Faculty Bibliography

Depression has been linked to Alzheimer's disease as either an increased risk factor for its development or as a prodromal symptom. The neurobiological basis for such an association, however, remains poorly understood. Numerous studies have examined whether changes in amyloid beta (Abeta) metabolism, which are implicated in the pathogenesis of Alzheimer's disease, are also found in depression. In this paper, we investigated the relationship between depressive symptoms and cerebrospinal fluid (CSF) Abeta indices in otherwise healthy, cognitively normal elderly with late-life major depression (LLMD) and controls using a longitudinal approach, which is a novel contribution toward the literature. Significantly lower levels of CSF Abeta42 were observed in the LLMD group at baseline and were associated with more severe depressive symptoms. During longitudinal follow-up, the depressed group remained cognitively unchanged, but was significantly less depressed than at baseline. A greater improvement in depressive symptoms was associated with increases in CSF Abeta42 levels in both groups. Increases in CSF Abeta42 and Abeta40 were also associated with increased CSF total-tau levels. Our results suggest that LLMD may be associated with state-dependent effects of CSF Abeta42 levels. Future studies should determine whether the association reflects state-dependent changes in neuronal activity and/or brain amyloid burden in depression.

Background: Numerous studies have suggested that the APOE e4 allele, an established risk factor for AD, may act synergistically with depression to increase the risk for progressive cognitive decline and conversion to MCI/AD. However, these findings remain controversial and have been reported inconsistently. A possible reason for these conflicting results is differences in methodologies across studies, including differences in the definition of depression, failure to properly diagnose depression or AD, short duration of follow up, differences in age, and possible inclusion of individuals with preexisting cognitive decline or MCI. These considerations prompted us to conduct a 3-year longitudinal prospective study in cognitively intact elderly individuals, who either had a diagnosis of MDD or were healthy controls, to determine if e4 and depression interacted with respect to progressive cognitive decline. We focused primarily on neurobehavioral tests sensitive to early AD and also examined the CSF total tau/Ab42 ratio, which has been linked to incident MCI/AD-related decline. Methods: 91 participants were included in this study, 60 older and with an MMSE score of at least 28 at the beginning of the 3-year longitudinal investigation. 45 participants had a diagnosis of MDD. APOE status and CSF AD biomarkers were determined at baseline and participants underwent a comprehensive neuropsychological test battery that included the Buschke Selective Reminding Test and the Boston Naming Task. Regression models examining change scores from baseline to follow-up were employed to test our hypotheses. Results: Adjusting for age and MMSE score, elderly participants with depression and carrying APOE e4 showed greater decline on average in the Boston Naming Task (p < 0.01) and a trend with high imagery performance (p = 0.05). A higher CSF total tau/Ab42 ratio was associated with decline in memory performance among depressed subjects (r =-0.45, p = 0.03, n = 23), regardless of APOE status, but not in controls. Conclusions: Our results indicate that cognitively intact depressive e4 carriers have greater decline in selective cognitive tests especially in a confrontation naming task even during a relatively short three year longitudinal period compared to controls. Additionally, increased brain AD pathology as reflected by the CSF tau/Ab42 ratio appeared to be associated with greater decline in memory performance in all depressives, regardless of APOE e4 status

Background: The APOE e4 allele, an established risk factor for AD, may act synergistically with depression to increase the risk for progressive cognitive decline and conversion to MCI/AD. However, these findings have been reported inconsistently. Methodological differences across studies, including in the definition of depression, failure to properly diagnose depression or AD, short duration of follow up, and possible inclusion of individuals with preexisting cognitive decline or MCI. These considerations prompted us to conduct a 3-year longitudinal prospective study in cognitively intact elderly individuals, who either had a diagnosis of MDD or were healthy controls, to determine if e4 and depression interacted with respect to progressive cognitive decline. We focused primarily on neurobehavioral tests sensitive to early AD and also examined the CSF total tau/Abeta42 ratio, which has been linked to incident MCI/AD-related decline. Methods: 91 participants were included in this study, age 60 and older, with an MMSE 28 at the beginning of the 3- year longitudinal investigation. 45 participants had a diagnosis of MDD. Participants underwent a comprehensive neuropsychological test battery that included the Buschke Selective Reminding Test and Boston Naming Task at baseline and annually thereafter. APOE status on all and CSFAD biomarkers on a subset of subjects were determined at baseline. Regression analyses examining neuropsych change scores (baseline to follow-up) as functions of baseline characteristics. Results: Adjusting for age and MMSE score, participants with depression and carrying. Conclusions: Our results indicate that cognitively intact depressive e4 carriers have greater decline in selective cognitive tests especially in a confrontation naming task even during a relatively short three year longitudinal period compared to controls. Additionally, increased brain AD pathology as reflected by the CSF tau/Abeta42 ratio appeared to be associated with greater decline in memory performance in all depressives, regardless of APOE e4 status

The acquired immune deficiency syndrome is characterized by the development of multiple recurrent opportunistic infections or unusual neoplasms in individuals with no prior history of immune suppression. This report summarizes the thoracic diseases encountered in such patients before after death and the role of diagnostic techniques currently used in the evaluation of thoracic disease in 15 patients with this syndrome. Efficacy of treatment was determined by correlation with postmortem findings in all patients. Pulmonary disease was present in all 15 patients and necessitated 23 transbronchial biopsies in 11 patients. Pneumocystis carinii pneumonia and cytomegalovirus pneumonia were the most common findings. Nine open lung biopsies in eight patients disclosed either Pneumocystis carinii pneumonia or Kaposi's sarcoma. Esophageal disease was present in four patients, and endoscopic evaluation demonstrated Candida esophagitis (two), esophageal Kaposi's sarcoma (one), and cytomegalovirus esophagitis and Kaposi's sarcoma (one). Mean time to death from diagnosis of acquired immune deficiency syndrome was 7.7 months, with respiratory insufficiency being the most common cause of death (9/15, 60%). Pneumocystis carinii pneumonia was successfully eradicated in 70% of the patients. Candida esophagitis was ameliorated in both patients with the disease. Unsuspected pulmonary Kaposi's sarcoma, cytomegalovirus pneumonitis, and other infectious pathogens were documented at autopsy. These data reveal that Pneumocystis carinii pneumonia and Candida esophagitis can be managed successfully in patients with acquired immune deficiency syndrome if appropriately diagnosed. The major cause of death in this series was pulmonary insufficiency, often the result of severe cytomegalovirus infection. Thoracic surgeons must continue to play an aggressive and important role in the early diagnosis and management of potentially treatable pulmonary and esophageal disease in these patients