This thesis investigated factors contributing to the high variability of observed cognitive deficits (Studies I, II, III), and reversibility of cognitive deficits (Studies III, IV), in old-age depression. Dementia-free nondepressed and depressed (unipolar; ICD-10 criteria) participants from the population-based Swedish National study on Aging and CareKungsholmen (SNAC-K) who underwent extensive neuropsychological testing formed the basis of the study samples.
Study I assessed the influence of depression severity on cognitive performance, while controlling for a range of clinical and demographic factors. Individuals with moderate/severe depression exhibited deficits in multiple cognitive domains, whereas only processing speed was affected in mild depression. Study II examined the influence of combined KIBRA (CC) and CLSTN2 (TT) risk alleles on episodic memory performance. Episodic memory deficits were only observed in individuals with both depression and the disadvantageous CC/TT allelic combination. Study III investigated the role of psychiatric history on cognitive performance in acute and remitted states of depression. Currently depressed individuals with a psychiatric inpatient history and individuals with late-onset depression performed at the lowest levels, whereas cognitive performance in individuals with self-reported recurrent unipolar depression was intermediate. Individuals with remitted unipolar depression exhibited no cognitive deficits. Physical inactivity, cumulative inpatient days, heart disease burden, and prodromal dementia modulated cognitive performance. Study IV assessed cognitive performance in different depression courses (depressed-remitted, remitted-depressed, and nondepressed-late-onset depression) longitudinally over a maximum period of 6 years. Cognitive decline was observed in all groups for multiple domains, although individuals who changed their status from nondepressed to depressed showed exacerbated cognitive decline. In remitted states, only processing speed and attention were affected. However, these deficits were modulated by benzodiazepine intake.
In sum, depression-related cognitive deficits were observed in processing speed, attention, executive function, verbal fluency (Studies I, III, IV), episodic memory (Studies I, II), and semantic memory (Study I). No depression-related deficits were observed in general knowledge, short-term memory, or spatial ability. As multiple factors were found to modulate cognitive performance in dementia-free unipolar old-age depression, and consistent with the notion that depression is a heterogeneous disorder, this may explain why patterns of cognitive deficits in depression vary between studies. Recurrence rates of depression remain high, and cognitive deficits in depression are associated with a poor prognosis and take a longer time to recover than depressive symptoms. This underscores the importance of early detection of cognitive deterioration in depression. Importantly, cognitive deficits in depression seem largely reversible. Thus, they should be regarded as treatment targets rather than as stable vulnerabilities. Combined profiles of psychiatric history, cognitive performance, and health behaviors may provide important information to individualized treatment.