To examine the 1-month prevalence of generalized anxiety disorder (GAD) according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), Diagnostic and Statistical Manual of Mental, Fifth Edition (DSM-V), and International Classification of Diseases, Tenth Revision (ICD-10), and the overlap between these criteria, in a population sample of 75-year-olds. We also aimed to examine comorbidity between GAD and other psychiatric diagnoses, such as depression.
During 2005-2006, a comprehensive semistructured psychiatric interview was conducted by trained nurses in a representative population sample of 75-year-olds without dementia in Gothenburg, Sweden (N = 777; 299 men and 478 women). All psychiatric diagnoses were made according to DSM-IV. GAD was also diagnosed according to ICD-10 and DSM-V.
The 1-month prevalence of GAD was 4.1% (N = 32) according to DSM-IV, 4.5% (N = 35) according to DSM-V, and 3.7% (N = 29) according to ICD-10. Only 46.9% of those with DSM-IV GAD fulfilled ICD-10 criteria, and only 51.7% and 44.8% of those with ICD-10 GAD fulfilled DSM-IV/V criteria. Instead, 84.4% and 74.3% of those with DSM-IV/V GAD and 89.7% of those with ICD-10 GAD had depression. Also other psychiatric diagnoses were common in those with ICD-10 and DSM-IV GAD. Only a small minority with GAD, irrespective of criteria, had no other comorbid psychiatric disorder. ICD-10 GAD was related to an increased mortality rate.
While GAD was common in 75-year-olds, DSM-IV/V and ICD-10 captured different individuals. Current definitions of GAD may comprise two different expressions of the disease. There was greater congruence between GAD in either classification system and depression than between DSM-IV/V GAD and ICD-10 GAD, emphasizing the close link between these entities.
It is well established that there is an association between the apolipoprotein E (APOE) e4 allele (APOE*E4) and Alzheimer's disease. It is less clear whether there is also an association with geriatric depression. We examined the relationship between APOE*E4 and 5-year incidence of depression in a Swedish population-based sample of older adults without dementia and excluding older adults who developed dementia within 4 years after the diagnosis of depression.
In 2000-2001, 839 women and men (age range, 70-92 years; mean age, 73.8 years) free from dementia and depression underwent neuropsychiatric and neuropsychological examinations and genotyping of the APOE*E4 allele. Follow-up evaluations were conducted in 2005 and 2009.The association between APOE*E4 allele and 5-year incidence of depression was examined, while avoiding possible confounding effects of clinical or preclinical dementia by excluding participants who had dementia at study entry, subsequently developed dementia during the 9-year follow-up period, or had a decline in Mini-Mental State Examination score of =5 points.
Among subjects without depression at study entry and without dementia or significant cognitive decline during the subsequent 9 years, APOE*E4 was prospectively associated with more severe depressive symptoms (b = 1.56, p = .007), incident minor depression (odds ratio = 1.99 [confidence interval = 1.11-3.55], p = .020), and any depression (odds ratio = 1.75 [confidence interval = 1.01-3.03], p = .048).
The presence of the APOE*E4 allele predicted future depression in this Swedish population study, even after excluding depressed individuals who later developed dementia, suggesting that the APOE*E4 allele could potentially identify people at high risk for clinically significant depression.
Comment In: Biol Psychiatry. 2015 Nov 15;78(10):670-126497282
Overweight and obesity in mid- and late-life may increase risk for dementia, whereas a decline in body weight or body mass index (BMI) and underweight in years preceding a clinical dementia diagnosis are also associated with dementia. Little is known about the modifying effect of the APOE genotype, a major susceptibility gene for Alzheimer's disease (AD), on the BMI-dementia adult life course trajectory.
We evaluated the exposure, BMI, in relationship to the outcome, clinical dementia, over 37 years, considering the effect modification of the APOE ?4 allele.
The Prospective Population Study of Women (PPSW) in Sweden is a systematic sample of 1462 women born 1908, 1914, 1918, 1922, and 1930 and aged 38-60 years at baseline. Examinations occurred in 1968, 1974, 1980, 1992, 2000, and 2005; 559 women had information on dementia, BMI, and APOE ?4 allele status, in addition to covariates. Statistical analyses were conducted using mixed effects regression models.
Trajectories of BMI over 37 years differed by APOE ?4 allele status. While women gained BMI similarly from mid-life to age 70 years, women with at least one APOE ?4 allele experienced BMI decline more quickly after age 70 years compared to women without an APOE ?4 allele. However, upon stratifying the sample by dementia occurrence, it appeared that dementia drove the overall BMI-trajectory. There was a main effect of age, interactions of age by APOE ?4 allele status, and age by presence versus absence of dementia.
Women with similar average BMI at mid-life exhibited different BMI trajectories in relation to dementia occurrence. In addition, the pattern of BMI decline in late-life differed on the basis of APOE ?4 allele possession. Thus, these data suggest roles for both dementia- and APOE-associated changes in BMI during the adult life course.
Level of adiposity is linked to dementia in epidemiological studies. Overweight and obesity in mid- and late-life may increase risk for dementia, whereas decline in body weight or body mass index (BMI) and underweight in years preceding and at the time of a dementia diagnosis may also relate to dementia. Longitudinal studies with sufficient follow-up are necessary to estimate trajectories that allow better understanding of the relationship between adiposity indices and dementia over the life course. We evaluated the natural history of BMI in relationship to clinical dementia over 37 years in the Prospective Population Study of Women (PPSW) in Sweden. PPSW is a systematic sample of 1462 women born 1908, 1914, 1918, 1922, and 1930 and aged 38-60 years at baseline. Examinations occurred in 1968, 1974, 1980, 1992, 2000, and 2005. Statistical analyses were conducted using mixed effects regression models. Trajectories of BMI over 37 years as a function of age differed between women who did versus did not develop dementia. Women developing dementia evidenced a lesser increase in BMI from age 38 to 70 years. After age 70, the BMI slope decreased similarly (no "accelerated decline") irrespective of dementia status. A lower BMI before and during dementia onset was observed. Women with similar BMI at mid-life exhibited a different pattern of BMI change as they approached late-life that was related to dementia onset. BMI may be a potential marker of dementia-related neuropathologies in the brain. Dementia is related to a common risk factor, BMI, from mid-to late-life.
This study aimed to examine the long-term effect of high blood pressure (systolic blood pressure, diastolic blood pressure, pulse pressure, and mean arterial pressure) on white matter lesions and to study changes in different blood pressure components in relation to white matter lesions. A representative population of women was examined in 1968 and re-examined in 1974, 1980, 1992, and 2000. The presence and severity of white matter lesions on computed tomography were rated by a visual rating scale in 1992 and 2000 in 539 women. Systolic and diastolic blood pressures were measured at all of the examinations. We found that presence and severity of white matter lesions in 1992/2000 were associated with higher diastolic blood pressure and mean arterial pressure at each examination but not with systolic blood pressure and pulse pressure. Odds ratios (95% CIs) for the presence of white matter lesions per 10-mm Hg increase in diastolic pressure were 1.4 (1.0 to 1.9) in 1968, 1.3 (1.0 to 1.8) in 1974, 1.4 (1.1 to 1.9) in 1980, and 1.3 (1.0 to 1.6) in 1992 after adjustment for confounders. The presence of white matter lesions was also associated with a 24-year increase in diastolic pressure (>10 mm Hg), systolic pressure (>40 mm Hg), pulse pressure (>24 mm Hg), and mean arterial pressure (>6 mm Hg; odds ratios [95% CIs]: 2.6 [1.3 to 5.1] for diastolic pressure; 2.0 [1.2 to 3.4] for systolic pressure; 1.8 [1.1 to 2.7] for pulse pressure; and 2.2 [1.4 to 3.4] for mean arterial pressure). Our findings suggest that lowering high diastolic blood pressure and preventing large increases in systolic and diastolic blood pressures may have a protective effect on white matter lesions.
Higher midlife blood pressure increases risk for dementia. To further understand the relation between blood pressure and dementia, it is necessary to examine evolution of blood pressure from midlife to late life. We examined blood pressure trajectories using linear mixed models in a representative sample of middle-aged women (N=1462) who were followed from 1968-1969 until 2005-2006 with comprehensive medical and neuropsychiatric examinations. Dementia was diagnosed according to established criteria. Among those not treated with antihypertensives, higher systolic blood pressure at baseline but not blood pressure trajectories from 1968 to 1992 was associated with dementia and Alzheimer disease. Those with history of antihypertensive treatment had higher baseline systolic blood pressure than those who were never treated. In this group, those who developed dementia and Alzheimer disease had lower baseline systolic blood pressure and steeper increase in systolic blood pressure from 1968 to 1992 than those who did not. A steeper decline in systolic blood pressure during the later part of the study was observed in those who developed dementia regardless of antihypertensive treatment. The latter association was attenuated or disappeared when adjusting for body mass index. The association between blood pressure and dementia is complex and influenced by antihypertensive treatment. The findings emphasize the importance of detecting increased blood pressure in midlife and controlling blood pressure in those treated. Whether the trajectory of blood pressure is a risk factor or part of the clinical course of dementia needs to be elucidated.
To determine whether calcium supplementation is associated with the development of dementia in women after a 5-year follow-up.
This was a longitudinal population-based study. The sample was derived from the Prospective Population Study of Women and H70 Birth Cohort Study in Gothenburg, Sweden, and included 700 dementia-free women aged 70-92 years. At baseline in 2000-2001, and at follow-up in 2005-2006, the women underwent comprehensive neuropsychiatric and somatic examinations. A CT scan was performed in 447 participants at baseline. Information on the use and dosage of calcium supplements was collected. Dementia was diagnosed according to DSM-III-R criteria.
Women treated with calcium supplements (n = 98) were at a higher risk of developing dementia (odds ratio [OR] 2.10, 95% confidence interval [CI] 1.01-4.37, p = 0.046) and the subtype stroke-related dementia (vascular dementia and mixed dementia) (OR 4.40, 95% CI 1.54-12.61, p = 0.006) than women not given supplementation (n = 602). In stratified analyses, calcium supplementation was associated with the development of dementia in groups with a history of stroke (OR 6.77, 95% CI 1.36-33.75, p = 0.020) or presence of white matter lesions (OR 2.99, 95% CI 1.28-6.96, p = 0.011), but not in groups without these conditions.
Calcium supplementation may increase the risk of developing dementia in elderly women with cerebrovascular disease. Because our sample was relatively small and the study was observational, these findings need to be confirmed.
Cites: N Engl J Med. 2003 Mar 27;348(13):1215-2212660385
We have shown that high mid-life central adiposity may increase the risk for dementia after 32 years. Leptin, an adipose tissue hormone, is correlated with adiposity measures and may contribute to a better etiological understanding of the relationship between high adiposity and dementia. We explored the relationship between serum leptin in mid-life and dementia, which is a late-life outcome.
A longitudinal cohort study, the Prospective Population Study of Women, in Gothenburg, Sweden, includes a representative sample of 1462 women followed from mid-life ages of 38 to 60 years to late-life ages of 70 to 92 years. Women were examined in 1968, 1974, 1980, 1992, and 2000 using neuropsychiatric, anthropometric, clinical, and other measurements. Serum leptin was measured on samples collected at the 1968 baseline examination, after storage at -20°C for 29 years. Cox proportional hazards regression models estimated incident dementia risk by baseline leptin. Logistic regression models related leptin levels to dementia among surviving participants 32 years later. All models were adjusted for multiple potential confounders.
Mid-life leptin was not related to dementia risk using Cox or logistic regression models. This was observed despite positive baseline correlations between leptin and adiposity measures, and given our previous report of high mid-life waist-to-hip ratio being related to a twofold higher dementia risk.
Leptin is not a mid-life marker of late-life dementia risk in this population sample of Swedish women born between 1908 and 1930.
We described longitudinal changes of movement performance in a population-based sample of women followed from age 70 to 78. We also studied the cross-sectional relationships between medical conditions and movement performance at baseline, and longitudinal relationships between baseline medical conditions and changes of movement performance. Two hundred and thirty-four women aged 70 years participated in the baseline study, and 88 women participated in a follow-up study 8 years later. Movement performance was measured by an optoelectronic test, the postural-locomotor-manual (PLM) test, which objectively and precisely measures the subject's mobility of lower and upper extremities. Information on medical conditions including selected diseases and symptoms were obtained by self-report and/or by physical examination. Movement time (MT), an indicator of the overall movement performance of the PLM test, increased over 8 years. This change was mainly related to prolonged duration of the locomotor phase (walking forward), but not to the duration of the manual phase (goal-directed arm reaching). At baseline, poor PLM performance was related to hypertension, orthostatic hypotension, cerebrovascular diseases, chronic bronchitis, depression, arthritis, dizziness, chest pain, dyspnea, joint problems, leg pain, tiredness, number of diseases and number of symptoms at baseline. Increased MT during follow-up was associated with arthritis and dyspnea at baseline, and newly developed diseases during follow-up. Our study results indicated that 70-year-old women had a general slowing of their movement performance over 8 years. Age-related decrements of movement performance were more striking in the lower extremities than in the upper extremities. Arthritis and dyspnea at baseline, and incident diseases during follow-up were related to this age-related decline of movement performance.
Long-standing psychological distress increases the risk of dementia, especially Alzheimer's disease. The present study examines the relationship between midlife psychological distress and late-life brain atrophy and white matter lesions (WMLs), which are common findings on neuroimaging in elderly subjects.
A population-based sample of 1462 women, aged 38 to 60 years, was examined in 1968, with subsequent examinations in 1974, 1980, 1992, and 2000. Computed tomography (CT) of the brain was done in 379 survivors in 2000, and of those, 344 had responded to a standardized question about psychological distress in 1968, 1974, and 1980. WMLs, cortical atrophy, and central atrophy (ventricular sizes) were measured at CT scans.
Compared with women reporting no distress, those reporting frequent or constant distress at one examination or more (in 1968, 1974, and 1980) more often had moderate-to-severe WMLs (multiadjusted odds ratio = 2.39, 95% confidence interval = 1.16-4.92) and moderate-to-severe temporal lobe atrophy (multiadjusted odds ratio = 2.51, 95% confidence interval = 1.04-6.05) on brain CT in 2000. Frequent/constant distress was also associated with central brain atrophy, that is, higher bicaudate ratio, higher cella media ratio, and larger third-ventricle width.
Long-standing psychological distress in midlife increases risks of cerebral atrophy and WMLs on CT in late life. More studies are needed to confirm these findings and to determine potential neurobiological mechanisms of these associations.