RESUMEN
Epidemiological studies have demonstrated that depression may be a risk factor for Alzheimer's disease (AD); however, the biological mechanisms of the transition from depression to AD are still not clear. Changes of amyloid ß protein (Aß) metabolism and increased glucocorticoid (GC) levels have been found in both depression and AD. Moreover, several studies in animal models have demonstrated that GC administration changes Aß metabolism. To reveal whether GC affects amyloid metabolism in patients with depression, we evaluated serum levels of Aß40, Aß42 and cortisol at admission in 187 inpatients with major depressive disorder (MDD) and 224 healthy comparisons. Additionally, we re-evaluated the serum levels of Aßs in 27 patients with MDD 1 year later. The results of multiple regression analyses revealed that serum cortisol and Aß levels are not correlated at the time of admission. However, serum cortisol levels at admission correlated with serum Aß42 levels and Aß40/Aß42 ratio 1 year later. These findings suggest that increased cortisol in patients with MDD may influence the metabolism of Aß over prolonged periods of time.
Asunto(s)
Enfermedad de Alzheimer/sangre , Péptidos beta-Amiloides/sangre , Trastorno Depresivo Mayor/sangre , Glucocorticoides/sangre , Adulto , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/psicología , Animales , Trastorno Depresivo Mayor/psicología , Femenino , Humanos , Hidrocortisona/sangre , Masculino , Persona de Mediana Edad , Fragmentos de Péptidos/sangre , Análisis de Regresión , Factores de TiempoRESUMEN
OBJECTIVE: Memory impairment in remitted depression is reported to be related to the number of previous depressive episodes. A recent report hypothesized that each depressive episode increases the risk of memory impairment during remission, which further increases the risk of recurrence. We investigated whether the risk for recurrence increased as a function of memory impairment at remission. METHOD: One hundred ten participants with DSM-IV-TR major depressive disorder (MDD) after remission (defined as a score ≤ 7 on the Hamilton Depression Rating Scale) were recruited between April 2004 and March 2012 and were followed up prospectively. All patients were divided into 2 groups: those who had memory impairment and those who had no memory impairment after remission. (Memory impairment was determined with the Wechsler Memory Scale-Revised.) The time to recurrence of depression (a score ≥ 4 on the Clinical Global Impressions-Severity of Illness scale) was compared between the groups prospectively. Kaplan-Meier survival curves, log-rank test for trend for survivor functions, and Cox proportional hazard ratio (HR) estimates for a multivariate model were conducted to examine the risk of recurrence by presence of memory impairment after remission. RESULTS: One hundred nine participants completed this study. In the follow-up period, recurrence occurred in 25 (55.6%) of the 45 patients with memory impairment and 21 (32.8%) of the 64 patients with no memory impairment. In the Kaplan-Meier survival estimates for time to incidence of recurrence in patients with and without memory impairment, the cumulative probability of developing a recurrence for patients with memory impairment was higher than for patients with no memory impairment (log-rank test: χ(2)1 = 4.63, P = .03). Survival analysis was also performed using Cox proportional hazards regression in a multivariate model. The presence of memory impairment remained significantly associated with incidence of recurrence (HR = 2.55; 95% CI, 1.30-4.99; P = .006). CONCLUSIONS: The presence of residual memory impairment in patients with remitted MDD may increase the risk of recurrence.