The Effect of Diagnostic Criteria on Dementia Prevalence - A Population-Based Study From Gothenburg, Sweden.

OBJECTIVES: To examine how the use of different diagnostic criteria (Diagnostic and Statistical Manual of Mental Disorders third revised, fourth, and fifth editions [DSM-III-R, DSM-IV, and DSM-5], and the 10th and 11th editions of the International Classification of Diseases [ICD-10 and ICD-11] influences the reported prevalence of dementia. METHODS: Two cross-sectional population-based studies of systematically selected 85-year-olds in Gothenburg, Sweden, (N = 774), were examined in comprehensive health examinations including comprehensive neurocognitive examinations. Five algorithms based on the diagnostic criteria in the DSM-III-R, DSM-IV, DSM-5, ICD-10, and ICD-11 were created, including 105 different variables that were operationalized in different ways to match the criteria of each classification system. RESULTS: ICD-11 yielded the highest prevalence of dementia (36.4%), followed by DSM-5 (32.9%), DSM-IV (30.7%), the clinical consensus DSM-III-R diagnosis (26.7%), DSM-III-R (21.4%), and ICD-10 (20.5%). The agreement between the DSM-5 and the ICD-11 was κ = 0.9. All other kappa values ranged between 0.6 and 0.9. CONCLUSIONS: The choice of diagnostic criteria has a large effect on the estimated prevalence of dementia. We found that the recent editions, the DSM-5 and ICD-11, gave a higher prevalence of dementia than older editions. We also show that the attempts to harmonize DSM and ICD have in part been successful, however, there are still differences between the systems.

The natural history of lifetime psychiatric disorders in patients with obsessive-compulsive disorder followed over half a century.

OBJECTIVE: Few long-term studies have examined the life-time prevalence of comorbid psychiatric conditions in patients with obsessive-compulsive disorder (OCD). We therefore studied the frequency of comorbid psychiatric disorders, and their relation to onset and prognosis, in patients with OCD who were followed for almost half a century. METHODS: During 1947-1953, 285 OCD patients were admitted as inpatients to a university hospital in Gothenburg, Sweden. Among those, 251 (88%) accepted a structured comprehensive psychiatric examination in 1954-1956. In 1989-1993, 176 survivors were eligible and 144 (response rate 82%) were re-examined. The same psychiatrist performed both examinations. OCD was diagnosed according to the Schneider criteria, and other mental disorders according to DSM-IV. Mean follow-up since onset was 47 years. RESULTS: The lifetime frequency of depressive disorders was 84.7% (major depression 43.8%), generalized anxiety disorder (GAD) 71.5%, panic anxiety disorder 47.9%, agoraphobia 52.1%, specific phobias 64.6%, social phobia 47.9%, paranoid conditions 40.3% (29.1% paranoid ideation), psychotic disorders 15.3%, alcohol abuse 13.2% (men 39%, women 3%) and substance abuse 17.4%. Specific phobia most often started before OCD, while depression had a varied onset in relation to OCD. Social phobia, agoraphobia, GAD, alcohol and substance abuse, psychotic disorders and paranoid conditions most often started after OCD. Presence of GAD, psychotic disorder and substance abuse worsened prognosis of OCD. CONCLUSION: Comorbid psychiatric conditions are common in OCD patients, and have onset throughout the course. OCD signals vulnerability for other psychiatric conditions, which are important to detect in clinical practice as they negatively affect the outcome.

Effects of current alcohol use on brain volume among older adults in the Gothenburg H70 Birth Cohort study 2014-16.

Brain gray- and white matter changes is well described in alcohol-dependent elderly subjects; however, the effect of lower levels of alcohol consumption on the brain is poorly understood. We investigated the impact of different amounts of weekly alcohol consumption on brain structure in a population-based sample of 70-year-olds living in Gothenburg, Sweden. Cross-sectional data from 676 participants from The Gothenburg H70 Birth Cohort Study 2014-16 were included. Current alcohol consumers were divided into seven groups based on self-reported weekly amounts of alcohol consumption in grams (g) (0-50 g/week, used as reference group, 51-100 g/week, 101-150 g/week, 151-200 g/week, 201-250 g/week, 251-300 g/week, and > 300 g/week). Subcortical volumes and cortical thickness were assessed on T1-weighted structural magnetic resonance images using FreeSurfer 5.3, and white matter integrity assessed on diffusion tensor images, using tract-based statistics in FSL. General linear models were carried out to estimate associations between alcohol consumption and gray- and white matter changes in the brain. Self-reported consumption above 250 g/week was associated with thinning in the bilateral superior frontal gyrus, the right precentral gyrus, and the right lateral occipital cortex, in addition to reduced fractional anisotropy (FA) and increased mean diffusivity (MD) diffusively spread in many tracts all over the brain. No changes were found in subcortical gray matter structures. These results suggest that there is a non-linear relationship between alcohol consumption and structural brain changes, in which loss of cortical thickness only occur in non-demented 70-year-olds who consume more than 250 g/week.

Midlife stress-related exhaustion and dementia incidence: a longitudinal study over 50 years in women.

BACKGROUNDS: Cognitive problems are common symptoms among individuals with stress-related exhaustion. It is still unknown whether these individuals are at a higher risk of developing dementia later. This study aims to examine the relationship between midlife stress-related exhaustion and dementia incidence. METHODS: A population sample of 777 women (aged 38, 46, 50 and 54 years) without dementia at baseline was followed over 50 years, from 1968 to 2019. Stress-related exhaustion was based on information from the psychiatric examination in 1968/69. Information on dementia incidence between 1968 and 2019 was obtained from neuropsychiatric examinations, key-informant interviews, and hospital registry. Dementia was diagnosed according to the DSM-III-R criteria. A subgroup of non-demented women (n = 284) was examined for cognitive functions by the Gottfries-Bråne-Steen scale 24 years after baseline. RESULTS: Stress-related exhaustion in midlife was associated with higher risk for development of dementia before age 75 (Hazard ratio and 95% confidence interval: 2.95 and 1.35-6.44). The association remained after adjustment for age, major depression, and anxiety disorder. Mean age of dementia onset was younger for women with stress-related exhaustion than women without stress (mean ± SD, 76 ± 9 vs. 82 ± 8 . p = 0.009). Women with stress-related exhaustion in midlife still showed more cognitive impairments 24 years later compared with women without stress (Odds ratio and 95% confidence interval: 2.64 and 1.15-6.06). CONCLUSIONS: We found that women with stress-related exhaustion in midlife were at a higher risk to develop dementia at relatively younger age. These women showed persistently lower cognitive functions over years even without dementia. Present study results need to be interpreted with caution due to small sample size and should be confirmed in future studies with larger sample size. Our study findings may imply the importance of long-term follow-up regarding cognitive function among individuals with stress-related exhaustion.

Genetic variants in the FOXO1 and ZNF469 genes are associated with keratoconus in Sweden: a case-control study.

BACKGROUND: Keratoconus (KC) is characterized by pathological thinning and bulging of the cornea that may lead to visual impairment. The etiology of sporadic KC remains enigmatic despite intensive research in recent decades. The purpose of this study was to examine the relationship between previously highlighted genetic variants associated with KC and sporadic KC in a Swedish cohort. METHODS: A total of 176 patients (age 16-70 years) with sporadic KC diagnosed by Scheimpflug-topography (Pentacam) were included. The control group (n = 418; age 70 years) was a subsample originating from the Gothenburg H70 Birth Cohort Studies of ageing. Extraction of DNA from blood samples was performed according to standard procedures, and genotyping was performed using competitive allele specific PCR (KASP) technology. A total of 11 single nucleotide polymorphisms (SNPs) were selected for analysis. RESULTS: Statistically significant associations (p = 0.005) were found between the SNPs rs2721051 and rs9938149 and sporadic KC. These results replicate earlier research that found associations between genetic variants in the FOXO1 and BANP-ZNF469 genes and sporadic KC in other populations. CONCLUSION: Genetic variations in the FOXO1 and BANP-ZNF469 genes may be involved in the pathogenesis of sporadic KC.

Hearing acuity in nonagenarians aged 90 and 95 assessed in a home setting using standardized pure-tone audiometry.

OBJECTIVE: Knowledge regarding hearing acuity in the nonagenarian age group is sparse. In this study we aimed to advance our understanding of hearing loss in the 10th decade of life. DESIGN: A cross-sectional study in which standardised hearing measurements were performed during home visits, which included care home facilities and nursing homes to maximise participation. STUDY SAMPLE: Two unselected groups of individuals aged 90 (n = 42) and 95 (n = 49), sampled from the population-based Gothenburg H70 Birth Cohort Studies. RESULTS: 98% of the participants (95% CI [95, 100]) had some degree of hearing loss in their better ear, with 83% (95% CI [73, 89]) having a potentially disabling hearing loss of moderate degree or worse, according to WHO criteria. Furthermore, differences between the two age groups (five years apart) indicate an increasing hearing loss, primarily at frequencies ≥ 2 kHz. CONCLUSION: Hearing loss was present in almost all of the participants in the nonagenarian age group and among a majority of them potentially to a degree that would warrant rehabilitation. Carrying out standardised hearing measurements in a home setting was feasible in this age group and enhanced the representativeness of the study population.

Bilateral hearing loss affected almost all of the individuals in the nonagenarian age group with 8 in 10 having hearing loss of a degree severe enough to warrant intervention or hearing aid prescription.The findings provide valuable insight into hearing acuity among nonagenarians. Many earlier studies were limited to subjective hearing assessments, reviews of medical records and/or screening tests performed by non-audiologists.The final sample size was smaller than initially planned due to the COVID-19 pandemic. However, measures were taken to optimise the representativeness of the study sample.

CT-based volumetric measures obtained through deep learning: Association with biomarkers of neurodegeneration.

INTRODUCTION: Cranial computed tomography (CT) is an affordable and widely available imaging modality that is used to assess structural abnormalities, but not to quantify neurodegeneration. Previously we developed a deep-learning-based model that produced accurate and robust cranial CT tissue classification. MATERIALS AND METHODS: We analyzed 917 CT and 744 magnetic resonance (MR) scans from the Gothenburg H70 Birth Cohort, and 204 CT and 241 MR scans from participants of the Memory Clinic Cohort, Singapore. We tested associations between six CT-based volumetric measures (CTVMs) and existing clinical diagnoses, fluid and imaging biomarkers, and measures of cognition. RESULTS: CTVMs differentiated cognitively healthy individuals from dementia and prodromal dementia patients with high accuracy levels comparable to MR-based measures. CTVMs were significantly associated with measures of cognition and biochemical markers of neurodegeneration. DISCUSSION: These findings suggest the potential future use of CT-based volumetric measures as an informative first-line examination tool for neurodegenerative disease diagnostics after further validation. HIGHLIGHTS: Computed tomography (CT)-based volumetric measures can distinguish between patients with neurodegenerative disease and healthy controls, as well as between patients with prodromal dementia and controls. CT-based volumetric measures associate well with relevant cognitive, biochemical, and neuroimaging markers of neurodegenerative diseases. Model performance, in terms of brain tissue classification, was consistent across two cohorts of diverse nature. Intermodality agreement between our automated CT-based and established magnetic resonance (MR)-based image segmentations was stronger than the agreement between visual CT and MR imaging assessment.

Lifestyle and incident dementia: A COSMIC individual participant data meta­analysis.

INTRODUCTION: The LIfestyle for BRAin Health (LIBRA) index yields a dementia risk score based on modifiable lifestyle factors and is validated in Western samples. We investigated whether the association between LIBRA scores and incident dementia is moderated by geographical location or sociodemographic characteristics. METHODS: We combined data from 21 prospective cohorts across six continents (N = 31,680) and conducted cohort-specific Cox proportional hazard regression analyses in a two-step individual participant data meta-analysis. RESULTS: A one-standard-deviation increase in LIBRA score was associated with a 21% higher risk for dementia. The association was stronger for Asian cohorts compared to European cohorts, and for individuals aged ≤75 years (vs older), though only within the first 5 years of follow-up. No interactions with sex, education, or socioeconomic position were observed. DISCUSSION: Modifiable risk and protective factors appear relevant for dementia risk reduction across diverse geographical and sociodemographic groups. HIGHLIGHTS: A two-step individual participant data meta-analysis was conducted. This was done at a global scale using data from 21 ethno-regionally diverse cohorts. The association between a modifiable dementia risk score and dementia was examined. The association was modified by geographical region and age at baseline. Yet, modifiable dementia risk and protective factors appear relevant in all investigated groups and regions.

Polygenic risk scores for Alzheimer's disease in relation to cognitive change: A representative sample from the general population followed over 16 years.

BACKGROUND: Polygenic risk scores for Alzheimer's disease (AD-PRSs) have been associated with cognition. However, few studies have examined the effect of AD-PRS beyond the APOE gene, and the influence of genetic variants related to level of cognitive ability (COG-PRS) on cognitive performance over time in the general older population. METHOD: A population-based sample of 965 individuals born in 1930, with genetic and standardized cognitive data on six psychometric tests (Thurstone's picture memory, immediate recall of 10 words, Block design, word fluency, figure identification, delayed recall of 12 items), were examined at age 70, 75, 79, and 85 years. Non-APOE AD-PRSs and COG-PRSs (P < 5e-8, P < 1e-5, P < 1e-3, P < 1e-1) were generated from recent genome-wide association studies. Linear mixed effect models with random intercepts and slope were used to analyze the effect of APOE ε4 allele, AD-PRSs, and COG-PRSs, on cognitive performance and rate of change. Analyses were repeated in samples excluding dementia. RESULTS: APOE ε4 and AD-PRS predicted change in cognitive performance (APOE ε4*age: ß = -0.03, P < 0.0001 and AD-PRS *age: ß = -0.01, P = 0.02). The results remained similar in the sample excluding those with dementia. COG-PRS predicted level of cognitive performance, while APOE ε4 and AD-PRS did not. COG-PRSs did not predict change in cognitive performance. CONCLUSION: We found that genetic predisposition of AD predicted cognitive decline among 70-year-olds followed over 16 years, regardless of dementia status, while polygenic risk for general cognitive performance did not.

Time trends in depression prevalence among Swedish 85-year-olds: repeated cross-sectional population-based studies in 1986, 2008, and 2015.

BACKGROUND: Octogenarians of today are better educated, and physically and cognitively healthier, than earlier born cohorts. Less is known about time trends in mental health in this age group. We aimed to study time trends in the prevalence of depression and psychotropic drug use among Swedish 85-year-olds. METHODS: We derived data from interviews with 85-year-olds in 1986-1987 (N = 348), 2008-2010 (N = 433) and 2015-17 (N = 321). Depression diagnoses were made according to the Diagnostic and Statistical Manual of Mental Disorders. Symptom burden was assessed with the Montgomery-Åsberg Depression Rating Scale (MADRS). Information on psychotropic drug use, sociodemographic, and health-related factors were collected during the interviews. RESULTS: The prevalence of major depression was lower in 2015-2017 (4.7%, p < 0.001) and 2008-2010 (6.9%, p = 0.010) compared to 1986-1987 (12.4%). The prevalence of minor depression was lower in 2015-2017 (8.1%) compared to 2008-2010 (16.2%, p = 0.001) and 1986-1987 (17.8%, p < 0.001). Mean MADRS score decreased from 8.0 in 1986-1987 to 6.5 in 2008-2010, and 5.1 in 2015-2017 (p < 0.001). The reduced prevalence of depression was not explained by changes in sociodemographic and health-related risk factors for depression. While psychoactive drug use was observed in a third of the participants in each cohort, drug type changed over time (increased use of antidepressants and decreased use of anxiolytics and antipsychotics). CONCLUSIONS: The prevalence of depression in octogenarians has declined during the past decades. The decline was not explained by changes in known risk factors for depression. The present study cannot answer whether changed prescription patterns of psychoactive drugs have contributed to the decline.

Life-Weariness, Wish to Die, Active Suicidal Ideation, and All-Cause Mortality in Population-Based Samples of Older Adults.

OBJECTIVES: To investigate potential differences in the strength of associations between different levels of passive and active suicidal ideation and all-cause mortality in older adults. DESIGN: Prospective cohort study. SETTING: Population-based samples of older adults in Gothenburg, Sweden. PARTICIPANTS: Older adults aged 79 and above who participated in any wave of the Gothenburg H70 Birth Cohort Studies or the Prospective Population Study of Women between 1986 and 2015 (n = 2,438; 1,737 women, 701 men; mean age 86.6). MEASUREMENTS: Most intense level of passive or active suicidal ideation during the past month: life-weariness, wish to die, or active suicidal ideation. The outcome was all-cause mortality over 3 years. RESULTS: During follow-up, 672 participants (27.6%) died. After adjustments for sex, age, and year of examination, participants who reported a wish to die (HR 2.01; 95% CI 1.55-2.60) as the most intense level of ideation, but not participants who reported life-weariness (HR 1.40; 95% CI 0.88-2.21) or active suicidal ideation (HR 1.10; 95% CI 0.69-1.76) were at increased risk of all-cause mortality. Reporting a wish to die remained associated with mortality in a fully adjusted model, including somatic conditions, dementia, depression, and loneliness (HR 1.70; 95% CI 1.27-2.26). CONCLUSION: In older adults, reporting a wish to die appears to be more strongly associated with all-cause mortality than either life-weariness or active suicidal ideation.

Mild cognitive impairment is associated with passive suicidal ideation in older adults: A population-based study.

OBJECTIVE: To investigate the association between MCI and passive/active suicidal ideation in a population-based sample of older adults. METHOD: The sample included 916 participants without dementia acquired from the two population-based studies Prospective Population Study of Women (PPSW) and the H70-study. Cognitive status was assessed using a comprehensive neuropsychiatric examination and classified according to the Winblad et al. criteria: 182 participants were classified as cognitively intact, 448 had cognitive impairment but did not fulfill MCI criteria and 286 were diagnosed with MCI. Passive/active suicidal ideation was assessed using the Paykel questions. RESULTS: Passive or active suicidal ideation (any level) was reported by 16.0% of those with MCI and 1.1% of those who were cognitively intact. MCI was associated with past year life-weariness (OR 18.32, 95% CI 2.44-137.75) and death wishes (OR 5.30, 95% CI 1.19-23.64) in regression models adjusted for covariates including major depression. Lifetime suicidal ideation was reported more frequently in MCI (35.7%) than in cognitively intact participants (14.8%). MCI was associated with lifetime life-weariness (OR 2.90, 95% CI 1.67-5.05). Among individuals with MCI, impairments in memory and visuospatial ability were associated with both past year and lifetime life-weariness. CONCLUSION: Our findings suggest reports of past year as well as lifetime passive suicidal ideation to be more frequent among individuals with MCI compared to those cognitively intact, indicating that individuals with MCI may constitute a high-risk group for suicidal behavior.

Alcohol use and drinking patterns in Swedish 85 year olds born three decades apart - findings from the Gothenburg H70 study.

BACKGROUND: Little is known about alcohol consumption among the oldest old. OBJECTIVE: To compare alcohol use and drinking patterns among 85 year olds born three decades apart. DESIGN: Cross-sectional. SETTING: The Gothenburg H70 Birth Cohort Studies. SUBJECTS: About 1,160 85 year olds born in 1901-02, 1923-24, and 1930. METHODS: Self-reported questions about alcohol included how often study participants drank beer, wine, and spirits and how many centilitres in total/week. Risk consumption was defined as ≥100 g alcohol/week. Descriptive statistics and logistic regression were used to explore cohort characteristics, differences in proportions, factors associated with risk consumption and 3-year mortality. RESULTS: The proportion of at-risk drinkers increased from 4.3 to 14.9% (9.6-24.7% in men and 2.1-9.0% in women). The proportion of abstainers decreased from 27.7 to 12.9%, with the largest decrease observed among women (29.3-14.1%). Controlling for sex, education and marital status, 85 year olds in the later-born cohorts were more likely to be risk consumers than those in the earlier-born cohort [odds ratio (OR) 3.1, 95% confidence nterval (CI) 1.8-5.6]. The only factor associated with an increased likelihood was male sex (OR 3.7, 95% CI 1.0-12.7 and OR 3.2, 95% CI 2.0-5.1). There were no associations between risk consumption of alcohol and 3-year mortality in any of the cohorts. CONCLUSION: Alcohol consumption and the number of risk consumers among 85 year olds have increased considerably. This could have large public health consequences since older adults are more sensitive to alcohol's adverse health effects. Our findings show the importance of detecting risk drinkers also in the oldest old.

Hearing Loss and Cognitive Function in Early Old Age: Comparing Subjective and Objective Hearing Measures.

INTRODUCTION: Population-based research has consistently shown that people with hearing loss are at greater risk of cognitive impairment. We aimed to explore the cross-sectional association of both subjective and objective hearing measures with global and domain-specific cognitive function. We also examined the influence of hearing aid use on the relationship. METHODS: A population-based sample (n = 1,105, 52% women) of 70-year-olds that were representative of the inhabitants of the city of Gothenburg, Sweden completed a detailed cognitive examination, pure-tone audiometry, and a questionnaire regarding perceived hearing problems. A subsample (n = 247, 52% women) also completed a test of speech-recognition-in-noise (SPRIN). Multiple linear regression analyses were conducted to explore the association of hearing with cognitive function, adjusting for sex, education, cardiovascular factors, and tinnitus. RESULTS: Global cognitive function was independently associated with the better ear pure-tone average across 0.5-4 kHz (PTA4, ß = -0.13, 95% CI, -0.18, -0.07), the better ear SPRIN score (ß = 0.30, 95% CI, 0.19, 0.40), but not with the self-reported hearing measure (ß = -0.02, 95% CI, -0.07, 0.03). Both verbally loaded and nonverbally loaded tasks, testing a variety of cognitive domains, contributed to the association. Hearing aid users had better global cognitive function than nonusers with equivalent hearing ability. The difference was only significant in the mild hearing loss category. DISCUSSION: In a population-based sample of 70-year-old persons without dementia, poorer hearing was associated with poorer global and domain-specific cognitive function, but only when hearing function was measured objectively and not when self-reported. The speech-in-noise measure showed the strongest association. This highlights the importance of including standardized hearing tests and controlling for hearing status in epidemiological geriatric research. More research is needed on the role that hearing aid use plays in relation to age-related cognitive declines.

The effect of alcohol consumption on all-cause mortality in 70-year-olds in the context of other lifestyle risk factors: results from the Gothenburg H70 birth cohort study.

BACKGROUND: In this study, we examined the effect of alcohol, as well as the combined effect of seven lifestyle factors, on all-cause mortality in older adults (baseline age 70 years). METHODS: Data was derived from the population-based Gothenburg H70 Birth Cohort study, including 1124 participants from the 2014-16 examination. Risk consumption was defined as > 98 g alcohol per week, and hazardous drinking was based on the Alcohol Use Disorders Identification Test-Consumption questionnaire (AUDIT-C). Cox regression models were used to examine the individual effect of alcohol consumption, as well as the combined effect of seven lifestyle risk factors (high alcohol consumption, lifetime smoking, unhealthy Body Mass Index, insufficient physical activity, sedentary behavior, insufficient/prolonged sleep, unhealthy dietary pattern) on all-cause mortality. RESULTS: During a mean follow-up of 7.7 years, 81 (7.2%) participants died. Neither risk consumption nor hazardous drinking were associated with elevated mortality, but hazardous drinking was associated with an increased risk of mortality in those with insufficient physical activity. Those with at least five lifestyle risk factors had an increased all-cause mortality compared to those fulfilling criteria for a maximum of one lifestyle risk factor. High alcohol consumption showed a relatively minor impact on this risk, while physical activity and unhealthy dietary pattern had an independent effect on mortality. CONCLUSIONS: In this particular sample, there was no independent effect of alcohol on the risk of 8-year all-cause mortality. However, an interaction effect of physical activity was observed. It may be that high alcohol consumption per se is less important for mortality among older adults. However, a combination of several unhealthy lifestyle behaviors was linked to a substantial increase in the risk of mortality in Swedish older adults. Also, it has to be emphasized that high alcohol consumption may have other adverse health effects apart from mortality among older adults.

Six-year mortality associated with living alone and loneliness in Swedish men and women born in 1930.

BACKGROUND: This study examined how living alone and loneliness associate with all-cause mortality in older men and women. METHODS: Baseline data from the Gothenburg H70 Birth Cohort Studies, including 70-year-olds interviewed in 2000 and 75-year-olds (new recruits) interviewed in 2005 were used for analyses (N = 778, 353 men, 425 women). Six-year mortality was based on national register data. RESULTS: At baseline, 36.6% lived alone and 31.9% reported feelings of loneliness. A total of 72 (9.3%) participants died during the 6-year follow-up period. Cumulative mortality rates per 1000 person-years were 23.9 for men and 9.6 for women. Mortality was increased more than twofold among men who lived alone compared to men living with someone (HR 2.40, 95% CI 1.34-4.30). Elevated risk remained after multivariable adjustment including loneliness and depression (HR 2.56, 95% CI 1.27-5.16). Stratification revealed that mortality risk in the group of men who lived alone and felt lonely was twice that of their peers who lived with someone and did not experience loneliness (HR 2.52, 95% CI 1.26-5.05). In women, a more than fourfold increased risk of mortality was observed in those who experienced loneliness despite living with others (HR 4.52, 95% CI 1.43-14.23). CONCLUSIONS: Living alone was an independent risk factor for death in men but not in women. Mortality was doubled in men who lived alone and felt lonely. In contrast, mortality was particularly elevated in women who felt lonely despite living with others. In the multivariable adjusted models these associations were attenuated and were no longer significant after adjusting for mainly depression in men and physical inactivity in women. Gender needs to be taken into account when considering the health consequences of living situation and loneliness.

Parental history of dementia and the risk of dementia: A cross-sectional analysis of a global collaborative study.

BACKGROUND: Parental history of dementia appears to increase the risk of dementia, but there have been inconsistent results. We aimed to investigate whether the association between parental history of dementia and the risk of dementia are different by dementia subtypes and sex of parent and offspring. METHODS: For this cross-sectional study, we harmonized and pooled data for 17,194 older adults from nine population-based cohorts of eight countries. These studies conducted face-to-face diagnostic interviews, physical and neurological examinations, and neuropsychological assessments to diagnose dementia. We investigated the associations of maternal and paternal history of dementia with the risk of dementia and its subtypes in offspring. RESULTS: The mean age of the participants was 72.8 ± 7.9 years and 59.2% were female. Parental history of dementia was associated with higher risk of dementia (odds ratio [OR] = 1.47, 95% confidence interval [CI] = 1.15-1.86) and Alzheimer's disease (AD) (OR = 1.72, 95% CI = 1.31-2.26), but not with the risk of non-AD. This was largely driven by maternal history of dementia, which was associated with the risk of dementia (OR = 1.51, 95% CI = 1.15-1.97) and AD (OR = 1.80, 95% CI = 1.33-2.43) whereas paternal history of dementia was not. These results remained significant when males and females were analyzed separately (OR = 2.14, 95% CI = 1.28-3.55 in males; OR = 1.68, 95% CI = 1.16-2.44 for females). CONCLUSIONS: Maternal history of dementia was associated with the risk of dementia and AD in both males and females. Maternal history of dementia may be a useful marker for identifying individuals at higher risk of AD and stratifying the risk for AD in clinical trials.

Accuracy of automated pure-tone audiometry in population-based samples of older adults.

OBJECTIVE: Automated pure-tone audiometry is frequently used in teleaudiology and hearing screening. Given the high prevalence of age-related hearing loss, older adults are an important target population. This study aimed to investigate the accuracy of automated audiometry in older adults, and to examine the influence of test frequency, age, sex, hearing and cognitive status. DESIGN AND STUDY SAMPLE: In a population-based study, two age-homogeneous samples of 70-year-olds (n = 238) and 85-year-olds (n = 114) were tested with automated audiometry in an office using circum-aural headphones and, around 4 weeks later, with manual audiometry conducted to clinical standards. The differences were analysed for individual frequencies (range: 0.25-8 kHz) and pure-tone averages. RESULTS: The mean difference varied across test frequencies and age groups, the overall figure being -0.7 dB (SD = 8.8, p < 0.001), and 68% to 94% of automated thresholds corresponded within ±10 dB of manual thresholds. The poorest accuracy was found at 8 kHz. Age, sex, hearing and cognitive status were not associated with the accuracy (ordinal regression analysis). CONCLUSIONS: Automated audiometry seems to produce accurate assessments of hearing sensitivity in the majority of older adults, but with larger error margins than in younger populations, and is not affected by relevant patient factors associated with old age.

Associations between dietary patterns and dementia-related neuroimaging markers.

BACKGROUND: The exploration of associations between dietary patterns and dementia-related neuroimaging markers can provide insights on food combinations that may impact brain integrity. METHODS: Data were derived from the Swedish Gothenburg H70 Birth Cohort Study (n = 610). Three dietary patterns were obtained using principal component analysis. Magnetic resonance imaging markers included cortical thickness, an Alzheimer's disease (AD) signature score, small vessel disease, and white matter microstructural integrity. Adjusted linear/ordinal regression analyses were performed. RESULTS: A high-protein and alcohol dietary pattern was negatively associated with cortical thickness in the whole brain (Beta: -0.011; 95% confidence interval [CI]: -0.018 to -0.003), and with an Alzheimer's disease cortical thickness signature score (Beta: -0.013; 95% CI: -0.024 to -0.001). A positive association was found between a Mediterranean-like dietary pattern and white matter microstructural integrity (Beta: 0.078; 95% CI: 0.002-0.154). No associations were found with a Western-like dietary pattern. DISCUSSION: Dietary patterns may impact brain integrity through neurodegenerative and vascular pathways. HIGHLIGHTS: Certain dietary patterns were associated with dementia-related neuroimaging markers. A Mediterranean dietary pattern was positively associated with white matter microstructure. A high-protein and alcohol pattern was negatively associated with cortical thickness.

Sex differences in dementia risk and risk factors: Individual-participant data analysis using 21 cohorts across six continents from the COSMIC consortium.

INTRODUCTION: Sex differences in dementia risk, and risk factor (RF) associations with dementia, remain uncertain across diverse ethno-regional groups. METHODS: A total of 29,850 participants (58% women) from 21 cohorts across six continents were included in an individual participant data meta-analysis. Sex-specific hazard ratios (HRs), and women-to-men ratio of hazard ratios (RHRs) for associations between RFs and all-cause dementia were derived from mixed-effect Cox models. RESULTS: Incident dementia occurred in 2089 (66% women) participants over 4.6 years (median). Women had higher dementia risk (HR, 1.12 [1.02, 1.23]) than men, particularly in low- and lower-middle-income economies. Associations between longer education and former alcohol use with dementia risk (RHR, 1.01 [1.00, 1.03] per year, and 0.55 [0.38, 0.79], respectively) were stronger for men than women; otherwise, there were no discernible sex differences in other RFs. DISCUSSION: Dementia risk was higher in women than men, with possible variations by country-level income settings, but most RFs appear to work similarly in women and men.