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Alterations in the hypothalamic-pituitary-adrenal axis have been noted in people with Alzheimer disease (AD) and in the people caring for them. In a case-control study, we assessed whether the cortisol response at awakening and diurnal cortisol would reflect these changes. AD patients, their caregivers, and healthy senior noncaregivers collected saliva within 5 minutes of waking, 30 minutes after waking, before lunch, 1 hour after lunch, and at 11 pm or when getting ready for bed. They also completed a Perceived Stress Scale. Total cortisol for the day after adjusting for antidepressant use revealed a group effect [F(2,39)=12.49, P<0.0001], with mild AD patients and caregivers having higher cortisol values. Unlike the noncaregivers (t=−1.15, df=14, P>0.27), both cortisol values of the AD caregivers (t=−2.96, df=16, P<0.03) and the AD patients' (t=−2.5, df=14, P<0.01) increased between awakening and 30 minutes afterward. There were also group differences at awakening [F(2,48)=4.6, P=0.012] adjusting for antidepressant use and 30 minutes after waking adjusting for antidepressant use and awakening cortisol [F(2,46)=4.7, P=0.014<0.02). AD patients (r=0.45, P=0.08) and caregivers (r=0.44, P=0.10) with higher cortisol values 30 minutes after waking also showed a trend toward higher perceived stress scores. Salivary cortisol and cortisol response on awakening may enhance future studies relating free cortisol to subjective psychologic and physiologic markers.