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Recent Publications

Functional Recovery after Surgery:

Pisani MA,1 Albuquerque A,1 Marcantonio ER, Jones RN, Gou RY, Fong TG, Schmitt EM, Tommet D, Isaza Aizpurua II, Alsop DC, Inouye SK,2 Travison TG.2 Hospital readmission is associated with both acute and sustained delays in functional recovery during the 18 months following elective surgery: The SAGES Study. J Am Geriatr Soc. 2016. In Press. PMC in process. (1these authors contributed equally as co-first authors; 2these authors contributed equally as co-senior authors).  

Because hospitalization as a result of any admitting diagnosis has been short to contribute to a subsequent decline is health, we sought to determine the effects of rehospitalization on functional recovery after elective surgery. To gauge rehospitalization, we conducted interviews with a prospective cohort of elderly elective surgery patients  and their families over an 18 month period; to determine physical function, we employed the Instrumental Activities of Daily Living, Activities of Daily Living, the SF-12 Physical Component Summary, and a standardized functional composite. Our results indicate that readmissions may contribute to a delay in functional recovery, impacting all facets of physical function. These findings accord with a growing consensus that interventions aimed at preventing unanticipated readmissions or reducing the functional effects of readmission are of great benefit to older adults undergoing surgery.

Hshieh TT,1 Saczynski J,1 Gou RY, Marcantonio E, Jones RN, Schmitt E, Cooper Z, Ayres D, Wright J, Travison TG,2 Inouye SK.2 Trajectory of functional recovery after postoperative delirium in elective surgery. Ann Surg. 2016. Epub ahead of print. PMC in process. (1these authors contributed equally as co-first authors; 2these authors contributed equally as co-senior authors).  

In order to describe functional recovery after elective surgery and determine whether postoperative recovery trajectory differs between those who do and do not develop delirium, we employed a prospective observational study involving the SAGES cohort. Delirium incidence and severity were assessed during the hospital stay of elderly individuals undergoing major elective surgery; functional recovery was gauged by administration of the Activities of Daily Living and Instrumental Activities of Daily Living Scales and Phsycial Component Summary of the Short-Form 12 before surgery and at 1, 2, 6, 12, and 18 month postoperative intervals. Our findings indicate that delirium is significantly correlated with impairment to functional recovery, up to 18 months postoperative. Moreover, individuals at high risk for delirium may reap more functional benefit from elective surgery through  multifacted preoperative interventions and an individualized postoperative course of care.

Neuroimaging and Delirium

Hshieh TT, Dai W, Cavallari M, Guttmann CRG, Meier DS, Schmitt EM, Dickerson BC, Press DZ, Marcantonio ER, Jones RN, Gou YR, Travison TG, Fong TG, Ngo L, Inouye SK,* Alsop DC*. Cerebral blood flow MRI in the nondemented elderly is not predictive of post-operative delirium but is correlated with cognitive performance. J Cereb Blood Flow Metab. 2016. Epub ahead of print. PMC in process. (*these authors contributed equally as co-senior authors).

Abnormalities in cerebral blood flow (CBF) can indicate cerebrovascular dysfunction as global and regional CBR abberances have arisen during brain imaging of patients experiencing delirium. We probed the possible correlation between Arterial Spin Labeling (ASL) MRI measures of preoperative CBF with postoperative delirium incidence and severity, along with the cross-sectional association of CBF with patients' baseline performance on neuropsychological tests and their composite general cognitive performance (GCP). Our results indicate that ASL is a feasible instrument for examining association between CBF and age-related cognitive performance. Moreover, ASL CBF measures in regions associated with preclinical Alzheimer's Disease correlated with cognition but did not indicate a pathophysiological risk for delirium.

Cavallari M,1 Hshieh TT,1 Guttmann CG, Ngo LH, Meier DS, Schmitt EM, Marcantonio ER, Jones RN, Kosar CM, Fong TG, Press DZ, Inouye SK,2 Alsop DC,2 SAGES Study Group. Brain atrophy and white matter hyperintensities are not significantly associated with incidence and severity of postoperative delirium in older persons without dementia. Neurobiol Aging. 2015; 36:2122-2129. PMC4433616 (1these authors contributed equally as co-first authors; 2these authors contributed equally as co-senior authors). 

This study used state-of-the-art magnetic resonance imaging (MRI) to examine a cohort of patients without dementia undergoing elective surgery. There were no significant differences in brain volume, hippocampal volume, or white matter damage between patients with and without delirium. Future studies may consider whether other measures of brain pathology may be useful for predicting delirium.

Cognitive Performance and Delirium:

Fong TG,* Hshieh TT,* Wong B, Tommet D, Jones RN, Schmitt EM, Puelle MR, Saczynski J, Marcantonio ER, Inouye SK. Neuropsychological profiles of an elderly cohort undergoing elective surgery and the relationship of cognitive performance with delirium. J Am Geriatr Soc. 2015; 63:977-82. PMC4497521 (*these authors contributed equally). 

We examined neuropsychological test performance in older adults in the SAGES study. We wanted to test if patients who developed delirium after surgery performed differently on neuropsychological tests prior to the surgery compared to patients who did not develop post-operative delirium. We found that patients who developed delirium had lower scores on tests in areas of complex attention, executive function, and verbal knowledge before surgery. Future studies will need to examine how cognitive performance may predispose individuals to developing delirium, and could help pave the way to greater understanding of the mechanisms of delirium. Future work may also consider how interventions such as training programs that boost “brain fitness” might strengthen attention and memory, preventing the post-operative cognitive decline that is frequently observed in older adults.

Cognitive Reserve and Delirium risk

Saczynski JS,* Inouye SK,* Kosar C, Tommet D, Marcantonio ER, Fong T, Hshieh T, Vasunilashorn S, Metzger ED, Schmitt E, Alsop DC, Jones RN. Cognitive and brain reserve and the risk of postoperative delirium in older patients. Lancet Psychiatry. 2014; 1:437-443. PMC4307596 (*these authors contributed equally).

This is the first study to simultaneously examine multiple markers of cognitive and brain reserve as risk factors for the incidence of postoperative delirium. The results indicate that of eight markers of cognitive and brain reserve, only performance on a verbal intelligence test, the Wechsler Test of Adult Reading, was associated with the development of delirium. Our findings suggest that the reserve markers that are important for delirium may be different from those considered to be important for dementia. One important area for future research is to examine whether cognitive and brain reserve markers are associated with functional and cognitive recovery following delirium.

Pain and Depression:

*Kosar CM, *Tabloski PA, Travison TG, Jones RN, Schmitt EM, Puelle MR, Inloes JB, Saczynski JS, Marcantonio ER, Meagher D, *Reid MC, *Inouye SK. Effect of Preoperative Pain and Depressive Symptoms on the Development of Postoperative Delirium. Lancet Psychiatry. 2014; 1:431-436. PMC4307613 (*these authors contributed equally).

Older adults who experience pain and depressive symptoms prior to surgery are more likely to have delirium following surgery. Patients with depressive symptoms had a 21% increased risk of delirium. Physicians considering surgery for older patients should therefore be aware of the delirium risk and potential contributions of pain and depressive symptoms in their preoperative evaluations.

Genetic risk marker:

Vasunilashorn S, Ngo L, Kosar CM, Fong TG, Jones RN, Inouye SK,* Marcantonio ER.* Does Apolipoprotein E Genotype Increase Risk of Postoperative Delirium? Am J Geriatr Psychiatry. 2015; 23:1029-37. PMC4591079 (*these authors contributed equally as co-senior authors).

Apolipoprotein ε4 (ApoE) is a known risk factor for Alzheimer’s Disease, and we predicted that the gene might also be a risk factor for delirium. However, our results show that ApoE does not affect risk for delirium, which suggest that delirium is not a sign of early Alzheimer’s but its own clinical condition.



The CAM-S: A New Scoring System for Delirium Severity

Inouye SK, Kosar CM, Tommet D, Schmitt EM, Puelle MR, Saczynski JS, Marcantonio ER, Jones RN. The CAM-S: Development and Validation of a New Scoring System for Delirium Severity in 2 Cohorts. Ann Intern Med. 2014; 160: 526-533. PMC4038434.

Dr. Inouye and colleagues developed the CAM-S, a delirium severity scoring system that has shown strong correlation with clinical outcomes in hospitalized older patients, including length of stay, functional decline, and death. The new scoring system, CAM-S, is based on the Confusion Assessment Method (CAM) and standardizes the measurement of delirium severity for both clinical and research uses. This measure holds great promise to improve understanding of the effects of delirium on clinical care, prognosis, pathophysiology, and response to treatment.