Social Health and Cognitive Change in Old Age: Role of Brain Reserve.

OBJECTIVE: Individual aspects of social health (SH; eg, network, engagement, support) have been linked to cognitive health. However, their combined effect and the role of the structural properties of the brain (brain reserve [BR]) remain unclear. We investigated the interplay of SH and BR on cognitive change in older adults. METHODS: Within the Swedish National Study on Aging and Care-Kungsholmen, 368 dementia-free adults aged ≥60 years with baseline brain magnetic resonance imaging were followed over 12 years to assess cognitive change. A measure of global cognition was computed at each of the 5 waves of assessment by averaging domain-specific Z scores for episodic memory, perceptual speed, semantic memory, and letter and category fluency. An SH composite score was computed at baseline by combining leisure activities and social network. BR was proxied by total brain tissue volume (TBTV). Linear mixed models (adjusted for sociodemographic, vascular, and genetic factors) were used to estimate cognitive trajectories in relation to SH and TBTV. Interaction analysis and stratification were used to examine the interplay between SH and TBTV. RESULTS: Moderate-good SH (n = 245; vs poor, ß-slope = 0.01, 95% confidence interval [CI] = 0.002-0.02, p = 0.018) and moderate-to-large TBTV (n = 245; vs small, ß-slope = 0.03, 95% CI = 0.02-0.04, p < 0.001) were separately associated with slower cognitive decline. In stratified analysis, moderate-good SH was associated with higher cognitive levels (but not change) only in participants with moderate-to-large TBTV (ß-intercept = 0.21, 95% CI = 0.06-0.37, p < 0.01; interaction SH * TBTV, p < 0.05). INTERPRETATION: Our findings highlight the interplay between SH and BR that likely unfolds throughout the entire life course to shape old-age cognitive outcomes. ANN NEUROL 2023;93:844-855.

Interactive association between insomnia symptoms and sleep duration for the risk of dementia-a prospective study in the Swedish National March Cohort.

OBJECTIVE: Given the importance of sleep in maintaining neurocognitive health, both sleep duration and quality might be component causes of dementia. However, the possible role of insomnia symptoms as risk factors for dementia remain uncertain. METHODS: We prospectively studied 22,078 participants in the Swedish National March Cohort who were free from dementia and stroke at baseline. Occurrence of dementia was documented by national registers during a median follow-up period of 19.2 years. Insomnia symptoms and sleep duration were ascertained by Karolinska Sleep Questionnaire. Multivariable Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: Compared to participants without insomnia at baseline, those who reported any insomnia symptom experienced a greater incidence of dementia during follow-up (HR 1.08, 95% CI: 1.03, 1.35). Difficulty initiating sleep versus non-insomnia (HR 1.24, 95% CI: 1.02, 1.52), but not difficulty maintaining sleep or early morning awakening was associated with an increased risk of dementia. Short sleep duration was associated with increased risk of dementia (6 h vs. 8 h, HR 1.29, 95% CI: 1.11-1.51; 5 h vs. 8 h, HR 1.26, 95% CI: 1.00-1.57). Stratified analyses suggested that insomnia symptoms increased the risk of dementia only amongst participants with ≥7 h sleep (vs. non-insomnia HR 1.24, 95% CI: 1.00-1.54, P = 0.05), but not amongst short sleepers (<7 h). Short sleep duration also did not further inflate the risk of dementia amongst insomniacs. CONCLUSION: Insomnia and short sleep duration increase the risk of dementia amongst middle-aged to older adults.

Shared risk and protective factors between Alzheimer's disease and ischemic stroke: A population-based longitudinal study.

INTRODUCTION: Stroke, especially ischemic stroke's (IS) link with Alzheimer's disease (AD) remains unclear. METHODS: This prospective cohort study included 2459 AD- and cerebrovascular disease-free older adults at baseline (mean age 71.9 ± 10.3 years, Stockholm, Sweden). Using Cox regressions, shared risk factors (SRFs) and shared protective factors (SPFs) between AD and IS were recognized when their hazard ratios in both AD and IS models were significant and in the same direction. RESULTS: During the follow-up period of up to 15 years, 132 AD and 260 IS mutually exclusive cases were identified. SRFs were low education, sedentary lifestyle, and heart diseases. High levels of psychological well-being, actively engaging in leisure activities, and a rich social network were SPFs. Having ≥1 SPF reduced 47% of AD and 28% of IS risk among people with a low risk profile (<2 SRFs), and 38% of AD and 31% of IS risk with a high risk profile (≥2 SRFs). In total, 57.8% of AD/IS cases could be prevented if individuals have ≥1 SPF and no SRF. DISCUSSION: AD and IS share risk/protective profiles, and SPFs seem to counteract the adverse effects of SRFs on both AD and IS.

Sex differences in dementia and response to a lifestyle intervention: Evidence from Nordic population-based studies and a prevention trial.

INTRODUCTION: Evidence on sex differences in the risk for dementia has been mixed. The goal was to assess sex differences in the development of dementia, and in the effects of a lifestyle intervention. METHODS: Two strategies were adopted, one using combined data from three large Nordic population-based cohort studies (n = 2289), adopting dementia as outcome, and 2-year multidomain lifestyle intervention (n = 1260), adopting cognitive change as outcome. RESULTS: There was higher risk for dementia after age 80 years in women. The positive effects of the lifestyle intervention on cognition did not significantly differ between men and women. Sex-specific analyses suggested that different vascular, lifestyle, and psychosocial risk factors are important for women and men in mid- and late-life. CONCLUSION: Women had higher risk for dementia among the oldest individuals. Lifestyle interventions may be effectively implemented among older men and women.

Genetic risk of dementia mitigated by cognitive reserve: A cohort study.

OBJECTIVE: We investigated whether cognitive reserve modifies the risk of dementia attributable to apolipoprotein ε4 (APOE-ε4), a well-known genetic risk factor for dementia. METHODS: We followed 2,556 cognitively intact participants aged ≥60 years from the ongoing prospective community-based Swedish National Study on Aging and Care in Kungsholmen (SNAC-K). Dementia was ascertained through clinical and neuropsychological assessments and diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, 4th edition criteria. Structural equation modeling was used to generate a cognitive reserve indicator from 4 previously validated contributors: early life education, midlife substantive work complexity, late life leisure activities, and late life social networks. Cox proportional hazard models estimated dementia risk in relation to cognitive reserve indicator. The interaction between the cognitive reserve indicator and APOE-ε4 was assessed on multiplicative and additive scales. RESULTS: After an average of 6.3 years (range = 2.1-10.7) of follow-up, 232 dementia cases were ascertained. Relative to individuals in the lowest tertile of cognitive reserve indicator, those with moderate and high reserve were at a reduced risk of dementia. There was no multiplicative interaction between APOE-ε4 status and cognitive reserve indicator (p = 0.113). Additive interaction was statistically significant. Relative to APOE-ε4 carriers with low cognitive reserve, ε4 carriers with high reserve had a reduced risk of dementia (hazard ratio [HR] = 0.28, 95% confidence interval [CI] = 0.13-0.59). The magnitude of risk reduction was similar in ε4 noncarriers with a high cognitive reserve indicator (HR = 0.24, 95% CI = 0.15-0.40). INTERPRETATION: Lifelong engagement in reserve-enhancing activities attenuates the risk of dementia attributable to APOE-ε4. Promoting cognitive reserve might be especially effective in subpopulations with high genetic risk of dementia. ANN NEUROL 2019.

Low Mood and Risk of Dementia: The Role of Marital Status and Living Situation.

OBJECTIVE: This study aims to explore whether low mood is related to an increased dementia risk in two cohorts of older adults of different generations, and whether marital status and living situation modify this association. METHODS: Participants (≥70 years), free from dementia and living at home, were identified from two population-based studies: the Kungsholmen Project (KP; n = 1,197) and the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K; n = 1,402). Low mood was obtained by self-report (KP and SNAC-K) at baseline in 1987-89 (KP) and 2001-04 (SNAC-K). Incident dementia cases were ascertained over 9 years, using the same diagnostic procedures and comparable criteria for the two cohorts (DSM-III-R in KP and DSM-IV-TR in SNAC-K). Hazard ratios (HR) were derived from Cox proportional hazards models. RESULTS: Those having low mood at baseline were at higher risk of dementia in both cohorts combined (HR: 1.2, 95% confidence interval (CI): 1.0-1.4) than those without low mood. However, an increased risk was detected only in those who did not have a partner (HR: 1.5, 95% CI: 1.2-1.9), or lived alone (HR: 1.5, 95% CI: 1.2-1.9), but not among those who had a partner or lived with someone (HR: 0.8, 95% CI: 0.5-1.2). CONCLUSION: Marital status and living situation have the potential to buffer the detrimental effects of low mood on dementia onset. Thus, specific attention from health care should target individuals having low mood and who do not have a partner or live alone.

Association of diabetes with stroke and post-stroke dementia: A population-based cohort study.

INTRODUCTION: The impact of prediabetes and diabetes on stroke and the development of dementia after a stroke remain unclear. METHODS: A total of 2655 dementia-free participants (including a stroke-free cohort and a prevalent stroke cohort) were followed-up for 12 years. Dementia and post-stroke dementia were determined by clinical examinations and national registry data. Diabetes was ascertained via medical examination, medication use, medical records, or glycated hemoglobin (HbA1c) ≥6.5%. Prediabetes was defined as HbA1c ≥5.7% in diabetes-free participants. RESULTS: In the stroke-free cohort, 236 participants developed ischemic stroke, and 47 developed post-stroke dementia. Diabetes was associated with ischemic stroke (hazard ratio [HR] 1.76, 95% confidence interval [CI] 1.16 to 2.67) and post-stroke dementia (HR 2.56, 95% CI 1.04 to 6.25). In the prevalent stroke cohort, diabetes was also related to dementia risk. Prediabetes was not significantly related to stroke or post-stroke dementia. DISCUSSION: Diabetes, but not prediabetes, is associated with an increased risk of ischemic stroke and post-stroke dementia.

Mid- to late-life migraine diagnoses and risk of dementia: a national register-based follow-up study.

BACKGROUND: Previous studies found an association between migraine and dementia, which are two leading causes of disability. However, these studies did not differentiate between migraine types and did not investigate all prevalent dementia subtypes. The main objective of this national register-based study was to investigate whether migraine was a risk factor for dementia. Additionally, we explored potential differences in dementia risk for migraine with and without aura. METHODS: We obtained data on birth cohorts born between 1935 and 1956 (n = 1,657,890) from Danish national registers. Individuals registered with migraine before age 59 (n = 18,135) were matched (1:5) on sex and birthdate with individuals without migraine (n = 1,378,346). Migraine was defined by International Classification of Diseases (ICD) diagnoses and dementia was defined by ICD diagnoses and anti-dementia medication. After matching, 62,578 individuals were eligible for analysis. For the statistical analyses, we used Cox regression models and adjusted for socio-demographic factors and several psychiatric and somatic morbidities. RESULTS: During a median follow-up time of 6.9 (IQR: 3.6-11.2) years, 207 individuals with migraine developed dementia. Compared with individuals without migraine, we found a 50% higher rate of dementia among individuals with migraine (HR = 1.50; 95% CI: 1.28-1.76). Individuals without aura had a 19% higher rate of dementia (HR = 1.19; 95% CI: 0.84-1.70), and individuals with aura had a two times higher rate of dementia (HR = 2.11; 95% CI: 1.48-3.00). CONCLUSIONS: Our findings support the hypothesis that migraine is a midlife risk factor for dementia in later life. The higher rate of dementia in individuals with a hospital-based diagnosis of migraine with aura emphasizes the need for studies on pathological mechanisms and potential preventative measures. Furthermore, given that only hospital-based migraine diagnoses were included in this study, future research should also investigate migraine cases derived from the primary healthcare system to include less severe migraine cases.

Psychosocial working conditions, trajectories of disability, and the mediating role of cognitive decline and chronic diseases: A population-based cohort study.

BACKGROUND: Unfavorable psychosocial working conditions have been associated with cognitive decline and chronic diseases, both of which may subsequently accelerate functional dependence. This study aimed to investigate the association between job demand-control-support combinations and trajectories of disability in later life and to further explore the role of cognitive decline and the co-occurrence of chronic diseases in mediating this association. METHODS AND FINDINGS: In this cohort study, 2,937 community dwellers aged 60+ years (mean age 73 ± 10.6; 62.9% female) residing in the Kungsholmen District of Stockholm, Sweden, participated in the baseline survey (2001-2004) and were followed up to 12 years. Lifelong occupational history was obtained through a standardized interview; job demands, job control, and social support at work in the longest-held occupation were graded with a psychosocial job-exposure matrix. Job control, demands, and social support were dichotomized using the median values from the matrix, respectively, to further generate demand-control-support combinations. Disability was measured by summing the number of impaired basic and instrumental activities of daily living. Global cognitive function was assessed by Mini-Mental State Examination. Chronic conditions were ascertained by clinical examinations, medical history, and patient clinical records; the total number of chronic diseases was summed. Data were analyzed using linear mixed-effects models and mediation analysis. Age, sex, education, alcohol consumption, smoking, leisure activity engagement, early-life socioeconomic status, occupational characteristic and physical demands, and baseline cognitive function and number of chronic diseases were adjusted for in the analyses. Compared with active jobs (high control/high demands; n = 1,807), high strain (low control/high demands; n = 328), low strain (high control/low demands; n = 495), and passive jobs (low control/low demands; n = 307) were all associated with a faster rate of disability progression (ß = 0.07, 95% CI 0.02-0.13, p = 0.01; ß = 0.10, 95% CI 0.06-0.15, p < 0.001; ß = 0.11, 95% CI 0.05-0.18, p < 0.001). The association between high strain and disability progression was only shown in people with low social support at work (ß = 0.13, 95% CI 0.07-0.19, p < 0.001), but not in those with high social support (ß = 0.004, 95% CI -0.09 to 0.10, p = 0.93). Moreover, we estimated that the association between demand-control status and disability trajectories was mediated 38.5% by cognitive decline and 18.4% by accumulation of chronic diseases during the follow-up period. The limitations of this study include unmeasured confounding, self-reported work experience, and the reliance on a psychosocial job-exposure matrix that does not consider variabilities in individuals' perception on working conditions or job characteristics within occupations. CONCLUSIONS: Our findings suggest that negative psychosocial working conditions during working life may accelerate disability progression in later life. Notably, social support at work may buffer the detrimental effect of high strain on disability progression. Cognitive decline and chronic-disease accumulation, and especially the former, partially mediate the association of psychosocial working conditions with trajectories of disability. Further studies are required to explore more mechanisms that underlie the association between psychosocial working conditions and disability trajectories.

Association Between Speed of Multimorbidity Accumulation in Old Age and Life Experiences: A Cohort Study.

Rapidly accumulating multiple chronic conditions (multimorbidity) during aging are associated with many adverse outcomes. We explored the association between 4 experiences throughout life-childhood socioeconomic circumstances, early-adulthood education, midlife occupational stress, and late-life social network-and the speed of chronic disease accumulation. We followed 2,589 individuals aged ≥60 years from the Swedish National Study on Aging and Care in Kungsholmen for 9 years (2001-2013). Information on life experiences was collected from detailed life-history interviews. Speed of disease accumulation was operationalized as the change in the count of chronic conditions obtained from clinical examinations, medical histories, laboratory data, drug use, and register linkages over 9 years. Linear mixed models were used to analyze the data. Speed of disease accumulation was lower in individuals with more than elementary education (for secondary, ß × time = -0.065, 95% CI: -0.126, -0.004; for university, ß × time = -0.118, 95% CI: -0.185, -0.050); for active occupations compared with high-strain jobs (ß × time = -0.078, 95% CI: -0.138, -0.017); and for richer social networks (for moderate tertile, ß × time = -0.102, 95% CI: -0.149, -0.055; for highest tertile, ß × time = -0.135, 95% CI: -0.182, -0.088). The association between childhood circumstances and speed of disease accumulation was attenuated by later-life experiences. Diverse experiences throughout life might decelerate chronic disease accumulation during aging.

Sleep disturbances and dementia risk: A multicenter study.

INTRODUCTION: Few longitudinal studies assessed whether sleep disturbances are associated with dementia risk. METHODS: Sleep disturbances were assessed in three population-based studies (H70 study and Kungsholmen Project [Sweden]; Cardiovascular Risk Factors, Aging and Dementia study [Finland]). Late-life baseline analyses (3-10 years follow-up) used all three studies (N = 1446). Baseline ages ≈ 70 years (Cardiovascular Risk Factors, Aging and Dementia, H70), and ≈84 years (Kungsholmen Project). Midlife baseline (age ≈ 50 years) analyses used Cardiovascular Risk Factors, Aging and Dementia (21 and 32 years follow-up) (N = 1407). RESULTS: Midlife insomnia (fully adjusted hazard ratio = 1.24, 95% confidence interval = 1.02-1.50) and late-life terminal insomnia (fully adjusted odds ratio = 1.94, 95% confidence interval = 1.08-3.49) were associated with a higher dementia risk. Late-life long sleep duration (>9 hours) was also associated with an increased dementia risk (adjusted odds ratio = 3.98, 95% confidence interval = 1.87-8.48). DISCUSSION: Midlife insomnia and late-life terminal insomnia or long sleep duration were associated with a higher late-life dementia risk.

Association of lifelong exposure to cognitive reserve-enhancing factors with dementia risk: A community-based cohort study.

BACKGROUND: Variation in the clinical manifestation of dementia has been associated with differences in cognitive reserve, although less is known about the cumulative effects of exposure to cognitive reserve factors over the life course. We examined the association of cognitive reserve-related factors over the lifespan with the risk of dementia in a community-based cohort of older adults. METHODS AND FINDINGS: Information on early-life education, socioeconomic status, work complexity at age 20, midlife occupation attainment, and late-life leisure activities was collected in a cohort of dementia-free community dwellers aged 75+ y residing in the Kungsholmen district of Stockholm, Sweden, in 1987-1989. The cohort was followed up to 9 y (until 1996) to detect incident dementia cases. To exclude preclinical phases of disease, participants who developed dementia at the first follow-up examination 3 y after the baseline were excluded (n = 602 after exclusions). Structural equation modelling was used to generate latent factors of cognitive reserve from three periods over the life course: early (before 20 y), adulthood (around 30-55 y), and late life (75 y and older). The correlation between early- and adult-life latent factors was strong (γ = 0.9), whereas early-late (γ = 0.27) and adult-late (γ = 0.16) latent factor correlations were weak. One hundred forty-eight participants developed dementia during follow-up, and 454 remained dementia-free. The relative risk (RR) of dementia was estimated using Cox models with life-course cognitive reserve-enhancing factors modelled separately and simultaneously to assess direct and indirect effects. The analysis was repeated among carriers and noncarriers of the apolipoprotein E (APOE) ε4 allele. A reduced risk of dementia was associated with early- (RR 0.57; 95% CI 0.36-0.90), adult- (RR 0.60; 95% CI 0.42-0.87), and late-life (RR 0.52; 95% CI 0.37-0.73) reserve-enhancing latent factors in separate multivariable Cox models. In a mutually adjusted model, which may have been imprecisely estimated because of strong correlation between early- and adult-life factors, the late-life factor preserved its association (RR 0.65; 95% CI 0.45-0.94), whereas the effect of midlife (RR 0.73; 95% CI 0.50-1.06) and early-life factors (RR 0.76; 95% CI 0.47-1.23) on the risk of dementia was attenuated. The risk declined progressively with cumulative exposure to reserve-enhancing latent factors, and having high scores on cognitive reserve-enhancing composite factors in all three periods over the life course was associated with the lowest risk of dementia (RR 0.40; 95% CI 0.20-0.81). Similar associations were detected among APOE ε4 allele carriers and noncarriers. Limitations include measurement error and nonresponse, with both biases likely favouring the null. Strong correlation between early- and adult-life latent factors may have led to a loss in precision when estimating mutually adjusted effects of all periods. CONCLUSIONS: In this study, cumulative exposure to reserve-enhancing factors over the lifespan was associated with reduced risk of dementia in late life, even among individuals with genetic predisposition.

Personality and Survival in Older Age: The Role of Lifestyle Behaviors and Health Status.

OBJECTIVE: We intended to assess the relationship between personality and survival in an older population and to explore the role of lifestyle behaviors and health status as potential mediators. DESIGN: Population-based cohort study. SETTING: Swedish National Study of Aging and Care in Kungsholmen, Sweden. PARTICIPANTS: 2,298 adults aged 60 or more years, without dementia or depression, followed for 11 years. MEASUREMENTS: Personality (extraversion, neuroticism, and openness) was assessed with a shortened version of the NEO-Five Factor Inventory. We tested whether personality affected mortality and examined the potential mediating effect of health status (body mass index, number of chronic diseases, impairment in instrumental activities of daily living, and C-reactive protein) and lifestyle behaviors (leisure activities, social network, smoking, and alcohol consumption). RESULTS: Over 11 years of follow-up, higher levels of extraversion were associated with a 14% reduction in mortality. Examination of different combinations of personality traits showed that independent of levels of neuroticism and openness, high extraversion were associated with up to 65% lower mortality. Decomposing the effect of extraversion on mortality, we found that the majority (44%) of the beneficial effect was mediated by healthy lifestyle behaviors. Health status accounted for 5% of the association. CONCLUSIONS: Extroverted people, who are characterized by higher optimism and high self-efficacy, are prone to healthier behaviors and better health, which may result in longer survival. These results highlight the importance of a healthy lifestyle in survival.

Influence of Negative Life Events and Widowhood on Risk for Dementia.

OBJECTIVE: The aim of the current study was to examine the effect of negative life events and widowhood on the incidence of dementia. METHODS: Data were from four Swedish longitudinal cohort studies with a total of nearly 2,000 participants and 8-25 years of follow-up. Seven stressful events were examined for which data were available in all cohorts. Clinical dementia diagnoses were made through medical and psychological examinations. Cox proportional hazards models were used to estimate the association between life events and dementia, adjusting for lifestyle and cardiovascular risk factors. RESULTS: The experience of one stressful life event was not associated with dementia incidence, but two or more negative life events at baseline predicted higher risk for dementia (pooled HR: 2.00). This was most apparent for the incidence of vascular dementia (pooled HR: 3.60) but not for Alzheimer disease (pooled HR: 1.29). Moreover, persons who were widowed and had experienced one or more negative life events were found to have a threefold risk for dementia. CONCLUSION: Widowhood augments the effect of negative life events on dementia incidence and negative life events specifically increase the risk for vascular dementia.

HHEX_23 AA Genotype Exacerbates Effect of Diabetes on Dementia and Alzheimer Disease: A Population-Based Longitudinal Study.

BACKGROUND: Research has suggested that variations within the IDE/HHEX gene region may underlie the association of type 2 diabetes with Alzheimer disease (AD). We sought to explore whether IDE genes play a role in the association of diabetes with dementia, AD, and structural brain changes using data from two community-based cohorts of older adults and a subsample with structural MRI. METHODS AND FINDINGS: The first cohort, which included dementia-free adults aged ≥75 y (n = 970) at baseline, was followed for 9 y to detect incident dementia (n = 358) and AD (n = 271) cases. The second cohort (for replication), which included 2,060 dementia-free participants aged ≥60 y at baseline, was followed for 6 y to identify incident dementia (n = 166) and AD (n = 121) cases. A subsample (n = 338) of dementia-free participants from the second cohort underwent MRI. HHEX_23 and IDE_9 were genotyped, and diabetes (here including type 2 diabetes and prediabetes) was assessed. In the first cohort, diabetes led to an adjusted hazard ratio (HR) of 1.73 (95% CI 1.19-2.32) and 1.66 (95% CI 1.06-2.40) for dementia and AD, respectively, among all participants. Compared to people carrying the GG genotype without diabetes, AA genotype carriers with diabetes had an adjusted HR of 5.54 (95% CI 2.40-7.18) and 4.81 (95% CI 1.88-8.50) for dementia and AD, respectively. There was a significant interaction between HHEX_23-AA and diabetes on dementia (HR 4.79, 95% CI 1.63-8.90, p = 0.013) and AD (HR 3.55, 95% CI 1.45-9.91, p = 0.025) compared to the GG genotype without diabetes. In the second cohort, the HRs were 1.68 (95% CI 1.04-2.99) and 1.64 (1.02-2.33) for the diabetes-AD and dementia-AD associations, respectively, and 4.06 (95% CI 1.06-7.58, p = 0.039) and 3.29 (95% CI 1.02-8.33, p = 0.044) for the interactions, respectively. MRI data showed that HHEX_23-AA carriers with diabetes had significant structural brain changes compared to HHEX_23-GG carriers without diabetes. No joint effects of IDE_9 and diabetes on dementia were shown. As a limitation, the sample sizes were small for certain subgroups. CONCLUSIONS: A variant in the HHEX_23 gene interacts with diabetes to be associated with a substantially increased risk of dementia and AD, and with structural brain changes among dementia-free elderly people.

A Life-Course Study of Cognitive Reserve in Dementia--From Childhood to Old Age.

OBJECTIVE: To test a life-course model of cognitive reserve in dementia and examine if school grades around age 10 years, formal educational attainment, and lifetime occupational complexity affect the risk of dementia in old age. METHODS: 7,574 men and women from the Uppsala Birth Cohort Multigenerational Study were followed for 21 years. Information on school performance, formal education, and occupational attainment was collected prospectively from elementary school archives and population censuses. Dementia diagnosis was extracted from the two Swedish registers. Discrete-time Cox proportional hazard models were estimated. RESULTS: Dementia was diagnosed in 950 individuals (12.5%). Dementia risk was lower among individuals with higher childhood school grades (hazard ratio [HR]: 0.79; 95% confidence interval [CI]: 0.68 to 0.93) and was lower among individuals in data-complex occupations (HR: 0.77; 95% CI: 0.64 to 0.92). Professional/university education predicted lower risk of dementia in minimally adjusted models (HR: 0.74; 95% CI: 0.60 to 0.91), although the effect faded with adjustment for occupational complexity. Lowest risk was found in the group with both higher childhood school performance and high occupational complexity with data (HR: 0.61; 95% CI: 0.50 to 0.75). Importantly, high occupational complexity could not compensate for the effect of low childhood grades. In contrast, dementia risk was reduced in those with higher school grades, irrespective of occupational complexity. CONCLUSION: Higher childhood school performance is protective of dementia risk, particularly when preserved through complex work environments in adulthood, although it will remain protective even in the absence of later-life educational or occupational stimulation.

Do levels of perceived stress increase with increasing age after age 65? A population-based study.

BACKGROUND: psychological and health-related stressors often occur in advanced ages, but little is known about perceived stress in adults aged 65 and over. This study aimed to test the hypothesis that levels of perceived stress increase with increasing age and to detect factors that may account for the association. METHODS: a dementia-free cohort of 1,656 adults aged 66-97 years living at home or in institutions, participating in the Swedish National Aging and Care study, Kungsholmen (SNAC-K) was assessed for levels of perceived stress using the 10-item perceived stress scale (PSS). RESULTS: prevalence of high stress according to the top tertile of the population (PSS score 20+) was 7.8% in adults aged 81+ years, 7.5% in adults aged 72-78 and 6.2% in adults aged 66 years (P = 0.020). More women than men reported high stress, 8.3 versus 5.4% (P = 0.001). Levels of stress increased with increasing age (P = 0.001) in the linear regression model. This association remained after adjustment for demographic and psychosocial factors, but no longer was present after adjusting for health-related factors. CONCLUSION: health-related stress is highly prevalent in older adults and seems to play an important role in the association between levels of perceived stress and age in older adults.

A change in sleep pattern may predict Alzheimer disease.

OBJECTIVE: Sleep problems may adversely affect neuronal health. We examined a subjective report of change (reduced duration and/or depth) in sleep pattern in relation to subsequent risk of incident all-cause dementia and Alzheimer disease (AD) over 9 years. METHODS: This longitudinal study used data from a population-based sample of 214 Swedish adults aged 75 and over who were dementia-free both at baseline and at first follow-up (3 years later). The sample was 80% female and, on average, 83.4 years of age at baseline. All participants underwent a thorough clinical examination to ascertain all-cause dementia and AD. RESULTS: Forty percent of participants reported a change in sleep duration at baseline. Between the 6th and 9th year after baseline, 28.5% were diagnosed with all-cause dementia, 22.0% of whom had AD. Reduced sleep was associated with a 75% increased all-cause dementia risk (hazard ratio: 1.75; 95% confidence interval: 1.04-2.93; Wald = 4.55, df = 1, p = 0.035) and double the risk of AD (hazard ratio: 2.01; 95% confidence interval: 1.12-3.61; Wald = 5.47, df = 1, p = 0.019) after adjusting for age, gender, and education. The results remained after adjusting for lifestyle and vascular factors but not after adjusting for depressive symptoms. No evidence supported a moderating effect of the use of sleeping pills, and the sleep-dementia relationship remained after controlling for the presence of the apolipoprotein E ε4 allele. CONCLUSION: Self-reported sleep problems may increase the risk for dementia, and depressive symptoms may explain this relationship. Future research should determine whether treatment, in particular, behavioral or nonpharmacologic treatment, may represent one avenue toward reduction of dementia risk in late life.

[Cell-penetrating chimeric apoptotic peptide AVPI-LMWP/DNA co-delivery system for cancer therapy].

To develop a cell-penetrating chimeric apoptotic peptide AVPI-LMWP/DNA co-delivery system for cancer therapy, we prepared the AVPI-LMWP/pTRAIL self-assembled complexes containing a therapeutic combination of peptide drug AVPI and DNA drug TRAIL. The chimeric apoptotic peptide AVPI-LMWP was synthesized using the standard solid-phase synthesis. The cationic AVPI-LMWP could condense pTRAIL by electrostatic interaction. The physical-chemical properties of the AVPI-LMWP/pTRAIL complexes were characterized. The cellular uptake efficiency and the inhibitory activity of the AVPI-LMWP/pTRAIL complexes on tumor cell were also performed. The results showed that the AVPI-LMWP/pTRAIL complexes were successfully prepared by co-incubation. With the increase of mass ratio (AVPI-LMWP/DNA), the particle size was decreased and the zeta potential had few change. Agarose gel electrophoresis showed that AVPI-LMWP could fully bind and condense pTRAIL at a mass ratio above 15:1. Cellular uptake efficiency was improved along with the increased ratio of W(AVPI-LMWP)/WpTRAIL. The in vitro cytotoxicity experiments demonstrated that the AVPI-LMWP/pTRAIL (W:W = 20:1) complexes was significantly more effective than the pTRAIL, AVPI-LMWP alone or LMWP/pTRAIL complexes on inhibition of HeLa cell growth. Our studies indicated that the AVPI-LMWP/pTRAIL co-delivery system could deliver plasmid into HeLa cell and induce tumor cell apoptosis efficiently, which showed its potential in cancer therapy using combination of apoptoic peptide and gene drugs.

[Clinical characteristics of whooping cough in neonates and antimicrobial resistance of the pathogenic bacteria].

OBJECTIVE: To study the clinical characteristics of whooping cough in neonates and the antimicrobial resistance of the bacterial isolates. METHODS: Clinical information of 7 neonates with whooping cough confirmed by bacterial culture was collected. The antimirobial resistance of the isolates was tested using E-test and disk diffusion methods. RESULTS: The children′s mothers or other family members had cough for more than 10 days in 6 neonates, in which four neonates contacted with 3 or more family members with cough. All the neonates had rhinobyon and slight cough at the beginning of the disease. Five cases presented typical spasmodic cough after 4-7 days of the onset. Five cases displayed cyanosis, four cases occurred apnea, three cases suffered breath holding, and only two cases had fever. Nares flaring and three depression signs were found in the physical examination. No bacteriostatic ring around the erythromycin disks were found for five bacterial isolates. The minimal inhibitory concentration (MIC) for erythromycin, azithromycin, clarithromycin and clindamycin were all >256 mg/L against the five isolates. CONCLUSIONS: Whooping cough should be considered for neonates with respiratory symptoms and a history of close contact with respiratory infection patients. Macrolide-resistant Bordetella pertussis is common in children with whooping cough.