| OBJECTIVES: According to the glucocorticoid cascade (Sapolsky) hypothesis, prolonged exposure to high levels of glucocorticoids may have neurotoxic effects on the brain, which may lead to deficits in learning and memory. Anxiety disorders and depression are associated with prolonged hypersecretion of glucocorticoids. However, it is unknown whether axienty or mixed anxiety/depression is associated with cognitive decline. Mixed anxiety/depression represents (i) the most severe and (ii) more persistent disorders, while analyses of risk factors suggest that (iii) compared with pure anxiety or depression, the etiology is more strongly determined by longstanding vulnerability factors. If the Sapolsky hypothesis is true, mixed anxiety/depression might have even more consequences for cognitive functioning than pure anxiety or pure depression. Furthermore, it is unknown whether anxiety plays a role in the onset of cognitive decline (etiological factor operating on normal brain functioning), or whether it speeds up an ongoing process of cognitive decline (prognostic factor operating on already deteriorating brain). Finally, an effect of anxiety or mixed anxiety/depression on cognitive functioning may be spuriously caused by other factors, independently related to both anxiety/depression and cognitive decline, for instance age, gender, socio-economic status, chronic physical illness, alcohol abuse and use of medication (benzodiazepines). The primary aim of the present study is to assess whether anxiety disorders predict cognitive decline in three different cohorts of older persons: 1) persons with normal cognitive functioning; 2) persons with mild cognitive impairment, and 3) persons with early stage dementia. Secondary aims are to test the hypothesis that mixed anxiety and depression have stronger effects on cognitive functioning than pure anxiety or pure depression, and to assess whether it is anxiety itself or some associated factor, such as use of benzodiazepines, that is implicated. METHODS: Data for the first two cohorts will be drawn from the Longitudinal Aging Study Amsterdam (LASA). LASA is a longitudinal study of autonomy and well-being in a large (N=3107) representative sample of the elderly population (>55 years). In the period from 1992 until 2002, respondents were interviewed in four cycles. Therefore, LASA covers a period of ten years and longitudinal data are available on depression, anxiety disorders, cognitive functioning and potential confounders. The study on the third cohort (persons with early stage dementia) will be carried out in the memory clinic of the Buitenamstel Municipal Health Service and the VU Medical Centre (VUMC). Out-patients who are diagnosed with (early stage) dementia will be invited to participate in the study on anxiety and depression, starting at baseline, and with annual follow-ups over a period of three years. |
