Americans Independence Center, and includes studies of the contributions of age related physiologic change, in particular changes in inflammatory parameters, comorbid diseases and conditions, environment, genetics, and the interactionas among them. Data are derived from several current studies as well as previously collected data sets from the Established Populations for Epidemiologic Studies of the Elderly (EPESE), National Long Term Care Survey, and the Chinese Longevity Study (with Dr. Zeng Yi). Previous work has demonstrated the important contributions of age related inflammation and coagulation activation to functional status. He is Co-PI of the Pepper Center Physical Performance Across the LifeSpan (PALS) study, which is a longitudinal cohort study of community dwelling adults from age 30-90+and includes functional measures and biomarkers on inflammation and metabolism.
 
Geriatric assessment approaches have been studied in a number of randomized and controlled studies and work is now concentrating on the application of Comprehensive Geriatric Assessment tools to the evaluation and treatment of elderly patients with cancer. This is an extension and continuation of a long standing interest in geriatric oncology. Previous studies have elucidated age-related patterns of disease presentation, treatment approaches, clinical trials, survivorship, quality of life, impact of comrobidities and functional outcomes. Dr. Cohen was co-chair, and now member of the Cancer in the Older Adult Committee of the Alliance for Clinical Trials in Oncology (ALLIANCE). A number of active studies and ongoing data bases aree being utilized to address these questions.


Anemia in the older adult is being addressed through an NIA funded U01 consortium (Dr. Cohen Co-PI). the current main study is an observational study followed by a pragmatic treatment trial for anemia in older adults with CHF, in collaboration with the Cardiovascular Research Network (CVRN) of the Health services research network (HSRN) 

Positions:

Professor of Medicine

Medicine, Geriatrics
School of Medicine

Walter Kempner Distinguished Professor of Medicine, in the School of Medicine

Medicine, Geriatrics
School of Medicine

Emeritus Director, Center for the Study of Aging & Human Development

Center for the Study of Aging and Human Development
School of Medicine

Faculty Research Scholar of DuPRI's Center for Population Health & Aging

Center for Population Health & Aging
Institutes and Provost's Academic Units

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 1965

State University of New York, Brooklyn

Grants:

Quantifying the genomic consequences of chronic social stress for accelerated aging

Administered By
Institutes and Provost's Academic Units
Awarded By
National Institutes of Health
Role
Advisor
Start Date
End Date

IPA-Rick Sloane

Administered By
Center for the Study of Aging and Human Development
Awarded By
Durham Veterans Affairs Medical Center
Role
Principal Investigator
Start Date
End Date

Mentoring Intervention Development in Fall and Fracture Prevention

Administered By
Medicine, Geriatrics
Awarded By
National Institutes of Health
Role
Advisor
Start Date
End Date

Cognitive Changes and Brain Connectivity in Age-Related Macular Degeneration

Administered By
Center for the Study of Aging and Human Development
Awarded By
National Institutes of Health
Role
Co Investigator
Start Date
End Date

PACTTE-Partnership for Anemia: Clinical and Translational Trials in the Elderly

Administered By
Duke Clinical Research Institute
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Publications:

Tryptophan Metabolism and Neurodegeneration: Longitudinal Associations of Kynurenine Pathway Metabolites with Cognitive Performance and Plasma Alzheimer's Disease and Related Dementias Biomarkers in the Duke Physical Performance Across the LifeSpan Study.

BACKGROUND: The kynurenine pathway (KP) comprises a family of tryptophan-derived metabolites that some studies have reported are associated with poorer cognitive performance and an increased risk of Alzheimer's disease and related dementias (ADRD). OBJECTIVE: The objective of this study was to determine the associations of plasma KP metabolites (kynurenine [KYN], kynurenic acid [KA], and tryptophan [TRP]) with a panel of plasma ADRD biomarkers (Aβ42/ β40 ratio, pTau-181, glial fibrillary acidic protein [GFAP], and neurofilament light [NfL]) and cognitive performance in a subset of older adults drawn from the Duke Physical Performance Across the LifeSpan (PALS) study. METHODS: The Montreal Cognitive Assessment (MoCA) was used to assess cognitive performance. We used multivariate multiple regression to evaluate associations of the KYN/TRP and KA/KYN ratios with MoCA score and plasma ADRD biomarkers at baseline and over two years (n = 301; Age = 74.8±8.7). RESULTS: Over two years, an increasing KYN/TRP ratio was associated with increasing plasma concentrations of plasma p-Tau181 (β= 6.151; 95% CI [0.29, 12.01]; p = 0.040), GFAP (β= 11.12; 95% CI [1.73, 20.51]; p = 0.020), and NfL (β= 11.13; 95% CI [2.745, 19.52]; p = 0.009), but not MoCA score or the Aβ42/Aβ40 ratio. There were no significant associations of KA/KYN with MoCA score or plasma ADRD biomarkers. CONCLUSION: Our findings provide evidence that greater concentrations of KP metabolites are associated longitudinally over two years with greater biomarker evidence of neurofibrillary tau pathology (pTau-181), neuroinflammation (GFAP), and neurodegeneration (NfL), suggesting that dysregulated KP metabolism may play a role in ADRD pathogenesis.
Authors
Parker, DC; Kraus, WE; Whitson, HE; Kraus, VB; Smith, PJ; Cohen, HJ; Pieper, CF; Faldowski, RA; Hall, KS; Huebner, JL; Ilkayeva, OR; Bain, JR; Newby, LK; Huffman, KM
MLA Citation
URI
https://scholars.duke.edu/individual/pub1560530
PMID
36565121
Source
pubmed
Published In
J Alzheimers Dis
Published Date
DOI
10.3233/JAD-220906

Low-Intensity Adjuvant Chemotherapy for Breast Cancer in Older Women: Results From the Prospective Multicenter HOPE Trial.

<h4>Purpose</h4>Older women with high-risk early breast cancer (EBC) benefit from adjuvant chemotherapy, but their treatment is frequently complicated by toxic side effects, resulting in dose reductions and delays. This makes it challenging for oncologists to maintain a relative dose intensity (RDI) ≥ 85%, as recommended for optimal curative-intent treatment. Understanding which women are at risk of receiving suboptimal RDI may inform treatment discussions and guide early, targeted supportive care or geriatric comanagement interventions.<h4>Methods</h4>This was a prespecified secondary analysis of the HOPE trial, which enrolled women age ≥ 65 years with EBC initiating neoadjuvant or adjuvant chemotherapy. RDI was calculated as the ratio of delivered to planned chemotherapy dose intensity. The primary outcome was low RDI, defined as RDI < 85%. Multivariable logistic regression with stepwise selection was used to evaluate the association between baseline variables (demographic, clinical, and geriatric assessment) and low RDI. Survival probability was estimated using the Kaplan-Meier method, and the log-rank test was used to compare overall survival.<h4>Results</h4>Three hundred twenty-two patients (median age at diagnosis, 70 years; range, 65-86 years) were included. The median follow-up was 4 years. Sixty-six patients (21%) had a low RDI. Age ≥ 76 years (odds ratio [OR], 2.57; 95% CI, 1.12 to 5.91; <i>P</i> = .03), lower performance status (OR, 4.32; 95% CI, 1.98 to 9.42; <i>P</i> < .001), and use of anthracycline-based or cyclophosphamide, methotrexate, and fluorouracil regimens (OR, 3.47; 95% CI, 1.71 to 7.05; <i>P</i> < .001) were associated with low RDI. The 5-year overall survival probability was 0.80 versus 0.91 in patients with RDI < 85 versus ≥ 85%, respectively (log-rank <i>P</i> = .02).<h4>Conclusion</h4>One in five older patients with EBC treated with standard chemotherapy received low RDI and had inferior survival outcomes. Older patients at risk for low RDI should be identified and targeted upfront before initiating chemotherapy.
Authors
Sedrak, MS; Sun, C-L; Ji, J; Cohen, HJ; Gross, CP; Tew, WP; Klepin, HD; Wildes, TM; Dotan, E; Freedman, RA; O'Connor, T; Chow, S; Fenton, MA; Moy, B; Chapman, AE; Dale, W; Katheria, V; Kuderer, NM; Lyman, GH; Magnuson, A; Muss, HB
MLA Citation
Sedrak, Mina S., et al. “Low-Intensity Adjuvant Chemotherapy for Breast Cancer in Older Women: Results From the Prospective Multicenter HOPE Trial.” Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology, Dec. 2022, p. JCO2201440. Epmc, doi:10.1200/jco.22.01440.
URI
https://scholars.duke.edu/individual/pub1559276
PMID
36455189
Source
epmc
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Published Date
Start Page
JCO2201440
DOI
10.1200/jco.22.01440

The Aging-Cancer Cycle: Mechanisms and Opportunities for Intervention.

Aging is the largest risk factor for the development of cancer. A a growing body of literature indicates that aging and cancer often play a somewhat reciprocal relationship at various times. On the one hand, aging is a "driver" of cancer, and on the other, cancer is a "disease driver" of aging. Here, we synthesize our reflections on the current literature linking cancer and aging, with an eye on fundamental aging processes, such as cellular senescence. Additionally, we consider how interventions that target fundamental aging processes can potentially transform cancer care, from preventing cancer development and progression to reducing the burden of accelerated aging in cancer survivors. Finally, we conclude with a reflection highlighting our vision for future directions to advance the science of cancer and aging and its applicability to improve the care of older adults with cancer.
Authors
Sedrak, MS; Cohen, HJ
MLA Citation
Sedrak, Mina S., and Harvey Jay Cohen. “The Aging-Cancer Cycle: Mechanisms and Opportunities for Intervention.” The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences, Dec. 2022, p. glac247. Epmc, doi:10.1093/gerona/glac247.
URI
https://scholars.duke.edu/individual/pub1560046
PMID
36512079
Source
epmc
Published In
The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
Published Date
Start Page
glac247
DOI
10.1093/gerona/glac247

Association of markers of tumor aggressivity and cognition in women with breast cancer before adjuvant treatment: The Thinking and Living with Cancer Study.

PURPOSE: Tumor features associated with aggressive cancers may affect cognition prior to systemic therapy. We evaluated associations of cognition prior to adjuvant therapy and tumor aggressivity in older breast cancer patients. METHODS: Women diagnosed with non-metastatic breast cancer (n = 705) ages 60-98 were enrolled from August 2010-March 2020. Cognition was measured post-surgery, pre-systemic therapy using self-reported (FACT-Cog Perceived Cognitive Impairment [PCI]) and objective tests of attention, processing speed, and executive function (APE domain) and learning and memory [LM domain]. Linear regression tested associations of pre-treatment tumor features and cognition, adjusting for age, race, and study site. HER2 positivity and higher stage (II/III vs. 0/I) were a priori predictors of cognition; in secondary analyses we explored associations of other tumor features and cognitive impairment (i.e., PCI score < 54 or having 2 tests < 1.5 SD or 1 test < 2 SD from the mean APE or LM domain score). RESULTS: HER2 positivity and the hormone receptor negative/HER2 + molecular subtype were associated with lower adjusted mean self-reported cognition scores and higher impairment rates (p values < .05). Higher stage of disease was associated with lower objective performance in APE. Other tumor features were associated with cognition in unadjusted and adjusted models, including larger tumor size and lower PCI scores (p = 0.02). Tumor features were not related to LM. CONCLUSIONS: Pre-adjuvant therapy cognition was associated with HER2 positivity and higher stage of disease and other features of aggressive tumors. Additional research is needed to confirm these results and assess potential mechanisms and clinical management strategies.
Authors
Root, JC; Zhou, X; Ahn, J; Small, BJ; Zhai, W; Bethea, T; Carroll, JE; Cohen, HJ; Dilawari, A; Extermann, M; Graham, D; Isaacs, C; Jacobsen, PB; Jim, H; McDonald, BC; Nakamura, ZM; Patel, SK; Rentscher, K; Saykin, AJ; Van Dyk, K; Mandelblatt, JS; Ahles, TA
MLA Citation
Root, James C., et al. “Association of markers of tumor aggressivity and cognition in women with breast cancer before adjuvant treatment: The Thinking and Living with Cancer Study.” Breast Cancer Res Treat, vol. 194, no. 2, July 2022, pp. 413–22. Pubmed, doi:10.1007/s10549-022-06623-2.
URI
https://scholars.duke.edu/individual/pub1521722
PMID
35587324
Source
pubmed
Published In
Breast Cancer Res Treat
Volume
194
Published Date
Start Page
413
End Page
422
DOI
10.1007/s10549-022-06623-2

Applying a Life Course Biological Age Framework to Improving the Care of Individuals With Adult Cancers: Review and Research Recommendations.

IMPORTANCE: The practice of oncology will increasingly involve the care of a growing population of individuals with midlife and late-life cancers. Managing cancer in these individuals is complex, based on differences in biological age at diagnosis. Biological age is a measure of accumulated life course damage to biological systems, loss of reserve, and vulnerability to functional deterioration and death. Biological age is important because it affects the ability to manage the rigors of cancer therapy, survivors' function, and cancer progression. However, biological age is not always clinically apparent. This review presents a conceptual framework of life course biological aging, summarizes candidate measures, and describes a research agenda to facilitate clinical translation to oncology practice. OBSERVATIONS: Midlife and late-life cancers are chronic diseases that may arise from cumulative patterns of biological aging occurring over the life course. Before diagnosis, each new patient was on a distinct course of biological aging related to past exposures, life experiences, genetics, and noncancer chronic disease. Cancer and its treatments may also be associated with biological aging. Several measures of biological age, including p16INK4a, epigenetic age, telomere length, and inflammatory and body composition markers, have been used in oncology research. One or more of these measures may be useful in cancer care, either alone or in combination with clinical history and geriatric assessments. However, further research will be needed before biological age assessment can be recommended in routine practice, including determination of situations in which knowledge about biological age would change treatment, ascertaining whether treatment effects on biological aging are short-lived or persistent, and testing interventions to modify biological age, decrease treatment toxic effects, and maintain functional abilities. CONCLUSIONS AND RELEVANCE: Understanding differences in biological aging could ultimately allow clinicians to better personalize treatment and supportive care, develop tailored survivorship care plans, and prescribe preventive or ameliorative therapies and behaviors informed by aging mechanisms.
Authors
Mandelblatt, JS; Ahles, TA; Lippman, ME; Isaacs, C; Adams-Campbell, L; Saykin, AJ; Cohen, HJ; Carroll, J
MLA Citation
Mandelblatt, Jeanne S., et al. “Applying a Life Course Biological Age Framework to Improving the Care of Individuals With Adult Cancers: Review and Research Recommendations.” Jama Oncol, vol. 7, no. 11, Nov. 2021, pp. 1692–99. Pubmed, doi:10.1001/jamaoncol.2021.1160.
URI
https://scholars.duke.edu/individual/pub1493197
PMID
34351358
Source
pubmed
Published In
Jama Oncol
Volume
7
Published Date
Start Page
1692
End Page
1699
DOI
10.1001/jamaoncol.2021.1160
Professor of Medicine

Contact:

Profile

https://scholars.duke.edu/person/harvey.cohen

Email

harvey.cohen@duke.edu
2509 Blue Zone Duke Clinic, Center for Aging, Trent Drive, Durham, NC 27710
Duke Box 3003, Durham, NC 27710