Evidence for altered hypothalamus-pituitary-adrenal axis functioning in systemic hypertension: blunted cortisol response to awakening and lower negative feedback sensitivity

BACKGROUND: Hypothalamus-pituitary-adrenal (HPA) axis functioning in systemic hypertension is not fully understood. We explored HPA axis activity and feedback sensitivity to oral administration of dexamethasone in systemic hypertension via assessment of the cortisol awakening response (CAR) and the circadian cortisol profile. METHODS: The CAR and circadian cortisol profile were assessed in 20 unmedicated and otherwise healthy middle-aged hypertensive men and in 22 normotensive male controls. Salivary free cortisol measures for the CAR were obtained immediately after awakening and 15, 30, 45, and 60 min thereafter. Circadian cortisol secretion was sampled at 08:00, 11:00, 15:00, and 20:00 h. Assessment of the CAR was repeated on the next day after administration of 0.5mg dexamethasone at 23:00 h on the previous night. RESULTS: Hypertensives had a significantly lower CAR (p<0.02) and significantly reduced suppression of the CAR after dexamethasone administration (p<0.01) than normotensive controls. There were no significant differences in cortisol levels at awakening and in circadian cortisol profiles between hypertensives and normotensives. CONCLUSION: We found evidence for altered HPA axis activity in men with systemic hypertension evident with the CAR. Hypertensives showed relative attenuation in the CAR and in the HPA axis feedback sensitivity following dexamethasone suppression. Such alterations in HPA axis regulation might contribute to the atherosclerotic risk in hypertensive individuals.     

Increased diurnal salivary cortisol in women with borderline personality disorder

Borderline personality disorder (BPD) is characterized by a pervasive pattern of instability in affect regulation, impulse control, interpersonal relationships, and self-image. In previous studies, we have used portable mini-computers to assess the severity of recurrent states of aversive emotional distress and dissociation during ambulatory conditions. Here, we used this approach for the assessment of the hypothalamic–pituitary–adrenal (HPA) axis in patients with BPD. We studied 23 unmedicated female patients with BPD and 24 matched healthy controls. Salivary cortisol was collected from all participants during ambulatory conditions in response to reminders provided by portable mini-computers on 3 consecutive days every 2 h for 14 h after awakening. In addition, cortisol in response to awakening was determined in four 15 min intervals on days 1 and 2. After the last collection of cortisol on the second day, 0.5 mg dexamethasone was administered in order to achieve cortisol suppression on day 3 (low-dose dexamethasone suppression test, DST). Patients with BPD displayed significantly higher salivary cortisol levels than healthy controls as demonstrated by higher total cortisol in response to awakening and higher total daily cortisol levels. There were significantly more non-suppressors of cortisol in the low-dose DST in the patient group when compared to the control group. The ambulatory assessment of saliva cortisol is a suitable approach to study basic parameters of the HPA-axis in patients with BPD. Increased adrenal activity and lowered feedback sensitivity of the HPA-axis may characterise BPD. Further studies have to reveal reasons of heightened adrenal activity in these patients.     

Elevated alpha-amylase but not cortisol in generalized social anxiety disorder

Stress-system dysregulation is thought to increase the risk for anxiety disorders. Here we describe both hypothalamic pituitary adrenal (HPA) axis and autonomic nervous system (ANS) activity in basal non-challenging conditions and after 0.5 mg dexamethasone in generalized social anxiety disorder (gSAD) patients. To ensure stress-free sampling we collected saliva and determined cortisol and alpha-amylase (sAA), the latter a relative new marker of autonomic activity.Forty-three untreated gSAD patients without comorbidity were compared with 43 age and gender matched controls in non-stressed conditions on sAA and cortisol after awakening, during the day (including late evening), and after a low dose (0.5 mg) of dexamethasone. Cortisol and sAA were analyzed with mixed models. Additional analyses were done with paired t-tests. Apart from the assessments in the morning, gSAD patients had significantly higher diurnal and post-dexamethasone 1600 h sAA levels. No differences between gSAD and controls in any cortisol measurements were found.In conclusion, in gSAD in basal, non-stimulated conditions and after dexamethasone, we found hyperactivity of the ANS, as measured with sAA, but not of the HPA-axis. This suggests a relative increased activity of the ANS as compared to the HPA-axis, in line with the observed hyperarousal in gSAD.     

Cortisol awakening response in abstinent alcohol-dependent patients as a marker of HPA-axis dysfunction

Hypothalamo-pituitary-adrenocorticoid (HPA)-axis reactivity to psychosocial or pharmacological stimulants is diminished in alcohol-dependent patients during early abstinence but recovers after several months of abstention. In order to assess the physiological reactivity in the morning we used the cortisol awakening response (CAR) in saliva to compare 24 early abstainers (mean 21.9+/-7.6, range 10-36 days) with 12 alcohol-dependent patients with longer abstention periods (mean 116.8+/-45.7, range 59-230 days) and looked for an association with sleep, especially rapid eye movement (REM) sleep of the preceding night. Both groups did not differ with respect to age, duration of alcohol dependence, daily drinking dosage before detoxification, body mass index, depressivity, level of anxiety, daily cigarette consumption or sleep quality during the preceding 14 days. Sleep in the night before cortisol assessment did not differ with respect to total sleep time (412.4+/-35.9 vs. 407.0+/-38.7 min). Immediately upon awakening and 15, 30, 45 and 60 min later, specimens of salivary cortisol were collected. While starting from equal levels upon awakening longer abstaining patients with alcohol dependence showed a stronger CAR (ANOVA with repeated measurement, time x group effect: F=4.33, p<0.01) with distinctly higher cortisol levels 45 and 60 min after awakening (T=3.79, p<0.001 and T=3.06, p<0.005, respectively). Across both groups the time spent in REM-sleep only correlated with cortisol levels upon awakening (r=0.33, p<0.05). Our data indicate that CAR is a useful tool for investigating alterations in the HPA-axis regulation in abstaining alcohol-dependent patients.     

No effects of repeated forced wakings during three consecutive nights on morning cortisol awakening responses (CAR): a preliminary study

OBJECTIVE: The cortisol awakening response (CAR) is considered a reliable measure for the acute reagibility of the hypothalamus-pituitary-adrenal (HPA) axis. Whether repeated nightly awakenings at different times during the night also stimulate the HPA-axis and whether, consequently, the CAR is altered has not been tested, so far. We aimed to investigate whether three experimentally induced awakenings during three consecutive nights would be associated with HPA-axis stimulation and an altered morning CAR. METHODS: The study sample consisted of 13 healthy adult women who were waken up three times in each of three consecutive nights. Cortisol levels were measured immediately and 15 min after each awakening in the night and in the morning, respectively. Also, the morning CARs after three nights of undisturbed sleep were assessed. RESULTS: A significant difference between night time cortisol responses to awakening and the morning CAR was found. While cortisol levels during the first half of the night did not rise significantly after awakening in the night, some reactivity was seen during awakenings in the very early morning hours, and pronounced awakening responses were observed in the morning before getting out of bed. Interestingly, the morning CAR after disturbed sleep did not differ from the morning CAR following undisturbed sleep. CONCLUSION: In healthy female individuals, the morning CAR appears to be unchanged even if sleep was repeatedly interrupted by forced wakings.     

The morning salivary cortisol response in burnout

OBJECTIVES: The aim of the present study was to examine the free salivary cortisol response to awakening in men and women reporting low, moderate, and high levels of burnout. METHODS: Twenty-two patients on sick leave due to burnout were compared with 22 working participants with low and 20 working participants with intermediate scores on the Shirom-Melamed Burnout Questionnaire (SMBQ), with regard to the free salivary cortisol response to awakening. Saliva samples were collected upon awakening and at +15, +30, and +60 min thereafter. RESULTS: Female burnout patients had higher cortisol levels than did the females with low burnout at awakening and at +15, +30, and +60 min after awakening. They also had a greater area under the curve (AUC) for salivary cortisol than did the female participants with low burnout. Male participants with moderate levels of burnout had higher cortisol levels at +60 min after awakening compared with males with low burnout. CONCLUSIONS: The results of the present study indicate a dysregulation in hypothalamic-pituitary-adrenocortical axis (HPA axis) activity, characterised by elevated morning salivary cortisol levels, among female burnout patients. Among males, increased cortisol levels were observed among participants with moderate levels of burnout, but not among patients or healthy controls.     

Enhanced cortisol suppression in response to dexamethasone administration in traumatized veterans with and without posttraumatic stress disorder

BACKGROUND: While enhanced cortisol suppression in response to dexamethasone is one of the most consistent biological findings in posttraumatic stress disorder (PTSD), the relative contribution of trauma exposure to this finding remains unclear. METHODS: Assessment of diurnal salivary cortisol levels and 1600 h salivary cortisol before and after oral administration of 0.5mg dexamethasone in veterans with PTSD, veterans without PTSD (trauma controls) and healthy controls. Assessment of 1600 h plasma cortisol, ACTH and corticotrophin binding globulin (CBG) in response to dexamethasone in PTSD patients and trauma controls. RESULTS: Both PTSD patients and trauma controls demonstrated significantly more salivary cortisol suppression compared to healthy controls. Salivary cortisol, plasma cortisol and ACTH suppression as well as CBG levels did not differ between PTSD patients and trauma controls. PTSD patients showed a reduced awakening cortisol response (ACR) compared to healthy controls that correlated significantly with PTSD symptoms. No significant differences were observed in ACR between PTSD patients and trauma controls. CONCLUSIONS: These data suggest that enhanced cortisol suppression to dexamethasone is related to trauma exposure and not specifically to PTSD. The correlation between the ACR and PTSD severity suggests that a flattened ACR may be a result of clinical symptoms.     

Hypothalamic-pituitary-adrenal axis dysregulation among diabetic outpatients

We compared insulin-requiring diabetic outpatients (n = 49) with normal controls (n = 42) for indices of hypothalamic-pituitary-adrenal (HPA) axis activity. Diabetic patients showed significantly elevated 9 a.m. plasma levels of cortisol as well as significantly elevated plasma levels of cortisol and adrenocorticotropic hormone (ACTH) at both 4 p.m. before and 4 p.m. after dexamethasone. Also, there was a significant correlation between postdexamethasone plasma levels of ACTH and duration of diabetes. These results suggest that HPA-axis dysregulation is found among diabetic outpatients. The possible psychiatric implications are discussed.     

Salivary cortisol day profiles in elderly with mild cognitive impairment

It is unknown whether hypothalamus-pituitary-adrenal (HPA) axis dysfunction is associated with the memory impairments observed among elderly participants with mild cognitive impairment (MCI), a group considered at increased risk for Alzheimer's disease (AD). Therefore, salivary cortisol levels were measured at six points over the course of the day while at-home in MCI participants (n=16), normal elderly (n=28), and young controls (n=14). Results revealed that MCI participants did not show elevated salivary cortisol levels. The 9 a.m. cortisol level of the MCI group was significantly lower than the 9 a.m. level of the young controls, but did not differ from those of the normal elderly group. In contrast to the other two groups, within the MCI group mean cortisol levels were inversely related to immediate recall of paragraphs. No association was observed between mean cortisol levels and performance in paired associates and digit span. Whether cortisol levels, in conjunction with other factors, such as hippocampal volume, will lead to improved prediction of future decline to AD in participants with MCI remains to be established in longitudinal studies.     

High cortisol awakening response is associated with an impairment of the effect of bright light therapy

Objective: We investigated the predictive validity of the cortisol awakening response (CAR) in patients with non‐seasonal major depression. Method: Patients were treated with sertraline in combination with bright or dim light therapy for a 5‐week period. Saliva cortisol levels were measured in 63 patients, as an awakening profile, before medication and light therapy started. The CAR was calculated by using three time‐points: awakening and 20 and 60 min after awakening. Results: Patients with low CAR had a very substantial effect of bright light therapy compared with dim light therapy, whereas patients with a high CAR had no effect of bright light therapy compared with dim light therapy. Conclusion: High CAR was associated with an impairment of the effect of bright light therapy. This result raises the question of whether bright light acts through a mechanism different from that of antidepressants.     

A longitudinal study on cortisol and complaint reduction in burnout

Several studies have investigated the association between burnout and HPA-axis functioning, but the results are far from consistent. This does not preclude the possibility that within a group of burnout patients a recovery of symptoms in a longitudinal course corresponds to (changes in) cortisol parameters. The latter possibility is tested in the present study before and after treatment, and at follow-up. HPA-axis functioning and burnout complaints were assessed in burned-out participants at baseline (n=74), post-treatment (n=62) and at follow-up (n=53). Multilevel regression analysis was used to test the hypothesis. Burnout complaints were significantly reduced at 8.5 months post-treatment, but there was no further reduction in complaints at follow-up 6.3 months later. Cortisol after awakening, and after dexamethasone intake showed no changes from baseline to post-treatment and follow-up. There was a small decline in cortisol during the day over the longitudinal course. The cortisol level after awakening in the longitudinal course showed significant positive association with the initial exhaustion level, a negative association with the change in the burnout exhaustion score, and a positive association with the change in depression. Although these associations are statistically significant, they only explain a small fraction of the variance in cortisol after awakening between and within persons. This implies that changes at symptom level are hardly related to changes in cortisol functioning, therefore the clinical implications of this finding are limited.     

Platelet tritiated imipramine binding and serotonin uptake in depressed patients and controls. Relationship to plasma cortisol levels before and after dexamethasone administration

We measured platelet tritiated imipramine binding and serotonin uptake in 51 depressed patients and 43 normal controls. Although there were no significant differences in platelet 3H-imipramine binding or serotonin uptake when the total group of depressed patients was compared with controls, depressed women (n = 32) had a significantly lower maximal density of 3H-imipramine binding sites (beta max) than control women (n = 25). Moreover, among the total group of depressed patients, there were significant negative correlations between the beta max values and plasma cortisol levels at 4 PM (n = 41) and 11 PM (n = 41) following dexamethasone administration. These negative correlations between beta max and cortisol levels were strongest among melancholic patients both at 4 PM before dexamethasone administration (n = 14) and at 11 PM after dexamethasone administration (n = 15). These data suggest that the reported decrease in beta max found among depressed patients may be related to and is perhaps secondary to the hypercortisolemia of depression.     

HPA-axis activity and externalizing behavior problems in early adolescents from the general population: the role of comorbidity and gender The TRAILS study

Contradictory findings on the relationship between hypothalamus-pituitary-adrenal (HPA)-axis activity and externalizing behavior problems could be due to studies not accounting for issues of comorbidity and gender. In a population-based cohort of 1768 (10- to 12-year-old) early adolescents, we used a person-oriented approach and a variable-oriented approach to investigate whether comorbidity with internalizing behavior problems and gender moderate the relationship between HPA-axis activity (cortisol awakening response and evening cortisol levels) and externalizing behavior problems. We found that: (1) in early adolescents with pure externalizing behavior problems, there was a particularly strong effect of gender, in that girls showed significantly higher total cortisol levels after awakening (AUC(G) levels) and a significantly higher cortisol awakening response (AUC(I) levels) than boys. (2) Girls with pure externalizing behavior problems showed a significantly higher cortisol awakening response (AUC(I) levels) than girls without behavior problems or girls with comorbid internalizing behavior problems. This effect was absent in boys. (3) Externalizing behavior problems, in contrast to internalizing behavior problems, were associated with higher evening cortisol levels. This effect might, however, result from girls with externalizing behavior problems showing the highest evening cortisol levels. Overall, we were unable to find the expected relationships between comorbidity and HPA-axis activity, and found girls with pure externalizing behavior problems to form a distinct group with regard to their HPA-axis activity. There is need for prospective longitudinal studies of externalizing behavior problems in boys and girls in relation to their HPA-axis activity. It would be useful to consider how other risk factors such as life events and family and parenting factors as well as genetic risks affect the complex relationship between externalizing behavior problems and HPA-axis activity.     

PTSD symptoms predict waking salivary cortisol levels in police officers

This study examines whether pre- or post-dexamethasone salivary cortisol is related to cumulative critical incident exposure, peritraumatic responses, or post-traumatic stress disorder (PTSD) symptom severity. Thirty active duty police officers completed the study protocol, which included measures of peritraumatic emotional distress, peritraumatic dissociation, duty-related trauma exposure, and PTSD symptoms. Salivary cortisol was consolidated into three outcome variables: (1) pre-dexamethasone free cortisol levels at 1, 30, 45, and 60 min after awakening, (2) post-dexamethasone cortisol levels at the identical wake times, and (3) percentage of cortisol suppression. Control variables included age, gender, average daily alcohol use, night shift work, routine work environment stressors, and salivary dexamethasone levels. Zero order correlations showed that greater levels of PTSD symptoms, peritraumatic distress, and peritraumatic dissociation were associated with lower levels of pre-dexamethasone cortisol levels on awakening, but were not associated with the other two cortisol variables. A trend was also noted for older subjects to have lower pre-dexamethasone cortisol on awakening. When these four predictors were entered simultaneously in a regression analysis, only age and PTSD symptom severity significantly predicted pre-dexamethasone awakening cortisol levels. These results replicate previous research indicating a relationship between greater PTSD symptoms and lower levels of basal cortisol on awakening, and extend this finding to a previously unstudied non-treatment seeking population, urban police.     

The cortisol awakening response in amyotrophic lateral sclerosis is blunted and correlates with clinical status and depressive mood

Considerable evidence indicates that amyotrophic lateral sclerosis (ALS), a progressive neurodegenerative disease of the motor system, has an enormous impact on the patient's emotional and physical well-being. As previous findings indicated that particularly the rise in cortisol levels immediately after awakening, i.e., the cortisol awakening response (CAR), is associated with indices of physical and emotional well-being, we compared the CAR of 29 admitted ALS patients with that of 12 age-matched caregiver controls. Saliva samples for cortisol measurement were collected immediately, 15, 30 and 45 min after awakening. The severity of ALS progression was quantified using the ALS functional rating scale (ALSFRS) and manual muscle test (MMT). Depressive mood status in ALS patients was determined with the Beck Depression Inventory (BDI) and Hamilton Depression Rating Scale (HDRS). Salivary cortisol levels of ALS patients did not differ from those of caregiver controls at awakening, 15 min or 45 min after awakening, but were significantly lower at 30 min after awakening. Area under the curve analysis confirmed that the CAR was significantly smaller in ALS patients than in caregiver controls. A smaller CAR in ALS patients was significantly correlated to poorer clinical status, as assessed with both the ALSFRS and MMT rating instruments. Further, a smaller CAR significantly correlated with a more severe depressive mood status. No correlations were observed between total cortisol output during the first 45 min post-awakening and clinical or depressive status. In conclusion, our findings indicate that ALS patients show a blunted CAR, correlated with disease and depression severity.     

Sleep disturbances are correlated with decreased morning awakening salivary cortisol

Morning and evening salivary cortisol levels were correlated with sleep parameters in 14 patients with primary insomnia and 15 healthy controls. Salivary cortisol was sampled immediately after awakening (T1), 15 min later (T2), and immediately before going to bed (T3) for 1 week at home. In parallel with this, subjects estimated parameters of sleep in a daily sleep log. Patients and controls were all non-smokers who did not differ regarding morning awakening time or bedtime. Cortisol after awakening was significantly decreased in primary insomnia. Salivary cortisol at the time of awakening correlated negatively with the subjective estimation of sleep quality, i.e. a low salivary cortisol level directly after awakening correlated with a higher frequency of nightly awakenings (r = -0.50), a diminished sleep quality (r = -0.34) and a decreased feeling of recovery after awakening (r = -0.35; all p < 0.05). Furthermore, awakening cortisol was negatively correlated with the Pittsburgh Sleep Quality Index (r = -0.43) and with a questionnaire on sleep-related cognitions with the subscales rumination in bed (r = -0.56 ) and focusing on sleep-related thoughts (r = -0.46; all p < 0.05).     

Higher cortisol awakening response in young adolescents with persistent anxiety problems

OBJECTIVE: The aims of the present study were to test the association between current anxiety problems and basal cortisol levels in a large population sample of young preadolescents, and to test if HPA-axis activity differs between individuals with no, only current, or persistent anxiety problems. METHOD: Cortisol levels of 10- to 12-year olds (n = 1,768) from the general population were measured on three time points during the day. A self-report questionnaire (RCADS) was used to assess current anxiety, a parent-report questionnaire (TPBQ) to assess anxiety problems at age 4. RESULTS: Associations between cortisol levels and current anxiety problems were not found. However, individuals with persistent anxiety problems had higher morning cortisol levels and a higher cortisol awakening response. CONCLUSION: Apparently, only persistent, and not current, anxiety problems are associated with higher HPA-axis activity. Alterations in HPA-axis activity might underlie persistent anxiety problems, or result from the stress accompanied by persistent anxiety problems.     

Clinical burnout is not reflected in the cortisol awakening response, the day-curve or the response to a low-dose dexamethasone suppression test

Burnout is presumed to be the result of chronic stress, and chronic stress is known to affect the HPA-axis. To date, studies on HPA-axis functioning in burnout have showed inconsistent results. In the present study, a large sample (n=74) of clinically diagnosed burnout individuals, mostly on sick-leave, were included and compared with 35 healthy controls. Salivary cortisol was sampled on 2 days to determine the cortisol awakening response (CAR) and the day-curve. In addition, the dexamethasone suppression test (DST) was applied to assess the feedback efficacy of the HPA-axis. There were no differences observed in the CAR, day-curve or CAR after DST in the burnout group as compared to a healthy control group. Burnout shows overlap in symptoms with chronic fatigue syndrome (CFS) and depression. Therefore, differential changes in HPA-axis functioning that resemble the hypo-functioning of the HPA-axis in CFS, or rather the hyper-functioning of the HPA-axis in depression, might have obscured the findings. However, no effect of fatigue or depressive mood on HPA-axis functioning was found in the burnout group. We concluded that HPA-axis functioning in clinically diagnosed burnout participants as tested in the present study, seems to be normal.     

Endocrine stress responses in TH1-mediated chronic inflammatory skin disease (psoriasis vulgaris)--do they parallel stress-induced endocrine changes in TH2-mediated inflammatory dermatoses (atopic dermatitis)?

In previous research we reported attenuated responsiveness of the hypothalamus-pituitary-adrenal (HPA) axis and further, an increased reactivity of the sympathetic adrenomedullary (SAM) system to stress in patients suffering from atopic dermatitis (AD). AD is a chronic inflammatory skin disease mainly triggered by TH(2)-dependent inflammatory processes. The specific goal of the present study was to investigate whether altered HPA axis and SAM system responsiveness to stress can also be found in TH(1)-mediated inflammatory conditions. Patients with psoriasis (PSO; n=23), a TH(1)-mediated inflammatory (autoimmune) skin disease and healthy controls (n=25) were exposed to a standardized laboratory stressor (TSST) which mainly consists of a free speech and a mental arithmetic task in front of an audience. To investigate HPA axis and SAM system responsiveness, cortisol, ACTH, and catecholamines were determined before and after the stress test. In addition, cortisol levels after awakening and cortisol levels during the day (short diurnal profile) were determined. In order to test feedback sensitivity of the HPA axis, a dexamethasone (DEX) suppression test (0.5 mg) was performed. Analysis of cortisol and ACTH levels after the stress test yielded no significant differences between PSO subjects and controls indicating no altered HPA axis function in this patient group. Further, no between-group differences were found in cortisol levels after awakening or during the day (short diurnal profile). Additionally, no difference between PSO and healthy subjects in the feedback sensitivity of the system could be found (DEX test). However, PSO patients showed elevated epinephrine (F(3,102)=4.7; p<0.005) and norepinephrine (F(3,135)=2.7; p<0.05) levels in response to the stress test when compared to the controls. These findings suggest no altered HPA axis responsiveness, but increased reactivity of the SAM system in TH(1)-mediated chronic inflammatory skin disease.     

Decreased Levels of Circulating Adiponectin in Mild Cognitive Impairment and Alzheimer’s Disease

Adiponectin, an adipocytokine released by the adipose tissue and has important roles in the metabolic regulation and inflammatory control, may play an important roles in the physiopathology of psychiatric and neurodegenerative disorders. The aim of the present work was to evaluate adiponectin serum levels in patients with mild cognitive impairment (MCI) and Alzheimer’s disease (AD) as compared to cognitively healthy elders and to correlate these levels with clinical and cognitive parameters. We further evaluated whether circulating adiponectin levels could predict progression from MCI to Alzheimer’s disease upon follow-up. We recruited 157 subjects (41 with AD, 65 with MCI and 51 elderly controls) in the baseline assessment. Follow-up data were available for 54 subjects with MCI and 43 controls in whom we ascertained the conversion to AD and the progression of cognitive impairment. Adiponectin was assayed by sandwich ELISA. Serum levels of adiponectin were significantly lower in MCI and AD as compared to controls (p < 0.001). After controlling for age, educational level and APOE genotype, adiponectin levels remained significantly reduced in these groups (p < 0.001). Circulating adiponectin levels did not predict cognitive decline in the elderly controls (i.e., progression from normal cognition to MCI) or progression to Alzheimer’s disease in subjects with MCI. We conclude that lower levels of adiponectin were associated with cognitive dysfunction, though it did not predict additional cognitive decline and conversion to dementia in this cohort of elderly subjects. Decreased adiponectin may be a surrogate marker of the pathological process in AD, linking clinical comorbidities, inflammation and cognitive dysfunction.