A bi-factor model of the Montgomery Åsberg depression rating scale and future cognitive impairments in older adults: A 6-year follow-up study.

Depression has been found to be associated with cognitive decline. This study evaluated the association of general depressive symptoms and motivational-related symptoms with cognitive impairment 6 years later and to explore the role of potential underlying mechanisms. In 2690 cognitively healthy persons aged ≥60 from the Swedish National study on Aging and Care in Kungsholmen (SNAC-K) depressive symptoms were derived from the Montgomery Åsberg Depression Rating Scale (MADRS). Cognitive performance was assessed at baseline and 6 years later in 1810 persons with the Mini Mental State Examination (global cognition), Digit Span Forward (short-term memory), Digit Span Backward (working memory), Clock-test (visuospatial construction), and the 5-item test (immediate and delayed recall). Bi-factor analysis on the MADRS yielded a General Depression factor and an unrelated Motivational factor. After adjusting for demographics, the General Depression factor was only associated with 6-year impairment in delayed recall (OR (95% CI): 1.18 (1.04-1.34)). This association was no longer significant after adjusting for demographics, cardiovascular risk, lifestyle factors and medication use. The Motivational factor was not significantly associated with future cognitive impairments after adjusting for demographics. Concluding, almost all associations of general depressive symptoms and motivational-related symptoms with future cognitive impairments appeared to be confounded by demographics. Only the association of general depressive symptoms with future memory impairments appeared to be explained by a combination of demographics, cardiovascular risk, lifestyle and medication use.

Relationships Between Aerobic Fitness Levels and Cognitive Performance in Swedish Office Workers.

Objectives: Aerobic exercise influence cognition in elderly, children, and neuropsychiatric populations. Less is known about the influence of aerobic exercise in healthy samples (particularly working age), and of different fitness levels on cognition. Two hypotheses were posed: (1) low fitness levels, compared to moderate and high, will be related to poorer cognitive performance, and (2) breakpoints for the beneficial relationship between VO2 and cognition will be observed within the moderate-to-high fitness span. Design and Methods: The sample consisted of n=362 office workers. A submaximal cycle ergometer test estimated maximal oxygen consumption (VO2max, mL·kg-1·min-1). Based on estimated VO2max participants were split into tertiles; low (n = 121), moderate (n = 119), and high (n = 122). A cognitive test battery (9 tests), assessed processing speed, working memory, executive functions and episodic memory. Results: Both hypotheses were confirmed. Groups of moderate (≈40) and high (≈49) fitness outperformed the group of low (≈31) fitness for inhibition and episodic recognition, whereas no significant differences between moderate and high fitness were observed (ANCOVAs). Breakpoints between benefits fromVO2max for inhibition and recognition were estimated to ≈44/43 mL·kg-1·min-1 (multivariate broken line regressions). Conclusions: Results suggest that it is conceivable to expect a beneficial relationship between VO2max and some cognitive domains up to a certain fitness level. In a sample of healthy office workers, this level was estimated to 44 mL·kg-1·min-1. This has implications on organizational and societal levels; where incentives to improve fitness levels from low to moderate could yield desirable cognitive and health benefits in adults.

Cognitive performance in unipolar old-age depression: a longitudinal study.

OBJECTIVE: Previous studies on cognitive deficits in acute and remitted states of old-age depression have shown mixed findings. The episodic nature of depression makes repeated assessment of cognitive performance important in order to address reversibility and stability of cognitive deficits. METHODS: Dementia-free older participants (≥60 years) from the population-based Swedish National Study on Aging and Care in Kungsholmen who completed neuropsychological testing at baseline (T1) and follow-up (T2) formed the basis of the study sample. Participants were grouped according to depression status at T1 and T2: depressed-remitted (n = 32), remitted-depressed (n = 45), and nondepressed-depressed (n = 29). These groups were compared with a group of randomly selected and matched (age, gender, education, and follow-up time) healthy controls (n = 106) over a period of maximum 6 years. RESULTS: Mixed ANCOVAs, controlling for age and gender, revealed depression-related deficits for processing speed, attention, executive function, and category fluency. In remitted states, only processing speed and attention were affected. However, these deficits were attenuated after exclusion of persons using benzodiazepine medications. A general pattern of cognitive decline was observed across all groups for processing speed, executive function, category fluency, and episodic and semantic memory; persons transitioning from a nondepressed to depressed state tended to show exacerbated cognitive decline. CONCLUSIONS: The results support the notion that cognitive deficits in depression may be more transient than stable. Consequently, cognitive deficits in depression might be regarded as potential treatment targets rather than stable vulnerabilities. As such, repeated assessment of cognitive functioning may provide an additional marker of treatment response.

Effects of psychiatric history on cognitive performance in old-age depression.

Cognitive deficits in old-age depression vary as a function of multiple factors; one rarely examined factor is long-term psychiatric history. We investigated effects of psychiatric history on cognitive performance in old-age depression and in remitted persons. In the population-based Swedish National Study on Aging and Care in Kungsholmen study, older persons (≥60 years) without dementia were tested with a cognitive battery and matched to the Swedish National Inpatient Register (starting 1969). Participants were grouped according to current depression status and psychiatric history and compared to healthy controls (n = 96). Group differences were observed for processing speed, attention, executive functions, and verbal fluency. Persons with depression and psychiatric inpatient history (n = 20) and late-onset depression (n = 49) performed at the lowest levels, whereas cognitive performance in persons with self-reported recurrent unipolar depression (n = 52) was intermediate. Remitted persons with inpatient history of unipolar depression (n = 38) exhibited no cognitive deficits. Heart disease burden, physical inactivity, and cumulative inpatient days modulated the observed group differences in cognitive performance. Among currently depressed persons, those with inpatient history, and late onset performed at the lowest levels. Importantly, remitted persons showed no cognitive deficits, possibly reflecting the extended time since the last admission (m = 15.6 years). Thus, the present data suggest that cognitive deficits in unipolar depression may be more state- than trait-related. Information on profiles of cognitive performance, psychiatric history, and health behaviors may be useful in tailoring individualized treatment.

Interactive effects of KIBRA and CLSTN2 polymorphisms on episodic memory in old-age unipolar depression.

The KIBRA (rs17070145) C-allele and the CLSTN2 (rs6439886) T-allele have both been associated with poorer episodic memory performance. Given that episodic memory is affected in depression, we hypothesized that the combination of these risk alleles would be particularly detrimental to episodic memory performance in depressed persons. In the population-based SNAC-K study, 2170 participants (≥ 60 years) without dementia (DSM-IV criteria) and antidepressant pharmacotherapy were clinically examined and diagnosed following ICD-10 criteria for unipolar depression, and genotyped for KIBRA and CLSTN2. Participants were categorized according to unipolar depression status (yes, no) and genotype combinations (KIBRA: CC, any T; CLSTN2: TT, any C). Critically, a three-way interaction effect showed that the CC/TT genotype combination was associated with poorer episodic recall and recognition performance only in depressed elderly persons, with depressed CC/TT carriers consistently performing at the lowest level. This finding supports the view that effects of genetic polymorphisms on cognitive functioning may be most easily disclosed at suboptimal levels of cognitive ability, such as in old-age depression.

Genetic effects on old-age cognitive functioning: a population-based study.

Associations between genotypes and cognitive outcomes may provide clues as to which mechanisms cause individual differences in old-age cognitive performance. We investigated the effects of five polymorphisms on cognitive functioning in a population-based sample of 2,694 persons without dementia (60-102 years). A structural equation model (SEM) was fit to the cognitive data, yielding five specific latent factors (perceptual speed, episodic memory, semantic memory, category fluency, and letter fluency), as well as a global cognitive factor. These factors showed the expected associations with chronological age. Genotyping was performed for five single-nucleotide polymorphisms that have been associated with cognitive performance: APOE (rs429358), COMT (rs4680), BDNF (rs6265), KIBRA (rs17070145), and CLSTN2 (rs6439886). After controlling for age, gender, and education, as well as correcting for multiple comparisons, we observed negative effects of being an APOE ε4 carrier on episodic memory and perceptual speed. Furthermore, being a CLSTN2 TT carrier was associated with poorer semantic memory. For the global factor, the same pattern of results was observed. In addition, being a BDNF any A carrier was associated with better cognitive performance. Also, older age was associated with stronger genetic effects of APOE on global cognition. However, this interaction effect was partly driven by the presence of preclinical dementia cases in our sample. Similarly, excluding future dementia cases attenuated the effects of APOE on episodic memory and global cognition, suggesting that part of the effects of APOE on old-age cognitive performance may be driven by dementia-related processes.