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To determine whether death ideation in late life is associated with markers of elevated risk for suicide, or reflects normal psychological processes in later life.
Population based cross sectional study in Gothenburg, Sweden.
The sample consists of 345 men and women aged 85 (born 1901-02) and living in Gothenburg, Sweden.
Main Outcome Measures
The Paykel Scale measured the most severe level of suicidality over an individual’s lifetime. Other key measures were severity of depression and anxiety and frequency of death/suicidal ideation over the previous month.
Latent class analysis revealed distinct groups of older adults who reported recent death ideation. Recent death ideation did not occur apart from other risk factors for suicide; instead individuals reporting recent death ideation also reported either 1) recent high levels of depression and anxiety, or 2) more distant histories of serious suicidal ideation (indicative of worst point severity of suicidal ideation)—both of which elevate risk for eventual suicide.
Our results indicate a heterogeneous presentation of older adults who report death ideation, with some presenting with acute distress and suicidal thoughts, and others presenting with low distress but histories of serious suicidal ideation. The presence of death ideation is associated with markers of increased risk for suicide, including “worst point” active suicidal ideation.
PMCID: PMC3473151  PMID: 23567393
suicide; depression; anxiety; suicidal ideation; risk assessment
2.  Coordinated Analysis of Age, Sex, and Education Effects on Change in MMSE Scores 
We describe and compare the expected performance trajectories of older adults on the Mini-Mental Status Examination (MMSE) across six independent studies from four countries in the context of a collaborative network of longitudinal studies of aging. A coordinated analysis approach is used to compare patterns of change conditional on sample composition differences related to age, sex, and education. Such coordination accelerates evaluation of particular hypotheses. In particular, we focus on the effect of educational attainment on cognitive decline.
Regular and Tobit mixed models were fit to MMSE scores from each study separately. The effects of age, sex, and education were examined based on more than one centering point.
Findings were relatively consistent across studies. On average, MMSE scores were lower for older individuals and declined over time. Education predicted MMSE score, but, with two exceptions, was not associated with decline in MMSE over time.
A straightforward association between educational attainment and rate of cognitive decline was not supported. Thoughtful consideration is needed when synthesizing evidence across studies, as methodologies adopted and sample characteristics, such as educational attainment, invariably differ.
PMCID: PMC3693608  PMID: 23033357
Cognitive; Coordinated Analysis; Education; Longitudinal; Mental Status Exam; Meta-analysis; Mixed Model
3.  Personality in women and associations with mortality: a 40-year follow-up in the Population Study of Women in Gothenburg 
BMC Women's Health  2014;14:61.
The question of whether personality traits influence health has long been a focus for research and discussion. Therefore, this study was undertaken to examine possible associations between personality traits and mortality in women.
A population-based sample of women aged 38, 46, 50 and 54 years at initial examination in 1968–69 was followed over the course of 40 years. At baseline, 589 women completed the Cesarec-Marke Personality Schedule (the Swedish version of the Edwards Personal Preference Schedule) and the Eysenck Personality Inventory. Associations between personality traits and mortality were tested using Cox proportional hazards models.
No linear associations between personality traits or factor indices and mortality were found. When comparing the lowest (Q1) and highest quartile (Q4) against the two middle quartiles (Q2 + Q3), the personality trait Succorance Q1 versus Q2 + Q3 showed hazard ratio (HR) = 1.37 (confidence interval (CI) = 1.08-1.74), and for the factor index Aggressive non-conformance, both the lowest and highest quartiles had a significantly higher risk of death compared to Q2 + Q3: for Q1 HR = 1.32 (CI = 1.03-1.68) and for Q4 HR = 1.36 (CI = 1.06-1.77). Neither Neuroticism nor Extraversion predicted total mortality.
Personality traits did not influence long term mortality in this population sample of women followed for 40 years from mid- to late life. One explanation may be that personality in women becomes more circumscribed due to the social constraints generated by the role of women in society.
PMCID: PMC4027992  PMID: 24779414
Personality traits; Secular trends; Population-based cohort; Women; Longevity
4.  Diabetes and the brain: issues and unmet needs 
Neurological Sciences  2014;35(7):995-1001.
Diabetes mellitus (DM) is associated with an increased risk of mild cognitive impairment, dementia and stroke. The association between DM and dementia appears to be stronger for vascular cognitive impairment than for Alzheimer’s disease, suggesting cerebrovascular disease may be an important factor in cognitive impairment in DM. Although the exact mechanisms by which DM affects the brain remain unclear, changes to brain vasculature, disturbances of cerebral insulin signaling, insulin resistance, glucose toxicity, oxidative stress, accumulation of advanced glycation end products, hypoglycemic episodes, and alterations in amyloid metabolism may all be involved. Cognitive impairment and dementia associated with DM may also be mediated via vascular risk factors, in particular brain ischemia, the occurrence of which can have an additive or synergistic effect with concomitant neurodegenerative processes. To date, no drug has been approved for the treatment of vascular dementia and there are no specific pharmacological treatments for preventing or reducing cognitive decline in patients with DM. Most focus has been on tighter management of vascular risk factors, although evidence of reduced cognitive decline through reducing blood pressure, lipid-lowering or tighter glycemic control is inconclusive. Tailored, multimodal therapies may be required to reduce the risk of cognitive dysfunction and decline in patients with DM. The use of pleiotropic drugs with multimodal mechanisms of action (e.g., cerebrolysin, Actovegin) may have a role in the treatment of cognitive dysfunction and their use may warrant further investigation in diabetic populations.
PMCID: PMC4064119  PMID: 24777546
Diabetes; Cognitive impairment; Vascular dementia; Stroke
5.  Functional disability and death wishes in older Europeans: results from the EURODEP concerted action 
Physical illness has been shown to be a risk factor for suicidal behaviour in older adults. The association between functional disability and suicidal behaviour in older adults is less clear. The aim of this study was to examine the relationship between functional disability and death wishes in late life.
Data from 11 population studies on depression in persons aged 65 and above were pooled, yielding a total of 15,890 respondents. Level of functional disability was trichotomised (no, intermediate, high). A person was considered to have death wishes if the death wish/suicidal ideation item of the EURO-D scale was endorsed. Odds ratios for death wishes associated with functional disability were calculated in a multilevel logistic regression model.
In total, 5 % of the men and 7 % of the women reported death wishes. Both intermediate (OR 1.89, 95 % CI 1.42; 2.52) and high functional disability (OR 3.22, 95 % CI 2.34; 4.42) were associated with death wishes. No sex differences could be shown. Results remained after adding depressive symptoms to the model.
Functional disability was independently associated with death wishes in older adults. Results can help inform clinicians who care for older persons with functional impairment.
Electronic supplementary material
The online version of this article (doi:10.1007/s00127-014-0840-1) contains supplementary material, which is available to authorized users.
PMCID: PMC4143593  PMID: 24554123
Death wishes; Functional disability; Chronic conditions; Depressive symptoms; Late life
6.  A Randomised, Double-Blind, Placebo-Controlled Trial of Actovegin in Patients with Post-Stroke Cognitive Impairment: ARTEMIDA Study Design 
No drug treatment to date has shown convincing clinical evidence of restoring cognitive function or preventing further decline after stroke. The ongoing ARTEMIDA study will evaluate the efficacy and safety of Actovegin for the symptomatic treatment of post-stroke cognitive impairment (PSCI) and will explore whether Actovegin has any disease-modifying effect by assessing whether any changes are sustained after treatment.
ARTEMIDA is a 12-month, multicentre trial in patients (planned a total of 500, now recruited) with cognitive impairment following ischaemic stroke. The study consists of a baseline screening (≤7 days after stroke), after which eligible patients are randomised to Actovegin (2,000 mg/day for up to 20 intravenous infusions followed by 1,200 mg/day orally) or placebo for a 6-month double-blind treatment period. Patients will be followed up for a further 6 months, during which time they will be treated in accordance with standard clinical practice. The primary study endpoint is change from baseline in the Alzheimer's Disease Assessment Scale, cognitive subscale, extended version. Secondary outcomes include: Montreal Cognitive Assessment; dementia diagnosis (ICD-10); National Institutes of Health Stroke Scale; Barthel Index; EQ-5D; Beck Depression Inventory, version II, and safety.
There is a clear need for effective treatments for PSCI. ARTEMIDA should provide important insights into the use of a novel drug therapy for PSCI.
PMCID: PMC3919431  PMID: 24516413
Stroke; Vascular dementia; Cognitive impairment; Pharmacotherapy; Actovegin

7.  Hormone therapy and Alzheimer disease dementia 
Neurology  2012;79(18):1846-1852.
Observational studies suggest reduced risk of Alzheimer disease (AD) in users of hormone therapy (HT), but trials show higher risk. We examined whether the association of HT with AD varies with timing or type of HT use.
Between 1995 and 2006, the population-based Cache County Study followed 1,768 women who had provided a detailed history on age at menopause and use of HT. During this interval, 176 women developed incident AD. Cox proportional hazard models evaluated the association of HT use with AD, overall and in relation to timing, duration of use, and type (opposed vs unopposed) of HT.
Women who used any type of HT within 5 years of menopause had 30% less risk of AD (95% confidence interval 0.49–0.99), especially if use was for 10 or more years. By contrast, AD risk was not reduced among those who had initiated HT 5 or more years after menopause. Instead, rates were increased among those who began “opposed” estrogen-progestin compounds within the 3 years preceding the Cache County Study baseline (adjusted hazard ratio 1.93; 95% confidence interval 0.94–3.96). This last hazard ratio was similar to the ratio of 2.05 reported in randomized trial participants assigned to opposed HT.
Association of HT use and risk of AD may depend on timing of use. Although possibly beneficial if taken during a critical window near menopause, HT (especially opposed compounds) initiated in later life may be associated with increased risk. The relation of AD risk to timing and type of HT deserves further study.
PMCID: PMC3525314  PMID: 23100399
8.  Secular changes in at-risk drinking in Sweden: birth cohort comparisons in 75-year-old men and women 1976–2006 
Age and Ageing  2013;43(2):228-234.
Background: little is known about the prevalence of at-risk drinking in older adults.
Objective: to compare rates of at-risk drinking in 75-year-olds examined in 1976–77 and in 2005–06.
Design: cross-sectional survey.
Setting: two samples representative of the general population in Gothenburg, Sweden.
Participants: 75-year-olds born in 1901–02 (n = 303) and in 1930 (n = 753).
Methods: participants took part in a multidisciplinary study on health and ageing. Protocols regarding alcohol consumption were identical for both cohorts. Total weekly alcohol intake was estimated and at-risk drinking was defined as ≥100 g alcohol/week.
Results: the proportion abstaining differed significantly between birth cohorts (18% in 1976–77 versus 9% in 2005, P < 0.001). Frequencies of drinking beer and liquor were similar in the two cohorts for men, but were lower for women in the later-born cohort. Proportions drinking wine were higher in the later-born cohort for both sexes. Total weekly alcohol intake was higher for both men and women. At-risk drinking was observed in 19.3% of the men in the earlier-born cohort, and in 27.4% in the later-born cohort (P = 0.117). Corresponding figures for women were 0.6 and 10.4% (P < 0.001). At-risk drinking was significantly associated with birth cohort in women (OR: 13.77, CI: 1.82–104.0, P = 0.011) and the occupational group in men (OR: 1.60, CI: 1.13–2.26, P = 0.008).
Conclusions: alcohol consumption in 75-year-olds has changed markedly, especially in women. Studies need to be carried out in varied settings in order to evaluate the clinical and public health implications of changing trends in alcohol consumption.
PMCID: PMC3927771  PMID: 24067499
older people; alcohol; at-risk drinking; cohort comparisons
9.  Common psychosocial stressors in middle-aged women related to longstanding distress and increased risk of Alzheimer's disease: a 38-year longitudinal population study 
BMJ Open  2013;3(9):e003142.
To study the relation among psychosocial stressors, long-standing distress and incidence of dementia, in a sample of women followed from midlife to late life.
Prospective longitudinal population study.
The analyses originate from the prospective population study of women in Gothenburg, Sweden, a representative sample of women examined in 1968 (participation rate 90%) and re-examined in 1974, 1980, 1992, 2000 and 2005.
800 women born in 1914, 1918, 1922 and 1930 who were systematically selected for a psychiatric examination at baseline, in 1968.
Primary and secondary outcome measures
18 psychosocial stressors (eg, divorce, widowhood, work problems and illness in relative) were obtained at baseline. Symptoms of distress were measured according to a standardised question at each study wave. Dementia was diagnosed according to Diagnostic and Statistical Manual of Mental Disorders (DSM-III-R) criteria based on information from neuropsychiatric examinations, informant interviews, hospital records, and registry data, and measured through the whole study period.
During the 37 years of follow-up, 153 women developed dementia (104 of those had Alzheimer's disease (AD)). Number of psychosocial stressors in 1968 was associated (HR, 95% CI) with higher incidence of dementia (1.15, 1.04 to 1.27) and AD (1.20, 1.07 to 1.35) between 1968 and 2005, in multivariate Cox regressions. Number of psychosocial stressors in 1968 was also associated (OR, 95% CI) with distress in 1968 (1.48, 1.32 to 1.67), 1974 (1.31, 1.17 to 1.46), 1980 (1.27, 1.11 to 1.45), 2000 (1.39, 1.14 to 1.70) and 2005 (1.35, 1.02 to 1.79), in multivariate logistic regressions. Number of psychosocial stressors (HR 1.17, 95% CI 1.03 to 1.33) and long-standing distress (1968–1974–1980) (HR 1.58, 95% CI 1.03 to 2.45) were independently associated with AD.
Our study shows that common psychosocial stressors may have severe and long-standing physiological and psychological consequences. However, more studies are needed to confirm these results and investigate whether more interventions such as stress management and behavioural therapy should be initiated in individuals who have experienced psychosocial stressors.
PMCID: PMC3787482  PMID: 24080094
10.  Depression, Prevalence and Some Risk Factors in Elderly Nursing Homes in Tehran, Iran 
Iranian Journal of Public Health  2013;42(6):559-569.
The most common geriatric psychiatric disorder is depression, known to be a multi factorial disorder. However, the influence of common preventable factors is yet to be discovered. This study was designed to evaluate the prevalence of depression and some possible risk factors in elderly residents of nursing homes in Iran.
Data on demographic characteristics, nutritional and health status of 244 residents aged 60 years or older were collected from seventeen nursing homes in Tehran, Iran, during 2010 to 2012. Depression was assessed and classified according to the 15-item GDS. Univariate and then multivariate complex sample survey ordinal regression analysis was performed to investigate the association between depression and the risk factors.
The average age of the 244 cases studied was 75.8 (±8.7) years, 53.3% were female (of whom 74.2% were housewives), 43.4% illiterate, and 32.0% were divorced or were living separately. The percentages of non-depressed, mild, moderate and severe depression were 9.8%, 50.0%, 29.5% and 10.7%, respectively. Multivariate analysis showed that dissatisfaction with personnel of nursing homes and food quality had odds ratios of 2.91 (1.33–6.36) and 2.64 (1.44–4.87), corresponding to greater odds of having a higher grade depression. Moreover, those who rested or walked had significantly higher risk of a more severe depression in comparison with those who did not (OR of 2.25 (1.50–3.38) and 1.98 (1.24–3.18), respectively), however, studying had a protective odds ratio of 0.17 (0.13–0.22).
Depression was very common in our sample and their lifestyle influenced its prevalence.
PMCID: PMC3744252  PMID: 23967423
Depression; Elderly; Nursing homes; Iran
11.  Nonlinear Blood Pressure Effects on Cognition in Old Age: Separating Between-Person and Within-Person Associations 
Psychology and aging  2011;27(2):375-383.
Midlife hypertension is associated with increased risk of cognitive impairment in later life. The association between blood pressure (BP) in older ages and cognition is less clear. In this study we provide estimates of between-person and within-person associations of BP and cognition in a population-based sample (N = 382) followed from age 70 across 12 occasions over 30 years. Between-person associations refer to how individual differences in BP relates to individual differences in cognition. Within-person associations refer to how individual and time specific changes in BP relate to variation in cognition. Hierarchical linear models were fitted to data from three cognitive measurements (verbal ability, spatial ability, and perceptual speed) while accounting for demographic and health-related covariates. We found consistent nonlinear between-person associations between diastolic BP (DBP) and cognition, such that both low (<75 mmHg) and high (>95 mmHg) pressure were associated with poorer cognition. Within-person decreases in systolic BP (SBP) and DBP were associated with decreases in perceptual speed. Notably, between-person and within-person estimates did not reveal similar associations, suggesting the need to separate the two effects in the analysis of associations between BP and cognition in old age.
PMCID: PMC3625422  PMID: 21988152
blood pressure; cognitive function; longitudinal study; between-person; within-person associations
12.  Suicidal feelings in the twilight of life: a cross-sectional population-based study of 97-year-olds 
BMJ Open  2013;3(2):e002260.
To examine the occurrence of past month suicidal feelings in extreme old age. Further, to identify factors associated with such feelings.
Cross-sectional population-based study.
Gothenburg, Sweden.
269 adults (197 women, 72 men) without dementia born in 1901–1909 who participated in a psychiatric examination.
Main outcome measures
Death thoughts and suicidal feelings. The latter were rated in accordance with the Paykel questions (life not worth living, death wishes, thoughts of taking own life, seriously considered taking own life, attempted suicide) during the past month.
One quarter of the sample (26.7%) reported that they thought about their own death at least once a month. Past month thoughts that life was not worth living were acknowledged by 7.9% of the total sample, death wishes by 10.5% and thoughts of taking life by 3.8%. Few had serious thoughts of taking own life (0.8%) and none had attempted suicide. In all, 11.5% acknowledged some level of suicidal feelings. Most (77.4%) of those who reported such feelings fulfilled criteria for neither major nor minor depression. Neither poor perceived health nor disability (hearing, vision and motor function) was associated with suicidal feelings. Problematic sleep and deficient social contacts were also related to suicidal feelings after adjustment for depression.
Suicidal feelings may occur outside the context of depression and disability in this age group. Results can inform clinicians who care for persons who reach extreme old age.
PMCID: PMC3586106  PMID: 23377994
Cross Sectional Study; Depression
13.  Does low-dose acetylsalicylic acid prevent cognitive decline in women with high cardiovascular risk? A 5-year follow-up of a non-demented population-based cohort of Swedish elderly women 
BMJ Open  2012;2(5):e001288.
The aim of this study was to examine whether low-dose acetylsalicylic acid (ASA) influences the rate of cognitive change in elderly women.
Prospective, population-based cohort study.
The city of Gothenburg, Sweden, including those living in private households as well as in residential care.
The sample was derived from the Prospective Population Study of Women and from the H70 Birth Cohort Study in Gothenburg, Sweden. Both samples were obtained from the Swedish Population Register, based on birth date, and included 789 (response rate 71%) women aged 70–92 years. After the exclusion of individuals with dementia and users of warfarin, clopidogrel or heparin at baseline, 681 women were examined. Among all participants, 95.4% (N=601) had a high cardiovascular risk (CVD), defined as 10% or higher 10-year risk of any CVD event according to the Framingham heart study and 129 used low-dose ASA (75–160 mg daily) at baseline. After 5 years a follow-up was completed by 489 women.
Primary outcome and secondary outcome measures
Cognitive decline and dementia incidence in relation to the use of low-dose ASA and cardiovascular risk factors. Cognition was measured using the Mini Mental State Examination (MMSE), word fluency, naming ability and memory word tests. Dementia was diagnosed according to the DSM-III-R criterion. As secondary outcome incidence of stroke and peptic ulcer in relation to low-dose ASA use was studied.
Women on regular low-dose ASA declined less on MMSE at follow-up than those not on ASA. This difference was even more pronounced in those who had ASA at both examinations (p=0.004 compared with never users; n=66 vs n=338). All other cognitive tests showed the same trends. There were no differences between the groups regarding short-term risk for dementia (N=41).
Low-dose ASA treatment may have a neuroprotective effect in elderly women at high cardiovascular risk.
PMCID: PMC3488756  PMID: 23035037
14.  Early Parental Death and Remarriage of Widowed Parents as Risk Factors for Alzheimer’s Disease. The Cache County Study 
Early parental death is associated with lifelong tendencies toward depression and chronic stress. We tested the hypothesis that, early parental death is associated with higher risk for Alzheimer’s disease (AD) in offspring.
A population-based epidemiological study of dementia with detailed clinical evaluations, linked to one of the world’s richest sources of objective genealogical and vital statistics data.
Home visits with residents of a rural county in northern Utah.
4,108 subjects, aged 65-105.
Multi-stage dementia ascertainment protocol implemented in four triennial waves, yielding expert consensus diagnoses of 570 participants with AD and 3,538 without dementia. Parental death dates, socioeconomic status and parental remarriage after widowhood were obtained from the Utah Population Database, a large genealogical database linked to statewide birth and death records.
Mother’s death during subject’s adolescence was significantly associated with higher rate of AD in regression models that included age, gender, education, APOE genotype, and socioeconomic status. Father’s death before subject age 5 showed a weaker association. In stratified analyses, associations were significant only when the widowed parent did not remarry. Parental death associations were not moderated by gender or APOE genotype. Findings were specific to AD and not found for non-AD dementia.
Parental death during childhood is associated with higher prevalence of AD, with different critical periods for father’s vs. mother’s death, with strength of these associations attenuated by remarriage of the widowed parent.
PMCID: PMC3164808  PMID: 21873837
15.  Temporal Lobe Atrophy and White Matter Lesions are Related to Major Depression over 5 years in the Elderly 
Neuropsychopharmacology  2010;35(13):2638-2645.
The influence of organic brain changes on the development of depression in the elderly is uncertain. Cross-sectional studies, most often from clinical samples, report associations with brain atrophy and cerebrovascular disease, while longitudinal population studies have given mixed results. Our aim was to investigate whether cortical atrophy and white matter lesions (WMLs) on computed tomography (CT) predict occurrence of depression in the elderly. This is a prospective population-based study with 5-year follow-up. The baseline sample included 525 elderly subjects, aged 70–86 years, without dementia or major depression, with a score on the Mini-Mental State Examination above 25, and without dementia at follow-up. Cortical atrophy and WMLs were evaluated at baseline using CT. The main outcome measure was development of major or minor depression at follow-up according to Diagnostic and Statistical Manual of Mental Disorders, fourth edition, as evaluated using neuropsychiatric examinations and hospital discharge registers. Logistic regression was used to estimate risk. Over the period of 5 years, 20 individuals developed major and 63 minor depression. Presence of temporal lobe atrophy (odds ratio (OR)=2.81, 95% confidence interval (CI) 1.04–7.62) and moderate-to-severe WMLs (OR=3.21, 95% CI 1.00–10.26) independently predicted major, but not minor, depression after controlling for various confounders. Other brain changes did not predict occurrence of depression. Our findings suggest that temporal lobe atrophy and WMLs represent relatively independent and complementary pathways to major depression in the elderly. This may have implications for prevention, as both neurodegeneration and cerebrovascular disease have been related to preventable factors.
PMCID: PMC3055580  PMID: 20881949
depression; elderly; brain atrophy; white matter lesions; population; longitudinal; aging/geriatrics; imaging, clinical or preclinical; epidemiology; depression, unipolar/bipolar; brain atrophy; longitudinal; white matter lesions; depression; population
16.  Increased Risk of Dementia When Spouse Has Dementia? The Cache County Study 
Chronic psychosocial stress in caregivers can lead to adverse health outcomes including depression, anxiety, and cognitive decline. We examined the effects of having a spouse with dementia on one’s own risk for incident dementia.
Population-based study of incident dementia in spouses of persons with dementia.
Rural county in northern Utah.
2,442 subjects (1,221 married couples) aged 65 and older.
Incident dementia was diagnosed in 255 subjects, with onset defined as age when subject met DSM-III-R criteria for dementia. Cox proportional hazards regression tested the effect of time-dependent exposure to dementia in one’s spouse, adjusted for potential confounders.
A subject whose spouse experienced incident dementia onset had a six-fold increase in the hazard for incident dementia compared to subjects whose spouses were dementia free [Hazard Rate Ratio (HRR)=6.0, 95% CI: 2.2–16.2 (p<.001)]. In sex-specific analyses, husbands had higher risks (HRR=11.9, 95% CI: 1.7–85.5, p=.014) compared to wives (HRR=3.7, 95% CI: 1.2–11.6, p=.028).
The chronic and often severe stress associated with dementia caregiving may exert substantial risk for the development of dementia in spouse caregivers. Additional (not mutually exclusive) explanations for findings are discussed.
PMCID: PMC2945313  PMID: 20722820
dementia; caregiving; stress
17.  Association of the RAGE G82S polymorphism with Alzheimer’s disease 
Journal of Neural Transmission  2010;117(7):861-867.
The receptor for advanced glycation end-products (RAGE) has been implicated in several pathophysiological processes relevant to Alzheimer’s disease (AD), including transport and synaptotoxicity of AD-associated amyloid β (Aβ) peptides. A recent Chinese study (Li et al. in J Neural Transm 117:97–104, 2010) suggested an association between the 82S allele of the functional single nucleotide polymorphism (SNP) G82S (rs2070600) in the RAGE-encoding gene AGER and risk of AD. The present study aimed to investigate associations between AGER, AD diagnosis, cognitive scores and cerebrospinal fluid AD biomarkers in a European cohort of 316 neurochemically verified AD cases and 579 controls. Aside from G82S, three additional tag SNPs were analyzed to cover the common genetic variation in AGER. The 82S allele was associated with increased risk of AD (Pc = 0.04, OR = 2.0, 95% CI 1.2–3.4). There was no genetic interaction between AGER 82S and APOE ε4 in producing increased risk of AD (P = 0.4), and none of the AGER SNPs showed association with Aβ42, T-tau, P-tau181 or mini-mental state examination scores. The data speak for a weak, but significant effect of AGER on risk of AD.
PMCID: PMC2895876  PMID: 20567859
Alzheimer’s disease; RAGE; AGER; Advanced glycosylation end product-specific receptor; SNP; Haplotype
18.  Cerebrospinal fluid β‐amyloid 1–42 concentration may predict cognitive decline in older women 
Low levels of cerebrospinal fluid (CSF) β‐amyloid 1–42 (Aβ42) and high total tau (T‐tau) are diagnostic for manifest Alzheimer's disease. It is not known, however, whether these biomarkers may be risk indicators for cognitive decline in otherwise healthy older people.
The longitudinal relationship between CSF markers, Aβ42 and T‐tau, measured in 1992, and change in Mini‐Mental State Examination (ΔMMSE) score between 1992 and 2002 were investigated in 55 women (aged 70–84 years, mean (SD) MMSE score = 28.3 (1.5)), who were participants in the Prospective Population Study of Women in Gothenburg, Sweden. These women did not have dementia when they experienced lumbar puncture in 1992–3.
Over the 8‐year follow‐up period, ΔMMSE (range =  +3 to −21 points) was correlated with Aβ42 (Spearman's r = 0.40, p = 0.002), such that lower levels of Aβ42 were related to greater decline. This was also observed after excluding 4 women who developed dementia between 1992 and 2002 (Spearman's r = 0.34, p = 0.019). A multivariate logistic regression model predicting a decline of ⩾5 points on the MMSE (observed in six women), or a risk of developing dementia over the 8‐year follow‐up period (observed in four women), including age, education, Aβ42 and T‐tau as covariates, showed that Aβ42 was the sole predictor of significant cognitive decline or dementia (OR per 100 pg/ml Aβ42 = 2.24, 95% CI 1.19 to 4.22, p = 0.013).
Low levels of CSF Aβ42 may predict cognitive decline among older women without dementia.
PMCID: PMC2117838  PMID: 17098843
19.  The inclusion of cognition in vascular risk factor clinical practice guidelines 
People with vascular risk factors are at increased risk for cognitive impairment as well as vascular disease. The objective of this study was to evaluate whether vascular risk factor clinical practice guidelines consider cognition as an outcome or in connection with treatment compliance.
Articles from PubMed, EMBASE, and the Cochrane Library were assessed by at least two reviewers and were included if: (1) Either hypertension, high cholesterol, diabetes, or atrial fibrillation was targeted; (2) The guideline was directed at physicians; (3) Adult patients (aged 19 years or older) were targeted; and (4) The guideline was published in English. Of 91 guidelines, most were excluded because they were duplicates, older versions, or focused on single outcomes.
Of the 20 clinical practice guidelines that met inclusion criteria, five mentioned cognition. Of these five, four described potential treatment benefits but only two mentioned that cognition may affect compliance. No guidelines adequately described how to screen for cognitive impairment.
Despite evidence that links cognitive impairment to vascular risk factors, only a minority of clinical practice guidelines for the treatment of vascular risk factors consider cognition as either an adverse outcome or as a factor to consider in treatment.
PMCID: PMC2785866  PMID: 19966911
clinical practice guidelines; evidence-based medicine; vascular risk; cognition; target organ damage
20.  Church Attendance and New Episodes of Major Depression in a Community Study of Older Adults: The Cache County Study 
We examined the relation between church attendance, membership in the Church of Jesus Christ of Latter-Day Saints (LDS), and major depressive episode, in a population-based study of aging and dementia in Cache County, Utah. Participants included 2,989 nondemented individuals aged between 65 and 100 years who were interviewed initially in 1995 to 1996 and again in 1998 to 1999. LDS church members reported twice the rate of major depression that non-LDS members did (odds ratio = 2.56, 95% confidence interval = 1.07-6.08). Individuals attending church weekly or more often had a significantly lower risk for major depression. After controlling for demographic and health variables and the strongest predictor of future episodes of depression, a prior depression history, we found that church attendance more often than weekly remained a significant protectant (odds ratio = 0.51, 95% confidence interval = 0.28-0.92). Results suggest that there may be a threshold of church attendance that is necessary for a person to garner long-term protection from depression. We discuss sociological factors relevant to LDS culture.
PMCID: PMC2673327  PMID: 18559677
Church Attendance; Depression; Latter Day Saints
21.  Secular trends in self reported sexual activity and satisfaction in Swedish 70 year olds: cross sectional survey of four populations, 1971-2001 
BMJ : British Medical Journal  2008;337(7662):151-154.
Objective To study secular trends in self reported sexual behaviour among 70 year olds.
Design Cross sectional survey.
Settings Four samples representative of the general population in Gothenburg, Sweden.
Participants 1506 adults (946 women, 560 men) examined in 1971-2, 1976-7, 1992-3, and 2000-1.
Main outcome measures Sexual intercourse, attitudes to sexuality in later life, sexual dysfunctions, and marital satisfaction.
Results From 1971 to 2000 the proportion of 70 year olds reporting sexual intercourse increased among all groups: married men from 52% to 68% (P=0.002), married women from 38% to 56% (P=0.001), unmarried men from 30% to 54% (P=0.016), and unmarried women from 0.8% to 12% (P<0.001). Men and women from later birth cohorts reported higher satisfaction with sexuality, fewer sexual dysfunctions, and more positive attitudes to sexuality in later life than those from earlier birth cohorts. A larger proportion of men (57% v 40%, P<0.001) and women (52% v 35%, P<0.001) reported very happy relationships in 2000-1 compared with those in 1971-2. Sexual debut before age 20 increased in both sexes: in men from 52% to 77% (P<0.001) and in women from 19% to 64% (P<0.001).
Conclusion Self reported quantity and quality of sexual experiences among Swedish 70 year olds has improved over a 30 year period.
PMCID: PMC2483873  PMID: 18614505
22.  Secular trends in self reported sexual activity and satisfaction in Swedish 70 year olds: cross sectional survey of four populations, 1971-2001 
Objective To study secular trends in self reported sexual behaviour among 70 year olds.
Design Cross sectional survey.
Settings Four samples representative of the general population in Gothenburg, Sweden.
Participants 1506 adults (946 women, 560 men) examined in 1971-2, 1976-7, 1992-3, and 2000-1.
Main outcome measures Sexual intercourse, attitudes to sexuality in later life, sexual dysfunctions, and marital satisfaction.
Results From 1971 to 2000 the proportion of 70 year olds reporting sexual intercourse increased among all groups: married men from 52% to 68% (P=0.002), married women from 38% to 56% (P=0.001), unmarried men from 30% to 54% (P=0.016), and unmarried women from 0.8% to 12% (P<0.001). Men and women from later birth cohorts reported higher satisfaction with sexuality, fewer sexual dysfunctions, and more positive attitudes to sexuality in later life than those from earlier birth cohorts. A larger proportion of men (57% v 40%, P<0.001) and women (52% v 35%, P<0.001) reported very happy relationships in 2000-1 compared with those in 1971-2. Sexual debut before age 20 increased in both sexes: in men from 52% to 77% (P<0.001) and in women from 19% to 64% (P<0.001).
Conclusion Self reported quantity and quality of sexual experiences among Swedish 70 year olds has improved over a 30 year period.
PMCID: PMC2483873  PMID: 18614505
23.  A Lone Walk 
BMJ : British Medical Journal  2001;322(7301):1550.
PMCID: PMC1120592
24.  Age-related differences in recommended anthropometric cut-off point validity to identify cardiovascular risk factors in ostensibly healthy women 
Aim: To investigate validity of widely recommended anthropometric and total fat percentage cut-off points in screening for cardiovascular risk factors in women of different ages. Methods: A population-based sample of 1002 Swedish women aged 38, 50, 75 (younger, middle-aged and elderly, respectively) underwent anthropometry, health examinations and blood tests. Total fat was estimated (bioimpedance) in 670 women. Sensitivity, specificity of body mass index (BMI; ≥25 and ≥30), waist circumference (WC; ≥80 cm and ≥88 cm) and total fat percentage (TF; ≥35%) cut-off points for cardiovascular risk factors (dyslipidaemias, hypertension and hyperglycaemia) were calculated for each age. Cut-off points yielding high sensitivity together with modest specificity were considered valid. Women reporting hospital admission for cardiovascular disease were excluded. Results: The sensitivity of WC ≥80 cm for one or more risk factors was ~60% in younger and middle-aged women, and 80% in elderly women. The specificity of WC ≥80 cm for one or more risk factors was 69%, 57% and 40% at the three ages (p < .05 for age trends). WC ≥80 cm yielded ~80% sensitivity for two or more risk factors across all ages. However, specificity decreased with increasing age (p < .0001), being 33% in elderly. WC ≥88 cm provided better specificity in elderly women. BMI and TF % cut-off points were not better than WC. Conclusions: Validity of recommended anthropometric cut-off points in screening asymptomatic women varies with age. In younger and middle-age, WC ≥80 cm yielded high sensitivity and modest specificity for two or more risk factors, however, sensitivity for one or more risk factor was less than optimal. WC ≥88 cm showed better validity than WC ≥80 cm in elderly. Our results support age-specific screening cut-off points for women.
PMCID: PMC4257998  PMID: 25294689
Anthropometric cut-off points; waist circumference; total fat %; cardiovascular risk factors; hypertension; dyslipidaemia; screening; public health; sensitivity; specificity

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