Gothenburg H70 Birth Cohort Studies Research Articles

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.

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

BackgroundKeratoconus (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.MethodsA 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.ResultsStatistically 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.ConclusionGenetic variations in the FOXO1 and BANP-ZNF469 genes may be involved in the pathogenesis of sporadic KC.

User experience and biomarker associations of remotely administered and unsupervised smartphone‐based cognitive testing in a community sample of older adults

AbstractBackgroundRemotely administered, unsupervised smartphone‐based cognitive tests have the potential for scalable and cost‐effective screening of Alzheimer’s disease (AD) in clinical trials and primary care. Previous work has provided initial evidence for the feasibility and validity of these tools in clinical and community settings. However, more studies investigating the utility of these cognitive tests are warranted, particularly regarding user experience and the association with AD biomarkers.MethodTo date, 198 participants (CDR 0 = 85%, CDR 0.5 = 15%, Mini‐Mental State Examination = 29, average age = 77) have enrolled in this smartphone sub‐study, a part of the Swedish population‐based Gothenburg H70 Birth Cohort Studies. After participating for at least 12 months, the user experience of smartphone‐based cognitive tests (two memory tests, MDT‐OS and ORR‐LDR) was assessed. Furthermore, we investigated their associations with volumetric brain changes based on magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) biomarkers (Aβ42/Aβ40 ratio, T‐tau, P‐tau, NFL, and neurogranin). The latter will be analyzed in a subsample (n = 45 for CSF and n = 110 for MRI) of all participants. Voxel‐based analyses are being performed in SPM12.ResultMost study participants found the app easy and enjoyable to use, the instructions easy to understand, and they generally favored performing tests in their home environment. Low CSF Aβ42/Aβ40 ratio at age 70 was associated with worse performance on the ORR‐LDR at age 77 (R = .43, p<.002), while measures of t‐tau, p‐tau, NFL, and neurogranin at age 70 were not. Voxel‐wise associations between smartphone‐based cognitive tests and MRI measures will be reported at the conference.ConclusionOur results suggest that using smartphone‐based cognitive tests in a remote unsupervised setting has the potential to identify aspects of early AD in a community‐based setting. The positive user experience is promising for acceptance of these novel tools for cognition assessment. Next steps include analyses of the relation with neuroimaging‐based biomarkers.

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

BackgroundThis study examined how living alone and loneliness associate with all-cause mortality in older men and women.MethodsBaseline 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.ResultsAt 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).ConclusionsLiving 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.

Associations between dietary patterns and structural neuroimaging markers of relevance for dementia

AbstractBackgroundDiet is a lifestyle factors that could influence the risk of developing dementia. However, the impact of diet on the brain is not fully understood. Investigating associations between dietary patterns and neuroimaging markers of relevance for dementia could potentially increase this understanding.MethodThis study includes cross‐sectional data from the population‐based Gothenburg H70 Birth Cohort Studies, Sweden, including 610 dementia‐free 70‐year‐olds (born 1944, examined 2014‐16) with dietary and magnetic resonance imaging (MRI) data (54% women). Three dietary patterns were derived with principal component analysis, a western‐like pattern (e.g., refined cereal products, sweets, savory bakery/fast food), a Mediterranean‐like pattern (e.g., vegetables, fruits, whole grain cereal products) and a low‐fiber and high‐alcohol pattern (e.g., red meat/processed red meat, eggs, alcoholic beverages). Brain MRI markers were of overall neurodegeneration (i.e., mean cortical thickness), Alzheimer’s disease (AD) neurodegeneration (based on cortical thickness of AD‐signature areas), and vascular brain pathology including early abnormalities in the white matter microstructure (derived from diffusion tensor imaging) and small vessel disease (presence of white matter hyperintensities, lacunes, cerebral microbleeds, and/or perivascular spaces). In data analysis, linear and ordinal regression models were adjusted for sex, energy intake, educational level, physical activity level, smoking and body mass index.ResultResults from this study showed a positive association between higher adherence to the Mediterranean‐like dietary pattern and higher white matter microstructural integrity (B 0.077; 95% CI 0.002 – 0.153). Moreover, a higher adherence to the low‐fibre and high‐alcohol dietary pattern was negatively associated with total mean cortical thickness (B ‐0.011; 95% CI ‐0.019 – ‐0.003) and an AD signature of cortical thickness (mean entorhinal, inferior temporal, middle temporal, and fusiform thickness) (B ‐0.013; 95% CI ‐0.024 – ‐0.001) in the fully adjusted models. No associations were found between the dietary patterns and the small vessel disease markers. Nor were there any associations between the western‐like dietary pattern and the MRI markers.ConclusionThis study suggests that there may be an association between certain dietary patterns and dementia‐related alterations. These findings could be of importance for dementia prevention strategies and for future intervention studies investigating the effect of dietary patterns in relation to dementia.

Associations between cerebrospinal fluid biomarkers and brain regions of relevance for very early Alzheimer’s disease processes

AbstractBackgroundThe relation between cerebrospinal fluid (CSF) biomarkers of Alzheimer’s disease (AD) and neurodegeneration and brain regions of relevance for very early pathological processes in AD is poorly understood. This study aims to investigate cross‐sectional associations between the CSF biomarkers amyloid‐β1‐42 (Aβ42), total‐tau (T‐tau), phosphorylated‐tau (P‐tau), neurogranin (Ng) and neurofilament light (NfL) protein and normalized intracranial volumes of the hippocampus, amygdala, entorhinal cortex and basal forebrain observed on structural magnetic resonance imaging (MRI) in cognitively healthy 70‐year olds from the general population.MethodThe analyses included 226 cognitively normal individuals (clinical dementia rating of zero), examined during 2014‐2016 as part of the population‐based Gothenburg H70 Birth Cohort Studies in Sweden. The study participants had undergone lumbar puncture examination to extract CSF samples for biomarker measurements (pg/mL), MRI scan (volumes in mm³), and apolipoprotein E (APOE) genotyping. Linear regressions, adjusted for sex, were used to examine potential associations.ResultElevated CSF T‐tau, P‐tau, and Ng concentrations were associated with smaller volumes of the hippocampus, amygdala, and entorhinal cortex among individuals with amyloid pathology (p = 8×10−8 – 0.04) and among APOE ε4 carriers (p = 8×10−5 – 0.04). In addition, elevated CSF T‐tau, P‐tau, and Ng concentrations were associated with larger basal forebrain among individuals without pathological Aβ42 (p = 0.001 – 0.01) and among APOE ε4 non‐carriers (p = 0.004 – 0.02).ConclusionThe results of our study suggest that among cognitively normal adults who have amyloid pathology or genetic susceptibility to AD, there are associations between axonal degeneration, tangle pathology, and synapse loss and decreased volumes of AD vulnerable brain regions. The associations between elevated CSF biomarkers and larger basal forebrain in cognitively normal individuals were unexpected, but could possibly be explained by compensatory mechanisms or an inflammatory response (generating neuronal or glial swelling) as a very early reaction to the presence of increased levels of tau and Ng. Our findings highlight the clinical pathophysiological relevance of CSF biomarkers of AD and neurodegeneration and how they relate to AD specific brain regions seen on structural MRI in 70‐year‐olds that may be at risk to develop dementia.

Pathophysiological and Clinical Aspects of Hearing Loss Among 85-Year-Olds.

This study aimed to identify the prevalence of conductive/mixed and sensorineural hearing loss, with an attempt to differentiate between sensory and neural components in 85-year-olds. A comprehensive auditory test protocol, including pure-tone audiometry, speech audiometry, auditory brainstem response (ABR), and distortion product otoacoustic emission (DPOAE), was used to identify different types of hearing loss in 85-year-olds. This study comprised a subsample (n = 125) selected from an unscreened cohort of 85-year-olds born in 1930, within the Gothenburg H70 Birth Cohort Studies in Sweden. Test results were reported descriptively. Sensorineural hearing loss was present in one or both ears in almost all participants (98%), and the majority had absent DPOAEs. Only approximately 6% had additional conductive hearing loss, that is, mixed hearing loss. Approximately 20% of the participants with a pure-tone average at 0.5-4 kHz < 60 dB HL had worse word recognition scores compared with predicted scores by the Speech Intelligibility Index (SII), whereas only two participants were classified with neural dysfunction with the use of ABR. Sensorineural hearing loss, likely related to outer hair cell loss, was present in the vast majority of 85-year-olds. Conductive/mixed hearing loss appears to be relatively rare in advanced age. Poor word recognition scores in relation to SII-predicted scores were relatively common (20%) in 85-year-olds, whereas auditory neuropathy was only rarely identified (1.6%) by the use of ABR latencies. To explain abnormal word recognition and to identify the neural component of hearing loss among the older-old population, future research should consider factors such as listening effort and cognition among the older-old population.

Attrition in the Gothenburg H70 birth cohort studies, an 18-year follow-up of the 1930 cohort.

Longitudinal studies are essential to understand the ageing process, and risk factors and consequences for disorders, but attrition may cause selection bias and impact generalizability. We describe the 1930 cohort of the Gothenburg H70 Birth Cohort Studies, followed from age 70 to 88, and compare baseline characteristics for those who continue participation with those who die, refuse, and drop out for any reason during follow-up. A population-based sample born 1930 was examined with comprehensive assessments at age 70 (N = 524). The sample was followed up and extended to increase sample size at age 75 (N = 767). Subsequent follow-ups were conducted at ages 79, 85, and 88. Logistic regression was used to analyze baseline characteristics in relation to participation status at follow-up. Refusal to participate in subsequent examinations was related to lower educational level, higher blood pressure, and lower scores on cognitive tests. Both attrition due to death and total attrition were associated with male sex, lower educational level, smoking, ADL dependency, several diseases, poorer lung function, slower gait speed, lower scores on cognitive tests, depressive symptoms, and a larger number of medications. Attrition due to death was also associated with not having a partner. It is important to consider different types of attrition when interpreting results from longitudinal studies, as representativeness and results may be differently affected by different types of attrition. Besides reducing barriers to participation, methods such as imputation and weighted analyses can be used to handle selection bias.

Cerebrospinal fluid biomarkers of axonal and synaptic degeneration in a population-based sample

BackgroundNeurofilament light (NfL) and neurogranin (Ng) are promising candidate AD biomarkers, reflecting axonal and synaptic damage, respectively. Since there is a need to understand the synaptic and axonal damage in preclinical Alzheimer’s disease (AD), we aimed to determine the cerebrospinal fluid (CSF) levels of NfL and Ng in cognitively unimpaired elderly from the Gothenburg H70 Birth Cohort Studies classified according to the amyloid/tau/neurodegeneration (A/T/N) system.MethodsThe sample consisted of 258 cognitively unimpaired older adults (age 70, 129 women and 129 men) from the Gothenburg Birth Cohort Studies. We compared CSF NfL and Ng concentrations in A/T/N groups using Student’s T-test and ANCOVA.ResultsCSF NfL concentration was higher in the A−T−N+ group (p=0.001) and the A−T+N+ group (p=0.006) compared with A−T−N−. CSF Ng concentration was higher in the A−T−N+, A−T+N+, A+T−N+, and A+T+N+ groups (p<0.0001) compared with A−T−N−. We found no difference in NfL or Ng concentration in A+ compared with A− (disregarding T− and N− status), whereas those with N+ had higher concentrations of NfL and Ng compared with N− (p<0.0001) (disregarding A− and T− status).ConclusionsCSF NfL and Ng concentrations are increased in cognitively normal older adults with biomarker evidence of tau pathology and neurodegeneration.

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

Little is known about alcohol consumption among the oldest old. To compare alcohol use and drinking patterns among 85 year olds born three decades apart. Cross-sectional. The Gothenburg H70 Birth Cohort Studies. About 1,160 85 year olds born in 1901-02, 1923-24, and 1930. 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 ≥100g 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. 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. 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.

Decreasing Incidence and Prevalence of Dementia Among Octogenarians: APopulation-Based Study on 3 Cohorts Born 30 Years Apart.

Recent studies suggest a decline in the age-specific incidence and prevalence of dementia. However, results are mixed regarding trends among octogenarians. We investigated time trends in the prevalence and incidence of dementia in 3 population-based cohorts of 85-90-year olds. We also examined if there were different time trends for men and women. We examined population-based birth cohorts within the Gothenburg H70 Birth Cohort Studies born 1901-02, 1923-24, and 1930, at ages 85 (N=1481) and 88 (N=840) years. The first 2 cohorts were also examined at age 90 (N=450). The incidence was examined in 1109 individuals free from dementia at baseline using information from the examination at age 88 or register data. All 3 cohorts were examined with identical methods. The prevalence of dementia decreased from 29.8% in 1986-87 to 21.5% in 2008-10 and 24.5% in 2015-16 among 85-year olds, and from 41.9% in 1989-90 to 28.0% in 2011-12 to 21.7% in 2018-19 among 88-year olds, and from 41.5% in 1991-92 to 37.2% in 2013-14 among 90-year olds. The decline was most accentuated among women. The incidence of dementia per 1000 risk-years from ages 85 to 89 declined from 48.8 among those born 1901-02 to 37.9 in those born 1923-24 to 22.5 among those born 1930. The prevalence and incidence of dementia decreased substantially over 3 decades among octogenarians. This might slow down the projected increase in cases of dementia expected by the increasing number of octogenarians during the following decades.

Subtle Differences in Cognition in 70-Year-Olds with Elevated Cerebrospinal Fluid Neurofilament Light and Neurogranin: A H70 Cross-Sectional Study.

Most research on cerebrospinal fluid (CSF) neurofilament light protein (NfL) as a marker for neurodegeneration and neurogranin (Ng) for synaptic dysfunction has largely focused on clinical cohorts rather than population-based samples. We hypothesized that increased CSF levels of NfL and Ng are associated with subtle cognitive deficits in cognitively unimpaired (CU) older adults. The sample was derived from the Gothenburg H70 Birth Cohort Studies and comprised 258 CU 70-year-olds, with a Clinical Dementia Rating score of zero. All participants underwent extensive cognitive testing. CSF levels of NfL and Ng, as well as amyloid β1-42, total tau, and phosphorylated tau, were measured. Participants with high CSF NfL performed worse in one memory-based test (Immediate recall, p = 0.013) and a language test (FAS, p = 0.016). Individuals with high CSF Ng performed worse on the memory-based test Supra Span (p = 0.035). When stratified according to CSF tau and Aβ42 concentrations, participants with high NfL and increased tau performed worse on a memory test than participants normal tau concentrations (Delayed recall, p = 0.003). In participants with high NfL, those with pathologic Aβ42 concentrations performed worse on the Delayed recall memory (p = 0.044). In the high Ng group, participants with pathological Aβ42 concentrations had lower MMSE scores (p = 0.027). However, in regression analysis we found no linear correlations between CSF NfL or CSF Ng in relation to cognitive tests when controlled for important co-variates. Markers of neurodegeneration and synaptic pathology might be associated with subtle signs of cognitive decline in a population-based sample of 70-year-olds.

Smartphone-based long-term delayed memory performance is associated with the Preclinical Alzheimer's Cognitive Composite and CSF levels of β-amyloid.

Remote and unsupervised cognitive testing using smartphones may improve sensitivity to detect preclinical Alzheimer's disease (AD). In particular, cognitive testing at-home enables the evaluation of the potentially more sensitive long-term delayed memory retrieval, which is commonly not feasible in a clinical setting. Here, we investigated the association between remote and unsupervised smartphone-based cognitive assessments and in-clinic cognitive measurement in older participants (CDR = 0, MMSE = 29.2, age = 77). The sample (non-demented at age 70) was derived from the Swedish population-based Gothenburg H70 Birth Cohort Studies. In a subsample of participants, the retrospective correlation with cerebrospinal fluid (CSF) biomarkers analyzed at age 70 was further explored. To this point, 177 H70-participants have consented and were enrolled into the smartphone sub-study. They completed an "Object-in-Room Recall Test" (ORR) remotely and unsupervised using own mobile devices, and the recall session was initiated 24 hours after the initial learning phase. Available previously assessed CSF measures included the Aβ42/Aβ40-ratio, t-tau, p-tau, neurofilament light (NFL), and neurogranin, available in-clinic cognitive tests included the Rey Auditory Verbal Learning Test (RAVLT), Semantic Fluency, Digit-Symbol-Coding, and Mini Mental State Examination. The above-mentioned cognitive tests were used to derive the Preclinical Alzheimer's Cognitive Composite (PACC5), a composite designed to be sensitive to cognitive change in preclinical AD. All associations were examined using Pearson correlation coefficient. Preliminary analyses in a subset of participants yielded relatively strong positive correlations between PACC5 (R = .50, p<.001) and the ORR Long-term Delayed Retrieval. The strongest correlation for an individual test was observed between the RAVLT Delayed Retrieval and the ORR Long-term Delayed Retrieval (R = .52, p<.001). Regarding the CSF biomarkers, Aβ42/Aβ40-ratio at age 70 was positively correlated with the ORR Long-term Delayed Retrieval at age 77 (R = .43, p<.01), while measures of t-tau, p-tau, NFL, and neurogranin at age 70 were not. Our findings demonstrate the potential of smartphone-based cognitive assessment to detect features of preclinical AD in a population-based sample of older adults. Future analyses will address the relationship between these novel cognitive measures in relation to longitudinal CSF- and neuroimaging-based biomarkers and clinical progression.

Smartphone‐based long‐term delayed memory performance is associated with the Preclinical Alzheimer’s Cognitive Composite and CSF levels of β‐amyloid

AbstractBackgroundRemote and unsupervised cognitive testing using smartphones may improve sensitivity to detect preclinical Alzheimer’s disease (AD). In particular, cognitive testing at‐home enables the evaluation of the potentially more sensitive long‐term delayed memory retrieval, which is commonly not feasible in a clinical setting.MethodHere, we investigated the association between remote and unsupervised smartphone‐based cognitive assessments and in‐clinic cognitive measurement in older participants (CDR = 0, MMSE = 29.2, age = 77). The sample (non‐demented at age 70) was derived from the Swedish population‐based Gothenburg H70 Birth Cohort Studies. In a subsample of participants, the retrospective correlation with cerebrospinal fluid (CSF) biomarkers analyzed at age 70 was further explored. To this point, 177 H70‐participants have consented and were enrolled into the smartphone sub‐study. They completed an “Object‐in‐Room Recall Test“ (ORR) remotely and unsupervised using own mobile devices, and the recall session was initiated 24 hours after the initial learning phase. Available previously assessed CSF measures included the Aβ42/Aβ40‐ratio, t‐tau, p‐tau, neurofilament light (NFL), and neurogranin, available in‐clinic cognitive tests included the Rey Auditory Verbal Learning Test (RAVLT), Semantic Fluency, Digit‐Symbol‐Coding, and Mini Mental State Examination. The above‐mentioned cognitive tests were used to derive the Preclinical Alzheimer’s Cognitive Composite (PACC5), a composite designed to be sensitive to cognitive change in preclinical AD. All associations were examined using Pearson correlation coefficient.ResultPreliminary analyses in a subset of participants yielded relatively strong positive correlations between PACC5 (R = .50, p&lt;.001) and the ORR Long‐term Delayed Retrieval. The strongest correlation for an individual test was observed between the RAVLT Delayed Retrieval and the ORR Long‐term Delayed Retrieval (R = .52, p&lt;.001). Regarding the CSF biomarkers, Aβ42/Aβ40‐ratio at age 70 was positively correlated with the ORR Long‐term Delayed Retrieval at age 77 (R = .43, p&lt;.01), while measures of t‐tau, p‐tau, NFL, and neurogranin at age 70 were not.ConclusionOur findings demonstrate the potential of smartphone‐based cognitive assessment to detect features of preclinical AD in a population‐based sample of older adults. Future analyses will address the relationship between these novel cognitive measures in relation to longitudinal CSF‐ and neuroimaging‐based biomarkers and clinical progression.

THE NEW AGING: HOW DIFFERENT ASPECTS OF AGING HAVE CHANGED OVER HALF A CENTURY. THE H70 STUDIES WITHIN NEAR

Abstract The number and proportions of older people are increasing world-wide. The Gothenburg H70 Birth Cohort Studies started in 1971 and are still on-going. The studies include representative birth cohorts born 1901-02, 1906-07, 1911-12, 1922, 1923-24, 1930, and 1944 followed longitudinally from age 70 until death. The studies include psychiatric, somatic, audiological, opthalmological, psychological, social, genetic, dietary, functional, and psychometric examinations, personality, collection of blood, plasma, serum, and cerebrospinal fluid, and examinations with MRI. During the study period, cognitive and physical functions, and hearing, has improved considerably, the prevalence and incidence of dementia has decreased, the prevalence of depression and psychotic disorders has decreased, and sexual activity and alcohol consumption has increased considerably. Even personality has changed. Present older people are less neurotic and more extrovert. Our study shows that aging is a changing concept, and that previous knowledge needs to be continuously updated, as new generations reach old age.

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

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. Prospective cohort study. Population-based samples of older adults in Gothenburg, Sweden. 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). 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. 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). 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.

High polygenic risk score for exceptional longevity is associated with a healthy metabolic profile

Healthy metabolic measures in humans are associated with longevity. Dysregulation leads to metabolic syndrome (MetS) and negative health outcomes. Recent exceptional longevity (EL) genome wide association studies have facilitated estimation of an individual’s polygenic risk score (PRS) for EL. We tested the hypothesis that individuals with high ELPRS have a low prevalence of MetS. Participants were from five cohorts of middle-aged to older adults. The primary analyses were performed in the UK Biobank (UKBB) (n = 407,800, 40–69 years). Replication analyses were undertaken using three Australian studies: Hunter Community Study (n = 2122, 55–85 years), Older Australian Twins Study (n = 539, 65–90 years) and Sydney Memory and Ageing Study (n = 925, 70–90 years), as well as the Swedish Gothenburg H70 Birth Cohort Studies (n = 2273, 70–93 years). MetS was defined using established criteria. Regressions and meta-analyses were performed with the ELPRS and MetS and its components. Generally, MetS prevalence (22–30%) was higher in the older cohorts. In the UKBB, high EL polygenic risk was associated with lower MetS prevalence (OR = 0.94, p = 1.84 × 10–42) and its components (p < 2.30 × 10–8). Meta-analyses of the replication cohorts showed nominal associations with MetS (p = 0.028) and 3 MetS components (p < 0.05). This work suggests individuals with a high polygenic risk for EL have a healthy metabolic profile promoting longevity.

Slowing gait speed precedes cognitive decline by several years.

IntroductionIn this longitudinal study, we aimed to examine if slowing gait speed preceded cognitive decline and correlated with brain amyloidosis.MethodsThe sample (n = 287) was derived from the Gothenburg H70 Birth Cohort Studies, with follow‐ups between 2000 and 2015. Gait speed was measured by indoor walk, and cognition using the Clinical Dementia Rating (CDR) score. All participants had CDR = 0 at baseline. Some participants had data on cerebrospinal fluid (CSF) amyloid beta (Aβ)1‐42 concentrations at the 2009 examination.ResultsGait speed for participants who worsened in CDR score during follow‐up was slower at most examinations. Baseline gait speed could significantly predict CDR change from baseline to follow‐up. Subjects with pathological CSF Aβ1‐ 42 concentrations at the 2009 visit had lost more gait speed compared to previous examinations.DiscussionOur results indicate that gait speed decline precedes cognitive decline, is linked to Alzheimer's pathology, and might be used for early detection of increased risk for dementia development.

Interactions between dietary patterns and genetic factors in relation to incident dementia among 70‐year‐olds

AbstractBackgroundGenetic and lifestyle factors influence the risk of developing dementia. Diet is one of the modifiable lifestyle factors thought to affect risk, but it is unclear whether there is an interplay with genetic risk factors in relation to incident dementia.MethodData was derived from the population‐based Gothenburg H70 Birth Cohort Studies based in Sweden, including 602 dementia‐free 70‐year‐olds (born 1922 or 1930; 64% women) with dietary and genetic data followed for incident dementia until 2016. Two dietary patterns were derived with reduced rank regression analysis, one healthy (e.g., fruits, vegetables, fish) and one western (e.g., full‐fat dairy products, refined bread, red and processed meat). Genetic risk was determined by APOE ε4 status and four non‐APOE AD‐polygenic risk scores (AD‐PRSs). Gene‐diet interactions in relation to incident dementia were analysed with cox regression models. If an interaction at a p‐value threshold of p&lt; 0.20 was detected, stratified analyses were performed. Analyses were adjusted for sex, energy intake, birth year, age at examination, educational level, physical activity level, cardiovascular risk factors and 10 principal components (to correct for population stratification).ResultThere was an interaction between APOE ε4 status and a healthy and a western dietary pattern in relation to incident dementia (p=0.13 and p=0.07), while no interactions were found between AD‐PRSs and dietary patterns. Those with higher adherence to a healthy dietary pattern had a reduced risk of dementia (HR 0.77; 95% CI 0.64–0.94, p=0.008) among ε4 non‐carriers, but not among ε4 carriers. There was a borderline association between a western dietary pattern and an increased risk of dementia among ε4 carriers (HR 1.25; 95% CI 0.97–1.61, p=0.08), while no association was observed among ε4 non‐carriers.ConclusionThe results suggest an interplay between APOE ε4 status and adherence to dietary patterns in relation to incident dementia. The findings from this study could be of importance for dementia prevention strategies and for future intervention studies investigating the effect of dietary patterns in relation to dementia incidence.

Relative Validity of a Short 15-Item Food Frequency Questionnaire Measuring Dietary Quality, by the Diet History Method.

Food frequency questionnaires (FFQ) are commonly used dietary assessment tools. The aim was to assess the relative validity of a 15-item FFQ, designed for the screening of poor dietary patterns with a validated diet history (DH). The study population was derived from the Gothenburg H70 Birth Cohort Studies. The DH registrations were harmonized in accordance with the FFQ frequencies. The agreement was assessed by Cohen’s kappa with corresponding confidence intervals (CI) for the frequency and categorical variables. Bland–Altman plots were used for the numeric variables. The study comprised data from 848 individuals (55.2% women). Overall, there was high agreement between the methods, with the exact and adjacent level of agreement over 80% for eight variables. The proportion attributed to the opposite frequency was fairly low for most of the frequency variables. Most of the kappa values were in fair or moderate agreement. The highest kappa values were calculated for the type of cooking fat (k = 0.68, CI = 0.63–0.72) and sandwich spread (k = 0.55, CI = 0.49–0.53), and the lowest for type of bread (0.13, CI = 0.07–0.20) and sweets (0.22 CI = 0.18–0.27). In conclusion, the FFQ showed overall good agreement compared with the DH. We, therefore, think it, with some improvements, could serve as a simple screening tool for poor dietary patterns.