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.

Accuracy of 12 short versions of the Geriatric Depression Scale to detect depression in a prospective study of a high-risk population with different levels of cognition.

OBJECTIVES: To determine the accuracy of 12 previously validated short versions of the Geriatric Depression Scale (GDS) to detect major depressive disorder (MDD) in a high-risk population with and without global cognitive impairment. DESIGN: Cross-sectional study. SETTING: Five hospitals, Western Sweden. PARTICIPANTS: Older adults (age ≥70 years, n = 60) assessed at a home visit 1 year after hospital care in connection with suicide attempt. MEASUREMENTS: Depression symptoms were rated using the established 15-item GDS. Eleven short GDS versions identified by a recent systematic review were derived from this administered version. Receiver operating characteristic curves and area under the curve (AUC) for the identification of MDD diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, were obtained for each version. The Youden Index optimal criterion was used to determine the appropriate cutoffs. Analyses were repeated after stratification by cognitive status (Mini Mental State Examination score ≤24 and >24) for the best performing GDS short versions and the established 15-item GDS. RESULTS: The 7-item GDS according to Broekman et al. (), with a cutoff 3, was the most accurate among the 12 short versions (AUC 0.90, 95% confidence interval 0.80-1.00), identifying MDD with sensitivity 88% and specificity 81%. The cutoff score remained consistent in the presence of global cognitive impairment, which was not the case for the standardized 15-item GDS. CONCLUSION: The Broekman 7-item GDS had high accuracy to detect MDD in this prospective clinical cohort at high risk for MDD. Further testing of GDS short versions in diverse settings is required.

Slowing gait speed precedes cognitive decline by several years.

INTRODUCTION: In this longitudinal study, we aimed to examine if slowing gait speed preceded cognitive decline and correlated with brain amyloidosis. METHODS: The 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 (Aß)1-42 concentrations at the 2009 examination. RESULTS: Gait 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 Aß1- 42 concentrations at the 2009 visit had lost more gait speed compared to previous examinations. DISCUSSION: Our 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.

Dementia remains the major predictor of death among octogenarians. A study of two population cohorts of 85-year-olds examined 22 years apart.

Dementia is the major predictor of death in old age. The aim of this paper was to determine whether 8-year mortality among 85-year olds with and without dementia, and if the contribution of dementia to mortality relative to other common diseases has changed. We used two population-based cohorts of 85-year-olds (N = 1065), born in 1901-02 and 1923-24, which were examined with identical methods in 1986-87 and 2008-2010 and followed for 8-year mortality according to data from the Swedish Tax Agency. Dementia was diagnosed according to DSM-III-R. Other diseases were diagnosed based on self-reports, close informant interviews, somatic examinations, and the Swedish National In-patient Register. Compared to cohort 1901-02, cohort 1923-24 had a lower 8-year mortality both among those with (HR 0.7; 95% CI 0.5-0.99) and without dementia (HR 0.7; 95% CI 0.5-0.9). Dementia was associated with increased mortality in both cohorts (cohort 1901-02, HR 2.6; 95% CI 2.0-3.2, cohort 1923-24, HR 2.8; 95% CI 2.3-3.5), and remained the major predictor of death, with a population attributable risk of 31.7% in 1986-87 and 27.7% in 2008-10. Dementia remained the most important predictor of death in both cohorts. The relative risk for mortality with dementia did not change between cohorts, despite a decreased mortality rate in the population.

The Gothenburg H70 Birth cohort study 2014-16: design, methods and study population.

To improve health care for older persons, we need to learn more about ageing, e.g. identify protective factors and early markers for diseases. The Gothenburg H70 Birth Cohort Studies (the H70 studies) are multidisciplinary epidemiological studies examining representative birth cohorts of older populations in Gothenburg, Sweden. So far, six birth cohorts of 70-year-olds have been examined over time, and examinations have been virtually identical between studies. This paper describes the study procedures for the baseline examination of the Birth cohort 1944, conducted in 2014-16. In this study, all men and women born 1944 on specific dates, and registered as residents in Gothenburg, were eligible for participation (n = 1839). A total of 1203 (response rate 72.2%; 559 men and 644 women; mean age 70.5 years) agreed to participate in the study. The study comprised sampling of blood and cerebrospinal fluid, psychiatric, cognitive, and physical health examinations, examinations of genetics and family history, use of medications, social factors, functional ability and disability, physical fitness and activity, body composition, lung function, audiological and ophthalmological examinations, diet, brain imaging, as well as a close informant interview, and qualitative studies. As in previous examinations, data collection serves as a basis for future longitudinal follow-up examinations. The research gained from the H70 studies has clinical relevance in relation to prevention, early diagnosis, clinical course, experience of illness, understanding pathogenesis and prognosis. Results will increase our understanding of ageing and inform service development, which may lead to enhanced quality of care for older persons.

Chronic depressive symptomatology and CSF amyloid beta and tau levels in mild cognitive impairment.

OBJECTIVES: To investigate the association between chronic subsyndromal symptoms of depression (SSD), cerebrospinal fluid (CSF) biomarkers, and neuropsychological performance in individuals with mild cognitive impairment (MCI). METHODS: Participants included 238 older adults diagnosed with MCI from the Alzheimer's Disease Neuroimaging Initiative repository with cognitive and CSF amyloid beta (Aß1-42 ), total tau (t-tau), and phosphorylated tau (p-tau) data. The Neuropsychiatric Inventory identified individuals with chronic endorsement (SSD group N = 80) or no endorsement (non-SSD group N = 158) of depressive symptoms across timepoints. CSF biomarker and cognitive performance were evaluated with linear regression models adjusting for age, education, gender, APOE genotype, global cognitive status, and SSD group. RESULTS: As compared to the non-SSD group, the SSD group displayed lower CSF Aß1-42 levels (ß = -24.293, S.E. = 6.345, P < 0.001). No group differences were observed for CSF t-tau (P = 0.497) or p-tau levels (P = 0.392). Lower CSF Aß1-42 levels were associated with poorer performance on learning (ß = 0.041, S.E. = 0.018, P = 0.021) and memory (ß = -0.012, S.E. = 0.005, P = 0.031) measures, whereas higher CSF t-tau levels were associated with poorer performance on measures of global cognition (ß = 0.022, S.E = 0.008, P = 0.007) and language (ß = -0.010, S.E = 0.004, P = 0.019). SSD was independently associated with diminished global cognition, learning and memory, language, and executive function performance over and above the effects of CSF biomarkers (all P < 0.05). CONCLUSIONS: MCI participants with SSD displayed diminished CSF Aß1-42 levels but did not differ from non-SSD controls in CSF tau levels. Additionally, CSF biomarkers and SSD independently accounted for variance in cognitive performance, suggesting that these factors may uniquely confer cognitive risk in MCI.

Cortical Atrophy is Associated with Accelerated Cognitive Decline in Mild Cognitive Impairment with Subsyndromal Depression.

OBJECTIVES: To investigate the association between cognitive decline and cortical atrophy in individuals with mild cognitive impairment (MCI) and chronic subsyndromal symptoms of depression (SSD) over a 4-year period. DESIGN: Prospective cohort study. SETTING: Multicenter, clinic-based. PARTICIPANTS: Within the Alzheimer's Disease Neuroimaging Initiative repository, the Neuropsychiatric Inventory was used to identify individuals with MCI and stable endorsement (SSD group N = 32) or no endorsement (non-SSD group N = 69) of depressive symptoms across time points. MEASUREMENTS: Repeated measures of cognitive outcomes, cortical atrophy, and their associations were evaluated with mixed effects models adjusting for age, education, sex, and APOE genotype. RESULTS: The SSD group demonstrated accelerated decline on measures of global cognition (Alzheimer Disease Assessment Scale; df = 421, t = 2.242, p = 0.025), memory (Wechsler Memory Scale-Revised Logical Memory II; df = 244, t = -2.525, p = 0.011), information processing speed (Trail Making Test Parts A [df = 421, t = 2.376, p = 0.018] and B [df = 421, t = 2.533, p = 0.012]), and semantic fluency (Category Fluency; df = 424, t = -2.418, p = 0.016), as well as accelerated frontal lobe (df = 341, t = -2.648, p = 0.008) and anterior cingulate (df = 341, t = -3.786, p < 0.001) atrophy. No group differences were observed for rate of decline on measures of attention, learning, and confrontation naming or for rate of atrophy in any other regions. Accelerated frontal lobe and anterior cingulate atrophy was associated with cognitive decline on measures of global cognition, information processing speed, and semantic fluency (all p < 0.05), but not memory. CONCLUSIONS: Individuals with chronic SSD may represent an MCI subgroup that is highly vulnerable to accelerated cognitive decline, an effect that may be governed by frontal lobe and anterior cingulate atrophy.

Chronic Depressive Symptomatology in Mild Cognitive Impairment Is Associated with Frontal Atrophy Rate which Hastens Conversion to Alzheimer Dementia.

OBJECTIVE: Investigate the association of chronic depressive symptomatology (chrDS) with cortical atrophy rates and conversion to Alzheimer dementia (AD) over 3 years in mild cognitive impairment (MCI). METHODS: In a multicenter, clinic-based study, MCI elderly participants were selected from the Alzheimer's Disease Neuroimaging Initiative repository, based on availability of both serial structural magnetic resonance imaging and chrDS endorsed on three depression-related items from the Neuropsychiatric Inventory Questionnaire (chrDS N = 32 or no depressive symptoms N = 62) throughout follow-up. Clinical and laboratory investigations were performed every 6 months during the first 2 years and yearly thereafter (median follow-up: 3 years; interquartile range: 1.5-4.0 years). Cortical atrophy rates in 16 predefined frontotemporoparietal regions affected in major depression and AD and the rate of incident AD at follow-up. RESULTS: ChrDS in a single domain amnestic MCI sample were associated with accelerated cortical atrophy in the frontal lobe and anterior cingulate but not with atrophy rates in temporomedial or other AD-affected regions. During follow-up, 38 participants (42.7%) developed AD. Participants with chrDS had 60% shorter conversion time to AD than those without depressive symptoms. This association remained significant in survival models adjusted for temporomedial atrophy rates and showed the same trend in models adjusted for frontal cortical atrophy rate, which all increased the risk of AD. CONCLUSION: Our results suggest that chrDS associated with progressive atrophy of frontal regions may represent an additional risk factor for conversion to dementia in MCI as opposite to representing typical prodromal AD symptomatology.

High Prevalence of Stress and Low Prevalence of Alzheimer Disease CSF Biomarkers in a Clinical Sample with Subjective Cognitive Impairment.

BACKGROUND/AIMS: Subjective cognitive impairment (SCI) is a trigger for seeking health care in a possible preclinical phase of Alzheimer's disease (AD), although the characteristics of SCI need clarification. We investigated the prevalence of psychosocial stress, depressive symptoms and CSF AD biomarkers in SCI and MCI (mild cognitive impairment). METHODS: Memory clinic patients (SCI: n = 90; age: 59.8 ± 7.6 years; MCI: n = 160; age: 63.7 ± 7.0 years) included in the Gothenburg MCI study were examined at baseline. Variables were analyzed using logistic regression with SCI as dependent variable. RESULTS: Stress was more prevalent in SCI (51.1%) than MCI (23.1%); p < 0.0005. SCI patients had more previous depressive symptoms (p = 0.006), but showed no difference compared to MCI patients considering current depressive symptoms. A positive CSF AD profile was present in 14.4% of SCI patients and 35.0% of MCI patients (p = 0.001). Stress (p = 0.002), previous stress/depressive symptoms (p = 0.006) and a negative CSF AD profile (p = 0.036) predicted allocation to the SCI group. CONCLUSION: Psychosocial stress is more prevalent in SCI than previously acknowledged. The high prevalence and long-term occurrence of stress/depressive symptoms in SCI in combination with a low prevalence of altered CSF AD biomarkers strengthens the notion that AD is not the most likely etiology of SCI.

Cognitive Function in Older Suicide Attempters and a Population-Based Comparison Group.

OBJECTIVE: The aim was to compare cognitive function in older suicide attempters with a population-based comparison group. METHODS: Hospitalized suicide attempters aged 70 years and older were assessed cognitively at baseline (n = 99) and 1-year follow-up (n = 59). Depression symptoms were rated with the Montgomery-Åsberg Depression Rating Scale (MADRS). Results of cognitive assessments in attempters were compared with results in nonattempter comparison subjects (n = 115) selected among participants in our population-based health studies to yield a similar distribution of MADRS scores. RESULTS: Suicide attempters scored lower on Mini-Mental State Examination (MMSE) than comparison persons. Among attempters, the mean MMSE score was lower in those with medically serious attempts. Attempters displayed poorer performance on tests of pentagon drawing and abstract thinking compared to comparison persons, and the results remained also after exclusion of those with medically serious attempts. At 1-year follow-up, significant improvement in MADRS scores was observed in the attempters. No evidence of improvement could be shown regarding cognitive deficits. CONCLUSION: Older suicide attempters may have cognitive deficits, which may in part be related to the attempt itself. This needs to be taken into account when designing intervention strategies.

Association of CSF biomarkers with MRI brain changes in Alzheimer's disease.

The relation between cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) and magnetic resonance imaging (MRI) measures is poorly understood in cognitively healthy individuals from the general population. Participants' (n = 226) mean age was 70.9 years (SD = 0.4). CSF concentrations of amyloid beta (Aß)1-42, total tau (t-tau), phosphorylated tau (p-tau), neurogranin, and neurofilament light, and volumes of hippocampus, amygdala, total basal forebrain (TBF), and cortical thickness were measured. Linear associations between CSF biomarkers and MRI measures were investigated. In Aß1-42 positives, higher t-tau and p-tau were associated with smaller hippocampus (P = 0.001 and P = 0.003) and amygdala (P = 0.005 and P = 0.01). In Aß1-42 negatives, higher t-tau, p-tau, and neurogranin were associated with larger TBF volume (P = 0.001, P = 0.001, and P = 0.01). No associations were observed between the CSF biomarkers and an AD signature score of cortical thickness. AD-specific biomarkers in cognitively healthy 70-year-olds may be related to TBF, hippocampus, and amygdala. Lack of association with cortical thickness might be due to early stage of disease.

Biomarkers of Alzheimer's Disease and Cerebrovascular Disease in Relation to Depressive Symptomatology in Individuals With Subjective Cognitive Decline.

BACKGROUND: Subjective cognitive decline (SCD) has gained recent interest as a potential harbinger of neurodegenerative diseases such as Alzheimer's disease (AD) and cerebrovascular disease (CVD). In addition, SCD can be related to depressive symptomatology. However, the association between AD and CVD biomarkers, depressive symptomatology, and SCD is still unclear. We investigated the association of AD and CVD biomarkers and depressive symptomatology with SCD in individuals with subjective memory complaints (SCD-memory group) and individuals with subjective concentration complaints (SCD-concentration group). METHODS: We recruited a population-based cohort of 217 individuals (all aged 70 years, 53% female participants, 119 SCD-memory individuals, 23 SCD-concentration individuals, and 89 controls). AD and CVD were assessed through cerebrospinal fluid levels of the Aß42/40 ratio and phosphorylated tau, and white matter signal abnormalities on magnetic resonance imaging, respectively. Associations between biomarkers, depressive symptomatology, and SCD were tested via logistic regression and correlation analyses. RESULTS: We found a significant association between depressive symptomatology with SCD-memory and SCD-concentration. Depressive symptomatology was not associated with AD and CVD biomarkers. Both the phosphorylated tau biomarker and depressive symptomatology predicted SCD-memory, and the Aß42/40 ratio and depressive symptomatology predicted SCD-concentration. CONCLUSIONS: The role of depressive symptomatology in SCD may differ depending on the stage within the spectrum of preclinical AD (as determined by amyloid-beta and tau positivity), and does not seem to reflect AD pathology. Our findings contribute to the emerging field of subclinical depressive symptomatology in SCD and clarify the association of different types of subjective complaints with distinct syndromic and biomarker profiles.

Changes in prevalence and incidence of dementia and risk factors for dementia: an analysis from cohort studies.

BACKGROUND: Some cohort studies have reported a decline in dementia prevalence and incidence over time, although these findings have not been consistent across studies. We reviewed evidence on changes in dementia prevalence and incidence over time using published population-based cohort studies that had used consistent methods with each wave and aimed to quantify associated changes in risk factors over time using population attributable fractions (PAFs). METHODS: We searched for systematic reviews of cohort studies examining changes in dementia prevalence or incidence over time. We searched PubMed for publications from database inception up to Jan 12, 2023, using the search terms "systematic review" AND "dementia" AND ("prevalence" OR "incidence"), with no language restrictions. We repeated this search on March 28, 2024. From eligible systematic reviews, we searched the references and selected peer-reviewed publications about cohort studies where dementia prevalence or incidence was measured in the same geographical location, at a minimum of two timepoints, and that reported age-standardised prevalence or incidence of dementia. Additionally, data had to be from population-based samples, in which participants' cognitive status was assessed and where validated criteria were used to diagnose dementia. We extracted summary-level data from each paper about dementia risk factors, contacting authors when such data were not available in the published paper, and calculated PAFs for each risk factor at all available timepoints. Where possible, we linked changes in dementia prevalence or incidence with changes in the prevalence of risk factors. FINDINGS: We identified 1925 records in our initial search, of which five eligible systematic reviews were identified. Within these systematic reviews, we identified 71 potentially eligible primary papers, of which 27 were included in our analysis. 13 (48%) of 27 primary papers reported change in prevalence of dementia, ten (37%) reported change in incidence of dementia, and four (15%) reported change in both incidence and prevalence of dementia. Studies reporting change in dementia incidence over time in Europe (n=5) and the USA (n=5) consistently reported a declining incidence in dementia. One study from Japan reported an increase in dementia prevalence and incidence and a stable incidence was reported in one study from Nigeria. Overall, across studies, the PAFs for less education or smoking, or both, generally declined over time, whereas PAFs for obesity, hypertension, and diabetes generally increased. The decrease in PAFs for less education and smoking was associated with a decline in the incidence of dementia in the Framingham study (Framingham, MA, USA, 1997-2013), the only study with sufficient data to allow analysis. INTERPRETATION: Our findings suggest that lifestyle interventions such as compulsory education and reducing rates of smoking through country-level policy changes could be associated with an observed reduction, and therefore future reduction, in the incidence of dementia. More studies are needed in low-income and middle-income countries, where the burden of dementia is highest, and continues to increase. FUNDING: National Institute for Health and Care Research Three Schools' Dementia Research Programme.

Longstanding smoking associated with frontal brain lobe atrophy: a 32-year follow-up study in women.

OBJECTIVE: To examine the association between midlife tobacco smoking and late-life brain atrophy and white matter lesions. METHODS: The study includes 369 women from the Prospective Population Study of Women in Gothenburg, Sweden. Cigarette smoking was reported at baseline 1968 (mean age=44 years) and at follow-up in 1974-1975 and 1980-1981. CT of the brain was conducted 32 years after baseline examination (mean age=76 years) to evaluate cortical atrophy and white matter lesions. Multiple logistic regressions estimated associations between midlife smoking and late-life brain lesions. The final analyses were adjusted for alcohol consumption and several other covariates. RESULTS: Smoking in 1968-1969 (adjusted OR 1.85; 95% CI 1.12 to 3.04), in 1974-1975 (OR 2.37; 95% CI 1.39 to 4.04) and in 1980-1981 (OR 2.47; 95% CI 1.41 to 4.33) were associated with late-life frontal lobe atrophy (2000-2001). The strongest association was observed in women who reported smoking at all three midlife examinations (OR 2.63; 95% CI 1.44 to 4.78) and in those with more frequent alcohol consumption (OR 6.02; 95% CI 1.74 to 20.84). Smoking in 1980-1981 was also associated with late-life parietal lobe atrophy (OR 1.99; 95% CI 1.10 to 3.58). There were no associations between smoking and atrophy in the temporal or occipital lobe, or with white matter lesions. CONCLUSION: Longstanding tobacco smoking was mainly associated with atrophy in the frontal lobe cortex. A long-term stimulation of nicotine receptors in the frontal neural pathway might be harmful for targeted brain cell.

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

BACKGROUND: 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. METHODS: 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 1 109 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. RESULTS: 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 1 000 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. CONCLUSIONS: 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.

BACKGROUND: 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. OBJECTIVE: We hypothesized that increased CSF levels of NfL and Ng are associated with subtle cognitive deficits in cognitively unimpaired (CU) older adults. METHODS: 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 ß1 - 42, total tau, and phosphorylated tau, were measured. RESULTS: 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 Aß42 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 Aß42 concentrations performed worse on the Delayed recall memory (p = 0.044). In the high Ng group, participants with pathological Aß42 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. CONCLUSION: Markers of neurodegeneration and synaptic pathology might be associated with subtle signs of cognitive decline in a population-based sample of 70-year-olds.

Screening for Mild Cognitive Impairment Using a Machine Learning Classifier and the Remote Speech Biomarker for Cognition: Evidence from Two Clinically Relevant Cohorts.

BACKGROUND: Modern prodromal Alzheimer's disease (AD) clinical trials might extend outreach to a general population, causing high screen-out rates and thereby increasing study time and costs. Thus, screening tools that cost-effectively detect mild cognitive impairment (MCI) at scale are needed. OBJECTIVE: Develop a screening algorithm that can differentiate between healthy and MCI participants in different clinically relevant populations. METHODS: Two screening algorithms based on the remote ki:e speech biomarker for cognition (ki:e SB-C) were designed on a Dutch memory clinic cohort (N = 121) and a Swedish birth cohort (N = 404). MCI classification was each evaluated on the training cohort as well as on the unrelated validation cohort. RESULTS: The algorithms achieved a performance of AUC  0.73 and AUC  0.77 in the respective training cohorts and AUC  0.81 in the unseen validation cohorts. CONCLUSION: The results indicate that a ki:e SB-C based algorithm robustly detects MCI across different cohorts and languages, which has the potential to make current trials more efficient and improve future primary health care.

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

Background: 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. Methods: 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. Results: 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. Conclusions: 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.

Representativeness in population-based studies of older adults: five waves of cross-sectional examinations in the Gothenburg H70 Birth Cohort Study.

OBJECTIVES: To describe representativeness in the Gothenburg H70 1930 Birth Cohort Study. DESIGN: Repeated cross-sectional examinations of a population-based study. SETTING: Gothenburg, Sweden. PARTICIPANTS: All residents of Gothenburg, Sweden, born on specific birth dates in 1930 were invited to a comprehensive health examination at ages 70, 75, 79, 85 and 88. The number of participants at each examination was 524 at age 70, 767 at age 75, 580 at age 79, 416 at age 85, and 258 at age 88. PRIMARY OUTCOME MEASURES: We compared register data on sociodemographic characteristics and hospital discharge diagnoses between participants and (1) refusals, (2) all same-aged individuals in Gothenburg and (3) all same-aged individuals in Sweden. We also compared mortality rates between participants and refusals. RESULTS: Refusal rate increased with age. At two or more examination waves, participants compared with refusals had higher educational level, more often had osteoarthritis, had lower mortality rates, had lower prevalence of neuropsychiatric, alcohol-related and cardiovascular disorders, and were more often married. At two examination waves, participants compared with same-aged individuals in Gothenburg had higher education and were more often born in Sweden. At two examination waves or more, participants compared with same-aged individuals in Sweden had higher education, had higher average income, less often had ischaemic heart disease, were less often born in Sweden and were more often divorced. CONCLUSIONS: Participants were more similar to the target population in Gothenburg than to refusals and same-aged individuals in Sweden. Our study shows the importance of having different comparison groups when assessing representativeness of population studies, which is important in evaluating generalisability of results. The study also contributes unique and up-to-date knowledge about participation bias in these high age groups.

Onset and rate of cognitive change before dementia diagnosis: findings from two Swedish population-based longitudinal studies.

We used data from two population-based longitudinal studies to estimate time of onset and rate of accelerated decline across cognitive domains before dementia diagnosis. The H70 includes an age-homogeneous sample (127 cases and 255 non-cases) initially assessed at age 70 with 12 follow-ups over 30 years. The Kungsholmen Project (KP) includes an age-heterogeneous sample (279 cases and 562 non-cases), with an average age of 82 years at initial assessment, and 4 follow-ups spanning 13 years. We fit mixed linear models to the data and determined placement of change points by a profile likelihood method. Results demonstrated onset of accelerated decline for fluid (speed, memory) versus crystallized (verbal, clock reading) abilities occurring approximately 10 and 5 years before diagnosis, respectively. Although decline before change points was greater for fluid abilities, acceleration was more pronounced for crystallized abilities after the change points. This suggests that onset and rate of acceleration vary systematically along the fluid-crystallized ability continuum. There is early onset in fluid abilities, but these changes are difficult to detect due to substantial age-related decline. Onset occurred later and acceleration was greater in crystallized abilities, suggesting that those markers may provide more valid identification of cases in later stages of the prodromal phase.