RESPONSE LETTER TO DR. FINUCANE To the Editor: We thank Dr. Finucane for his letter, which addresses the clinical implications our study, ‘‘Anemia and 9-Year Domain-Specific Cognitive Decline in Community- Dwelling Older Women: The Women’s Health and Aging Study II.’’ In our observational study, we documented a longitudinal association between mild anemia and faster rates of cognitive decline in community-dwelling older women. We then speculated as to the nature of the observed associations (whether anemia is a causal risk factor vs a marker of residual or unmeasured confounding factor(s)). Such a distinction is critical for decision-making; if an as- sociation is causal, it might be theoretically possible to de- crease risk of adverse functional outcomes through risk factor correction; randomized clinical trial (RCT) data would determine whether correction of a causal risk factor indeed offers protection. 1 It is within this context that we stated, ‘‘If this relationship is causal, it is possible that treatment of anemia could prevent or postpone cognitive decline.’’ 2 We did not conclude that the association was causal and reinforce here that our findings should not be interpreted as the basis for anemia-related treatment rec- ommendations for cognitive decline prevention. The mechanistic hypotheses discussed in our article about the link between anemia and cognition are not new in the literature. 3,4 Unfortunately, data are lacking on the physiological relationship between hemoglobin concentra- tion and cerebral oxygenation to support or refute this hypothesis. We agree that suggesting treatment of anemia for cog- nitive decline prevention for older adults at this time is prob- lematic, given that existing RCT data do not support such a suggestion. Such data will be necessary to determine how anemia correction customized to the different etiologies un- derlying anemia might affect cognitive function. Erythro- poiesis-stimulating agents (ESAs) are currently recommended only in specific clinical contexts, and guidelines have been recently revised on the basis of growing safety concerns. We are not proposing any departure from current clinical guide- lines. Discussion is on-going about the investigation of ESAs for functional decline prevention in the context of less-well- studied anemia types (e.g., unexplained anemia). Currently, there are no safe and effective pharmaco- logical agents shown to prevent or delay progressive cog- nitive decline and impairment in community-dwelling older adults. The concerns that our colleagues addresses highlight some of the challenges associated with identifying safe and modifiable risk factors as targets for prevention of cognitive impairment and dementia. Given the growing prevalence of mild cognitive impairment and dementia, this research and discussion is particularly urgent. Paulo H.M. Chaves, MD, PhD Department of Epidemiology Center on Aging and Health Department of Medicine Division of Geriatric Medicine and Gerontology Jennifer A. Deal, MHS Department of Epidemiology Center on Aging and Health Michelle C. Carlson, PhD Center on Aging and Health Department of Mental Health The Johns Hopkins Medical Institutions Baltimore, Maryland ACKNOWLEDGMENTS Conflict of Interest: Dr. Chaves has been the recipient of a research grant from Amgen, Inc. and has served as a con- sultant for FibroGen, Inc. None of the products developed or marketed by these companies are discussed in this letter. Research supported by National Institutes of Health (NIH), National Institute on Aging (NIA) Grants R01 AG19825-02, R01 AG11703-10, T32 AG00247, and R37 AG19905; by NIA, Claude D. Pepper Older Americans In- dependence Centers Grant P30 AG021334; and by NIH, National Center for Research Resources OPD-GCRC Grant RR00722. Author Contributions: All contributed equally to the concept, design, acquisition of subjects, analysis and inter- pretation of data, and manuscript preparation. Sponsor’s Role: None. REFERENCES 1. Chaves PH. Functional outcomes of anemia in older adults. Semin Hematol 2008;45:255–260. 2. Deal JA, Carlson MC, Xue QL et al. Anemia and 9-year domain-specific cog- nitive decline in community-dwelling older women: The Women’s Health and Aging Study II. J Am Geriatr Soc 2009;57:1604–1611. 3. Atti AR, Palmer K, Volpato S et al. Anaemia increases the risk of dementia in cognitively intact elderly. Neurobiol Aging 2006;27:278–284. 4. Shah RC, Wilson RS, Tang Y et al. Relation of hemoglobin to level of cognitive function in older persons. Neuroepidemiology 2009;32:40–46. THE OVERLAP SYNDROME OF DEPRESSION AND DELIRIUM IN ELDERLY PATIENTS: A COMMENT To the Editor: In their article recently published in the Journal of the American Geriatrics Society , 1 Givens and colleagues investigate whether overlap syndrome of coex- isting depression and incident delirium is associated with adverse outcomes, including functional decline, nursing home placement, and death at 1 and 12 months in a pop- ulation of older adults hospitalized in a medicine service. We would like to contribute to this topic with our per- sonal data, referring to a population of patients from an inpatient rehabilitation facility. From January 2002 to De- cember 2005, all patients consecutively admitted to our Rehabilitation and Aged Care Unit (RACU) for the first time were evaluated using a standardized multidimensional assessment including age, sex, living arrangement, somatic and nutritional health (Charlson Comorbidity Index, 2 al- bumin and C-reactive protein serum levels, number of drugs at discharge), cognitive status (Mini-Mental State Examin- ation, MMSE), and functional status (Barthel Index based on proxy reports and referenced to 1 month before admis- sion for nonsurgical patients and before the acute event that led to surgery). The presence of delirium was investigated daily using the Confusion Assessment Method 3 and defined as the presence of acute onset or fluctuating course, inat- tention, and disorganized thinking or altered level of consciousness. Depressive symptoms were assessed using LETTERS TO THE EDITOR 995 JAGS MAY 2010–VOL. 58, NO. 5