Miranda G. Dik

Depression Is Associated With Decreased 25-Hydroxyvitamin D and Increased Parathyroid Hormone Levels in Older Adults

CONTEXT Depression has incidentally been related to altered levels of 25-hydroxyvitamin D [25(OH)D] and parathyroid hormone (PTH), but this relation has never been studied systematically. OBJECTIVE To determine in a large population-based cohort whether there is an association between depression and altered 25(OH)D and PTH levels. DESIGN Population-based cohort study (Longitudinal Aging Study Amsterdam). PARTICIPANTS One thousand two hundred eighty-two community residents aged 65 to 95 years. SETTING The Netherlands. MAIN OUTCOME MEASURE Depression was measured using self-reports (Center for Epidemiologic Studies-Depression scale) and diagnostic interviews (Diagnostic Interview Schedule). Levels of 25(OH)D and PTH were assessed. Potentially confounding factors (ie, age, sex, smoking status, body mass index, number of chronic conditions, and serum creatinine concentration) and explanatory factors (ie, season of data acquisition, level of urbanization, and physical activity) were also measured. RESULTS Levels of 25(OH)D were 14% lower in 169 persons with minor depression and 14% lower in 26 persons with major depressive disorder compared with levels in 1087 control individuals (P < .001). Levels of PTH were 5% and 33% higher, respectively (P = .003). Depression severity (Center for Epidemiologic Studies Depression Scale) was significantly associated with decreased serum 25(OH)D levels (P = .03) and increased serum PTH levels (P = .008). CONCLUSION The results of this large population-based study show an association of depression status and severity with decreased serum 25(OH)D levels and increased serum PTH levels in older individuals.

Early Life Physical Activity and Cognition at Old Age

Physical activity has shown to be inversely associated with cognitive decline in older people. Whether this association is already present in early life has not been investigated previously. The association between early life physical activity and cognition was studied in 1,241 subjects aged 62-85 years, in a prospective population-based study. Physical activity between ages 15 and 25 years was asked retrospectively. The findings suggest a positive association between regular physical activity early in life and level of information processing speed at older age in men, not in women. The association could not be explained by current physical activity or other lifestyle factors. This finding supports the cognitive reserve hypothesis, and might suggest that early life physical activity may delay late-life cognitive deficits.

Insulin-like growth factor I (IGF-I) and cognitive decline in older persons

Insulin-like growth factor I (IGF-I) deficiency may be involved in cognitive deficits seen with aging, and in neurodegenerative diseases such as Alzheimers disease. The objective of this study was to investigate whether IGF-I is associated with cognitive performance and 3-year cognitive decline in 1318 subjects, aged 65-88 years. Cross-sectionally, IGF-I was directly related to information processing speed, memory, fluid intelligence, and Mini-Mental State Examination (MMSE) score, but these associations did not remain significant after adjustment for age and other factors. Analysis in quintiles of IGF-I revealed a threshold effect of low IGF-I on information processing speed, with lower speed in subjects in the lowest quintile of IGF-I (<9.4 nmol/l)(1) versus those in the other four quintiles (fully adjusted B=-0.89; 95% CI, -1.72 to -0.05). This threshold of low IGF-I was also observed for 3-year decline in information processing speed (adjusted RR=1.78; 95% CI, 1.19-2.68). In summary, this study suggests that IGF-I levels below 9.4 nmol/l are negatively associated with both the level and decline of information processing speed.

Inflammatory markers in AD and MCI patients with different biomarker profiles

OBJECTIVE The aim of this study was to demonstrate the involvement of the inflammatory proteins IL-6, ACT and CRP early in the pathology process of AD in patients with mild cognitive impairment (MCI) and AD. METHODS IL-6, ACT, CRP, Abeta42, phospho-tau (p-tau) and total tau concentrations in serum and CSF of 145 patients with probable AD and 67 patients with MCI were measured by sandwich ELISA. MCI patients were characterized as high- respectively low-risk MCI according to their Abeta42/tau risk profile. RESULTS CSF and serum CRP levels were significantly higher in MCI compared to AD patients after adjustment for age, ApoE epsilon4 genotype and cardiovascular diseases (p<0.01). This difference remained present in patients with a low-risk biomarker profile for AD after adjustment for abovementioned covariates. CSF IL-6 levels were also significantly higher in MCI patients with a low-risk CSF profile. CONCLUSIONS These findings suggest that inflammatory processes might be involved in early stages of AD, even before Abeta and tau changes are present in CSF of MCI patients.

The course of cognitive decline in older persons: results from the longitudinal aging study amsterdam.

The course of cognitive functioning in older persons was studied over a period of 6 years. The first aim was to distinguish cognitive decline as a temporary state from progressive cognitive decline. The second aim was to identify predictors which may be useful in discriminating persons with temporary cognitive decline from persons with progressive cognitive decline at an early stage. Data were derived from the Longitudinal Aging Study Amsterdam (LASA), a population-based study in the Netherlands. The results show that 18.2% of the sample of older persons showed cognitive decline over a period of 3 years. Of this group, 44% recovered from cognitive decline or stayed stable in the next 3 years. Especially older age, memory complaints and an increase of cardiovascular diseases at follow-up predict further deterioration.

Total cholesterol and oxysterols: early markers for cognitive decline in elderly?

In this prospective study we examined whether total cholesterol and the oxysterols 24S- and 27-hydroxycholesterol were related to cognitive performance and rate of cognitive decline in elderly, and whether these associations were modified by ApoE epsilon 4. Data were collected during 6 years of follow-up as part of the Longitudinal Aging Study Amsterdam (N=1181, age >or=65 years), and analyzed using generalized estimating equations. Cognitive performance was measured with the mini-mental state examination (general cognition), the auditory verbal learning test (memory) and the coding task (information processing speed). Lower cholesterol at baseline was negatively associated with both general cognition (p=.012) and information processing speed (p=.045). ApoE modified the association between cholesterol and cognitive decline, and the association between the ratio of 27-hydroxycholesterol to cholesterol and cognitive functioning. In ApoE epsilon 4 carriers, lower cholesterol was related to a higher rate of decline on information processing speed (p=.006), and a higher ratio of 27-hydroxycholesterol to cholesterol was related to a lower level of general performance (p=.002) and memory functioning (p=.045). The results implicate that lower total cholesterol may be considered as a frailty marker, predictive of lower cognitive functioning in elderly.

Homocysteine and inflammation: predictors of cognitive decline in older persons?

The aim of the current study was to examine the association between homocysteine and 6-year cognitive decline, and the modifying role of the inflammatory markers Interleukin-6 (IL-6), C-reactive protein (CRP) and alpha-1-antichymotrypsin (ACT). Data were collected within the Longitudinal Aging Study Amsterdam (ages >or=65 years) and analyzed using multiple longitudinal regression models (N=1257 of whom N=1076 had longitudinal data). Cognition was measured with the Mini-Mental State Examination (general cognition), Auditory Verbal Learning Test (memory), Coding Task (information processing speed) and Raven Coloured Progressive Matrices (fluid intelligence). Higher homocysteine at baseline was negatively associated with prolonged lower cognitive functioning and a faster rate of decline in information processing speed and fluid intelligence. The negative association between higher homocysteine and immediate recall was strongest in persons with a high level of IL-6. Only in the highest tertile of CRP, higher homocysteine was negatively associated with retention. In the middle tertile of ACT, higher homocysteine was associated with lower information processing speed and faster decline. Both in the lower and middle tertile of CRP, higher homocysteine was associated with a faster rate of decline in information processing speed. The results implicate that a combination of both risk factors may be used as a marker for cognitive impairment.

The Impact of Change in Cognitive Functioning and Cognitive Decline on Disability, Well-Being, and the Use of Healthcare Services in Older Persons

The study investigated the impact of change in cognitive functioning and cognitive decline on disability, well-being, and the use of healthcare services among older persons in the Longitudinal Aging Study Amsterdam (LASA). Data were collected from 1,349 subjects, aged 65–85 years, who had scores of 24 and higher on the Mini-Mental State Examination (MMSE) at baseline, over a period of 6 years in three waves. The results indicate that cognitive decline and changes in cognitive functioning in older persons who were either not impaired or only mildly cognitively impaired at baseline have an impact on disability, well-being, and the use of healthcare services. With the aging of the population, the number of persons with cognitive impairment is likely to increase, and appropriate services should be available to them.

Late-Life Depression, Cortisol, and the Metabolic Syndrome

OBJECTIVES High-cortisol levels in depressed persons could possibly give rise to the metabolic syndrome. This study investigated cross-sectionally whether depression and high-cortisol levels increased the odds of metabolic syndrome in an older community-based sample. METHODS In 1,212 participants, aged > or =65 years, enrolled in the Longitudinal Aging Study Amsterdam, depression (major [1-month diagnosis] or subthreshold [no 1-month diagnosis, but symptoms]), metabolic syndrome (modified Adult Treatment Panel III criteria), and free cortisol index (total serum cortisol/cortisol binding globulin) were assessed. RESULTS Major depression was not associated with the metabolic syndrome (odds ratio [OR] = 1.16, 95% confidence interval [CI] = 0.54-2.49), but subthreshold depression was associated with a decreased odds (OR = 0.55, 95% CI = 0.37-0.82). Persons with higher levels of free cortisol index showed a higher odds of metabolic syndrome (OR per standard deviation increase = 1.21, 95% CI = 1.06-1.39). CONCLUSIONS As persons with high-cortisol levels more often had metabolic syndrome, hypercortisolemia within depressed persons may increase the risk of metabolic syndrome.

Effects of Gender and Age on the Association of Apolipoprotein E ε4 with Bone Mineral Density, Bone Turnover and the Risk of Fractures in Older People*

Abstract: The aim of this study was to examine whether the presence of apolipoprotein E ε4 (ApoE ε4) is associated with a lower bone mineral density (BMD), lower quantitative ultrasound (QUS) measurements, higher bone turnover and fracture risk, and whether these relations are modified by gender and age. A total of 1406 elderly men and women (≥65 years) of the Longitudinal Aging Study Amsterdam (LASA) participated in this study. In all participants, QUS measurements were assessed, as well as serum osteocalcin (OC) and urine deoxypyridinolin (DPD/Cr urine). Follow-up of fractures was done each three months. In a subsample (n = 604), total body bone mineral content (BMC) and BMD of the hip and lumbar spine were measured. In addition, prevalent vertebral deformities were identified on radiographs. In women, the presence of ApoE ε4 was associated with significantly lower femoral neck BMD (g/cm2; mean ± SEM; ε4+, 0.64 ± 0.01 vs. ε4−, 0.67 ± 0.01; p= 0.04), lower trochanter BMD (g/cm2; mean ± SEM; ε4+, 0.58 ± 0.01 vs. ε4–, 0.61 ± 0.01; p= 0.01) and lower total body BMC (g; mean ± SEM; ε4+, 1787 ± 40.0 vs. ε4–, 1863 ± 23.8; p= 0.04). Women with ApoE ε4 also had a higher risk of severe vertebral deformities (OR=2.78; 95%CI: 1.21–6.34). In men, the associations between ApoE status and both hip BMD and QUS depended on age. Only among the younger men (65–69 years) was the presence of ApoE ε4 associated with lower BMD values. Bone markers and fractures were not associated with ApoE ε4 in either women, or men. In conclusion, this large community-based study confirms the importance of ApoE ε4 as a possible genetic risk factor related to BMD and vertebral deformities and demonstrates that its effect is gender related, and depends on age in men only.