VasCog 2023: 20 years of research on vascular behavioural and cognitive disorders.

This Commentary describes the 20th Anniversary of VasCog 2023, held in Gothenburg, Sweden.

Estimates of Current Capacity for Diagnosing Alzheimer's Disease in Sweden and the Need to Expand Specialist Numbers.

BACKGROUND: The emergence of disease-modifying Alzheimer's (AD) treatments provides new hope to patients and families but concerns have been raised about the preparedness of healthcare systems to provide timely access to such treatments because of a combination of a complex diagnostic process and a large prevalent pool. OBJECTIVES: We assess the preparedness of Sweden, a high-income country known for its dementia-friendly policies, to diagnose AD patients eligible for treatment within a six-month window, given current capacity for specialist evaluations and biomarker testing. We calculate the investment requirements for Sweden to achieve this target over a timeframe of 20 years. DESIGN: Desk research to identify data for population, mortality, disease burden, cost of services and current capacity, expert consultation to inform assumptions about patient journey, and use of a Markov model to predict waiting times. The model simulates the patients' journey through different evaluation stages: initial evaluation by a primary care specialist, neurocognitive testing by an AD specialist, and confirmatory biomarker testing with PET scanning or cerebrospinal fluid (CSF) testing. The model assumes specialist appointments and PET scans are capacity constrained, and patients progress from cognitively normal to MCI and from MCI to dementia in the resulting waiting times. MEASUREMENTS: Projected waiting times for diagnosis of eligibility for disease-modifying Alzheimer's treatment from 2023 to 2042 assuming current capacity, assuming 20% of Swedish residents aged 60 years and above would seek an evaluation for cognitive decline. Investments required to scale capacity up to reach target of providing diagnosis within six months on average. RESULTS: Initial average waiting times for AD specialist appointments would be around 21 months in 2023 and remain around 55 months through 2042, as demand would continue to outstrip supply throughout the 20-year model horizon. Waiting times for biomarker testing would be stable at less than four weeks, as patients would be held up in the queue for their first specialist consultations, and use of CSF testing is widely accepted in Sweden. An additional 25% of AD specialists would have to be added above the current growth trend to reduce waiting times to less than 6 months at an average annual cost of approximately 805 million SEK. The increased cost of volume of biomarker testing would amount to about 106 million SEK per year. CONCLUSIONS: At current capacity, the Swedish healthcare system is unable to provide timely diagnosis of patients eligible for disease-modifying AD treatment. Although future diagnostic technologies, such as digital cognitive assessments and blood tests for the AD pathology, might decrease demand for capacity-constrained services, substantial investments will be required to meet a target of less than six months of waiting time for a diagnosis.

Plasma and cerebrospinal fluid concentrations of neurofilament light protein correlate in patients with idiopathic normal pressure hydrocephalus.

BACKGROUND: Neurofilament light chain protein (NFL), a marker of neuronal axonal degeneration, is increased in cerebrospinal fluid (CSF) of patients with idiopathic normal pressure hydrocephalus (iNPH). Assays for analysis of NFL in plasma are now widely available but plasma NFL has not been reported in iNPH patients. Our aim was to examine plasma NFL in iNPH patients and to evaluate the correlation between plasma and CSF levels, and whether NFL levels are associated with clinical symptoms and outcome after shunt surgery. METHODS: Fifty iNPH patients with median age 73 who had their symptoms assessed with the iNPH scale and plasma and CSF NFL sampled pre- and median 9 months post-operatively. CSF plasma was compared with 50 healthy controls (HC) matched for age and gender. Concentrations of NFL were determined in plasma using an in-house Simoa method and in CSF using a commercially available ELISA method. RESULTS: Plasma NFL was elevated in patients with iNPH compared to HC (iNPH: 45 (30-64) pg/mL; HC: 33 (26-50) (median; Q1-Q3), p = 0.029). Plasma and CSF NFL concentrations correlated in iNPH patients both pre- and postoperatively (r = 0.67 and 0.72, p < 0.001). We found only weak correlations between plasma or CSF NFL and clinical symptoms and no associations with outcome. A postoperative NFL increase was seen in CSF but not in plasma. CONCLUSIONS: Plasma NFL is increased in iNPH patients and concentrations correlate with CSF NFL implying that plasma NFL can be used to assess evidence of axonal degeneration in iNPH. This finding opens a window for plasma samples to be used in future studies of other biomarkers in iNPH. NFL is probably not a very useful marker of symptomatology or for prediction of outcome in iNPH.

Parity and the risk of incident dementia: a COSMIC study.

AIMS: To investigate the association between parity and the risk of incident dementia in women. METHODS: We pooled baseline and follow-up data for community-dwelling women aged 60 or older from six population-based, prospective cohort studies from four European and two Asian countries. We investigated the association between parity and incident dementia using Cox proportional hazards regression models adjusted for age, educational level, hypertension, diabetes mellitus and cohort, with additional analysis by dementia subtype (Alzheimer dementia (AD) and non-Alzheimer dementia (NAD)). RESULTS: Of 9756 women dementia-free at baseline, 7010 completed one or more follow-up assessments. The mean follow-up duration was 5.4 ± 3.1 years and dementia developed in 550 participants. The number of parities was associated with the risk of incident dementia (hazard ratio (HR) = 1.07, 95% confidence interval (CI) = 1.02-1.13). Grand multiparity (five or more parities) increased the risk of dementia by 30% compared to 1-4 parities (HR = 1.30, 95% CI = 1.02-1.67). The risk of NAD increased by 12% for every parity (HR = 1.12, 95% CI = 1.02-1.23) and by 60% for grand multiparity (HR = 1.60, 95% CI = 1.00-2.55), but the risk of AD was not significantly associated with parity. CONCLUSIONS: Grand multiparity is a significant risk factor for dementia in women. This may have particularly important implications for women in low and middle-income countries where the fertility rate and prevalence of grand multiparity are high.

Sarcopenic obesity and associations with mortality in older women and men - a prospective observational study.

BACKGROUND: The combined effect of sarcopenia and obesity, i.e., sarcopenic obesity, has been associated with disability and worse outcomes in older adults, but results are conflicting. The objectives of this study were to describe the prevalence of sarcopenic obesity (SO) in older adults, and to examine how the risk of mortality is associated with SO and its various components. METHODS: Data were obtained from two Swedish population studies, the Gothenburg H70 Birth Cohort Studies of 521 women and men at the age of 75, and the Uppsala Longitudinal Study of Adult Men (ULSAM), which included 288 men aged 87 years. Sarcopenia was defined using the recently updated EWGSOP2 definition. Obesity was defined by any of three established definitions: body mass index ≥30 kg/m2, fat mass > 30%/ > 42% or waist circumference ≥ 88 cm/≥102 cm for women and men, respectively. The Kaplan-Meier survival curve and the Cox proportional hazard model were used for 10-year and 4-year survival analyses in the H70 and ULSAM cohorts, respectively. RESULTS: SO was observed in 4% of the women and 11% of the men in the H70 cohort, and in 10% of the ULSAM male cohort. The 75-year-old women with SO had a higher risk (HR 3.25, 95% confidence interval (1.2-8.9)) of dying within 10 years compared to those with a "normal" phenotype. A potential similar association with mortality among the 75-year-old men was not statistically significant. In the older men aged 87 years, obesity was associated with increased survival. CONCLUSIONS: SO was observed in 4-11% of community-dwelling older adults. In 75-year-old women SO appeared to associate with an increased risk of dying within 10 years. In 87-year-old men, the results indicated that obesity without sarcopenia was related to a survival benefit over a four-year period.

Epidemiology of suicidal feelings in an ageing Swedish population: from old to very old age in the Gothenburg H70 Birth Cohort Studies.

AIMS: The first aim of this study was to provide prevalence suicidal feelings over time (past week, past month, past year and lifetime) in a population-based sample of old to very old adults without dementia. Does prevalence change with rising age? The second aim was to examine the fluctuation of suicidal feelings over time. How does this coincide with depression status? METHODS: Data were derived from the Gothenburg H70 Birth Cohort Studies (the H70 studies) which are multidisciplinary longitudinal studies on ageing. A representative sample of adults in Gothenburg, Sweden with birth years 1901-1944 were invited to take part in a longitudinal health study on ageing and participated at one or more occasions during 1986-2014. The sample consisted of 6668 observations originating from 3972 participants without dementia between the ages of 70 and 108, including 1604 participants with multiple examination times. Suicidal feelings were examined during a psychiatric interview using the Paykel questions (life not worth living, death wishes, thoughts of taking own life, seriously considered taking life, attempted suicide). RESULTS: Prevalence figures for suicidal feelings of any severity were as follows: past week 4.8%, past month 6.7%, past year 11.2% and lifetime 25.2%. Prevalence rates increased with age in the total group and in women but not in men. Suicidal feelings were common in participants with concurrent major or minor depression, but over a third of the participants who reported suicidal feelings did not fulfil criteria for these diagnoses nor did they present elevated mean depressive symptom scores. The majority of participants consistently reported no experience of suicidal feelings over multiple examination times, but fluctuation was more common in women compared with men. CONCLUSION: Suicidal feelings in late-life are uncommon in individuals without depression indicating that such behaviour is not a widespread, normative phenomenon. However, such feelings may occur outside the context of depression.

Atrial fibrillation increases the risk of dementia amongst older adults even in the absence of stroke.

BACKGROUND: Atrial fibrillation increases risk of stroke, and thus risk of cognitive impairment and dementia. Emerging evidence suggests an association also in the absence of stroke. We aimed to examine the association between atrial fibrillation and incident dementia, with and without exclusion of individuals with stroke, and if sex and genetic factors modify the possible association. METHODS: In 2000-2001, a population-based sample of 70-year-olds (N = 561) underwent comprehensive somatic and neuropsychiatric examinations, as part of the Gothenburg H70 Birth Cohort Studies. Participants were followed up at age 75 and 79. Atrial fibrillation at baseline was identified through ECG, proxy-reports and the National Patient Register (NPR). Stroke at baseline and follow-up was identified through self-reports, proxy-reports and the NPR. Dementia at baseline and follow-up was diagnosed according to the DSM-III-R criteria based on neuropsychiatric examinations, proxy-reports and the NPR. RESULTS: Individuals with atrial fibrillation had an almost threefold increased risk of dementia during 12-year follow-up (HR 2.8; 95% CI 1.3-5.7; P = 0.004), and this risk remained after excluding individuals with stroke at baseline and follow-up. After stratification for sex, the association was only found amongst men (HR 4.6; 95% CI 1.9-11.2; P < 0.001, interaction sex*atrial fibrillation; P = 0.047) and noncarriers of the APOE ε4 allele (HR 4.2; 95% CI 1.8-9.7; P < 0.001, interaction APOE*atrial fibrillation; P = 0.128). Population attributable risk for dementia resulting from atrial fibrillation was 13%. CONCLUSION: The relevance for atrial fibrillation as an indicator of subclinical brain vascular risk needs to be further explored. In addition, patients with atrial fibrillation should be screened for cognitive symptoms.

Depression and neuroticism decrease among women but not among men between 1976 and 2016 in Swedish septuagenarians.

OBJECTIVES: We evaluated birth-cohort differences in depressive symptom burden, prevalence of depression diagnoses, and neuroticism, among Swedish 70-year-olds examined between 1976 and 2016. METHODS: We used a repeated cross-sectional design examining four representative population samples of Swedish 70-year-olds (total n = 2279) with identical methods in 1976-77 (n = 392), 1992-93 (n = 226), 2000-02 (n = 487), and 2014-16 (n = 1166). Depressive symptom burden was rated with the Montgomery Åsberg Depression Rating Scale. Major depression was diagnosed according to DSM-5, and minor depression according to DSM-IV-TR research criteria. Neuroticism was rated with the Eysenck Personality Inventory. RESULTS: For women in 2014-16, MADRS score (4.4 vs. 6.1 vs. 5.8; P < 0.05) and neuroticism (6.6 vs. 7.7 vs. 9.2; P < 0.05) were lower compared with 1992-93 and 1976-77, and the prevalence of any depression was lower compared with 2000-02 and 1992-93 (10.9% vs. 16.9% vs. 18.1%; P < 0.05). For men, we observed no birth-cohort differences in depression, while neuroticism was found to be lower in 2014-16 compared with 1976-77 among men without depression (5.1 vs. 5.9; P < 0.01). The sex difference for MADRS and neuroticism declined between 1976-77 and 2014-16 (cohort*sex P < 0.05). CONCLUSIONS: Depressive burden and neuroticism decreased in 70-year-old women between 1976 and 2016.

Publisher Correction: Preclinical amyloid pathology biomarker positivity: effects on tau pathology and neurodegeneration.

The Article was originally published under a CC BY-NC-ND 4.0 license, but has now been made available under a CC BY 4.0 license. The PDF and HTML versions of the Article have been modified accordingly.

CSF YKL-40 and GAP-43 are related to suicidal ideation in older women.

OBJECTIVE: To investigate possible relationships between suicidal ideation and cerebrospinal fluid (CSF) levels of glial markers YKL-40 (also known as chitinase-3-like protein 1), growth-associated protein-43 (GAP-43) and myelin basic protein (MBP). METHOD: The sample was obtained from the Prospective Population Study of Women and included 86 women without dementia who underwent both psychiatric examinations and lumbar puncture (LP). Eight of these women reported past-month suicidal ideation. RESULTS: Significantly, higher CSF levels of both YKL-40 and GAP-43 were detected in women with past-month suicidal ideation. Associations with suicidal ideation remained for both YKL-40 and GAP-43 in regression models adjusted for smoking status, BMI and age. CSF levels of YKL-40, GAP-43 and MBP did not differ by depression status. Higher levels of CSF GAP-43 were associated with feelings of worthlessness; a strong relationship was demonstrated in the fully adjusted model (OR 5.95 CI [1.52-23.20], P = 0.01). CONCLUSION: Our findings of elevated CSF concentrations of both YKL-40 and GAP-43 in women with suicidal ideation, compared to those without, suggest that a disrupted synaptic glial functioning and inflammation may be related to the aetiology of suicidal ideation in older adults.

Estimated ventricle size using Evans index: reference values from a population-based sample.

BACKGROUND AND PURPOSE: Evans index is an estimate of ventricular size used in the diagnosis of idiopathic normal-pressure hydrocephalus (iNPH). Values >0.3 are considered pathological and are required by guidelines for the diagnosis of iNPH. However, there are no previous epidemiological studies on Evans index, and normal values in adults are thus not precisely known. We examined a representative sample to obtain reference values and descriptive data on Evans index. METHODS: A population-based sample (n = 1235) of men and women aged ≥70 years was examined. The sample comprised people living in private households and residential care, systematically selected from the Swedish population register. Neuropsychiatric examinations, including head computed tomography, were performed between 1986 and 2000. RESULTS: Evans index ranged from 0.11 to 0.46. The mean value in the total sample was 0.28 (SD, 0.04) and 20.6% (n = 255) had values >0.3. Among men aged ≥80 years, the mean value of Evans index was 0.3 (SD, 0.03). Individuals with dementia had a mean value of Evans index of 0.31 (SD, 0.05) and those with radiological signs of iNPH had a mean value of 0.36 (SD, 0.04). CONCLUSIONS: A substantial number of subjects had ventricular enlargement according to current criteria. Clinicians and researchers need to be aware of the range of values among older individuals.

Preclinical amyloid pathology biomarker positivity: effects on tau pathology and neurodegeneration.

Brain autopsy and biomarker studies indicate that the pathology of Alzheimer's disease (AD) is initiated at least 10-20 years before clinical symptoms. This provides a window of opportunity to initiate preventive treatment. However, this emphasizes the necessity for biomarkers that identify individuals at risk for developing AD later in life. In this cross-sectional study, originating from three epidemiologic studies in Sweden (n=1428), the objective was to examine whether amyloid pathology, as determined by low cerebrospinal fluid (CSF) concentration of the 42 amino acid form of ß-amyloid (Aß42), is associated with biomarker evidence of other pathological changes in cognitively healthy elderly. A total of 129 patients were included and CSF levels of Aß42, total tau, tau phosphorylated at threonine 181 (p-tau), neurogranin, VILIP-1, VEGF, FABP3, Aß40, neurofilament light, MBP, orexin A, BDNF and YKL-40 were measured. Among these healthy elderly, 35.6% (N=46) had CSF Aß42 levels below 530 pg ml-1. These individuals displayed significantly higher CSF concentrations of t-tau (P<0.001), p-tau (181) (P<0.001), neurogranin (P=0.009) and FABP3 (P=0.044) compared with amyloid-negative individuals. Our study indicates that there is a subpopulation among healthy older individuals who have amyloid pathology along with signs of ongoing neuronal and synaptic degeneration, as well as tangle pathology. Previous studies have demonstrated that increase in CSF tau and p-tau is a specific sign of AD progression that occurs downstream of the deposition of Aß. On the basis of this, our data suggest that these subjects are at risk for developing AD. We also confirm the association between APOE ɛ4 and amyloid pathology in healthy older individuals.

Longitudinal associations between physical activity and depression scores in Swedish women followed 32 years.

OBJECTIVE: Physical activity is negatively associated with depressive symptoms. However, few studies consider dynamic associations of changes in physical activity and reciprocal relationships. This study aimed to perform comprehensive evaluations of relationships between physical activity and depression scores in women followed from mid- to late life. METHOD: The Prospective Population Study of Women in Gothenburg, Sweden, provided repeated measures of self-reported physical activity and depressive symptoms between 1974 and 2005 (baseline N = 676, 84.5% response rate). Depressive symptoms were assessed using the Montgomery-Åsberg Depression Rating Scale, and physical activity was evaluated by the Saltin-Grimby Physical Activity Level Scale. Latent growth curve analyses were used to evaluate associations of change, and cross-lagged models were used to study the reciprocal relationship between physical activity and depression scores. RESULTS: At baseline, lower levels of physical activity were related to higher depression scores. Individuals with decreasing physical activity over time evidenced higher depression scores at 32-year follow-up. Higher average baseline depression score was related to declining levels of physical activity at subsequent examinations. CONCLUSION: Reduced physical activity may be a long-term consequence of depression. It is important to address individual changes in physical activity and not merely absolute levels of physical activity in relationship to depression.

White matter lesions and temporal lobe atrophy related to incidence of both dementia and major depression in 70-year-olds followed over 10 years.

BACKGROUND AND PURPOSE: A number of studies have suggested associations between dementia and depression in older adults. One reason could be that these disorders share structural correlates, such as white matter lesions (WMLs) and cortical atrophy. No study has examined whether these lesions precede both dementia and depression independently of each other in the general population. METHODS: Whether WMLs and cortical atrophy on computed tomography predict dementia and depression was investigated in a population-based sample of 70-year-olds (n = 380) followed over 10 years. Exclusion criteria were dementia, major depression, history of stroke and a Mini-Mental State Examination score below 26 at baseline in 2000-2001. Dementia was diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, third edition, revised, and depression according to the Diagnostic and Statistical Manual of Mental Disorders, fifth edition. Primary outcomes included dementia and major depression at 10-year follow-up. RESULTS: Adjusted logistic regression models, including both WMLs and temporal lobe atrophy, showed that moderate to severe WMLs [odds ratio (OR) 3.96, 95% confidence interval (CI) 1.23-12.76] and temporal lobe atrophy (OR 2.93, 95% CI 1.13-7.60) predicted dementia during a 10-year follow-up independently of major depression. Similarly, both moderate to severe WMLs (OR 3.84, 95% CI 1.25-11.76) and temporal lobe atrophy (OR 2.52, 95% CI 1.06-5.96) predicted depression even after controlling for incident dementia. CONCLUSION: White matter lesions and temporal lobe atrophy preceded 10-year incidence of both dementia and depression in 70-year-olds. Shared structural correlates could explain the reported associations between dementia and depression. These brain changes may represent independent and complementary pathways to dementia and depression. Strategies to slow progression of vascular pathology and neurodegeneration could indirectly prevent both dementia and depression in older adults.

Advances in the prevention of Alzheimer's disease and dementia.

BACKGROUND: Definitions and diagnostic criteria for all medical conditions are regularly subjected to reviews and revisions as knowledge advances. In the field of Alzheimer's disease (AD) research, it has taken almost three decades for diagnostic nomenclature to undergo major re-examination. The shift towards presymptomatic and pre-dementia stages of AD has brought prevention and treatment trials much closer to each other than before. METHODS: Here we discuss: (i) the impact of diagnostic reliability on the possibilities for developing preventive strategies for AD; (ii) the scientific evidence to support moving from observation to action; (iii) ongoing intervention studies; and (iv) the methodological issues and prospects for balancing strategies for high-risk individuals with those for broad population-based prevention. RESULTS: The associations between neuropathology and cognition are still not entirely clear. In addition, the risk factors for AD dementia and the neuropathological hallmarks of AD may not necessarily be the same. Cognitive impairment has a clearer clinical significance and should therefore remain the main focus of prevention. Risk/protective factors for dementia/AD need to be studied from a life-course perspective. New approaches in prevention trials include enrichment strategies based on genetic risk factors or beta-amyloid biomarkers (at least four ongoing pharmacological trials), and multidomain interventions simultaneously targeting various vascular and lifestyle-related risk factors (at least three ongoing trials). Experience from prevention programmes in other chronic diseases can provide additional methodological improvements. CONCLUSIONS: Building infrastructures for international collaborations is necessary for managing the worldwide public health problem of AD and dementia. The International Database on Aging and Dementia (IDAD) and the European Dementia Prevention Initiative (EDPI) are examples of ongoing international efforts aiming to improve the methodology of preventive studies and provide the basis for larger intervention trials.

A 37-year prospective study of neuroticism and extraversion in women followed from mid-life to late life.

OBJECTIVE: Personality traits are presumed to endure over time, but the literature regarding older age is sparse. Furthermore, interpretation may be hampered by the presence of dementia-related personality changes. The aim was to study stability in neuroticism and extraversion in a population sample of women who were followed from mid-life to late life. METHOD: A population-based sample of women born in 1918, 1922 or 1930 was examined with the Eysenck Personality Inventory (EPI) in 1968-1969. EPI was assessed after 37 years in 2005-2006 (n = 153). Data from an interim examination after 24 years were analysed for the subsample born in 1918 and 1922 (n = 75). Women who developed dementia at follow-up examinations were excluded from the analyses. RESULTS: Mean levels of neuroticism and extraversion were stable at both follow-ups. Rank-order and linear correlations between baseline and 37-year follow-up were moderate ranging between 0.49 and 0.69. Individual changes were observed, and only 25% of the variance in personality traits in 2005-2006 could be explained by traits in 1968-1969. CONCLUSION: Personality is stable at the population level, but there is significant individual variability. These changes could not be attributed to dementia. Research is needed to examine determinants of these changes, as well as their clinical implications.

Secular trends in the prevalence of dementia and depression in Swedish septuagenarians 1976-2006.

BACKGROUND: It is not clear whether the prevalence of dementia and depression among the elderly has changed during the past 30 years. METHOD: Population-based samples from Gothenburg, Sweden were examined with identical psychiatric and neuropsychiatric examinations at age 70 years in 1976-1977 (n = 404, response rate 78.8%) and 2000-2001 (n = 579, response rate 66.4%), and at age 75 in 1976-1977 (n = 303, response rate 78%) and 2005-2006 (n = 753, response rate 63.4%). Depression was diagnosed according to DSM-IV and dementia according to Kay's criteria. General linear models (GLMs) were used to test for differences between groups. RESULTS: Dementia was related to age but not to birth cohort or sex. Major depression was related to sex (higher in women) but not to birth cohort or age. Minor depression was related to birth cohort, sex (higher in women), age (higher at age 75) and the interaction effect of birth cohort × age; that is, the prevalence of minor depression increased with age in the 2000s but not in the 1970s. Thus, the prevalence of minor depression was higher in 2005-2006 than in 1976-1977 among 75-year-olds for both men (12.4% v. 3.7%) and women (19.1% v. 5.6%) whereas there were no birth cohort differences at age 70. CONCLUSIONS: Secular changes were observed only for minor depression, which is considered to be related more to psychosocial factors than major depression. The high prevalence of minor depression in later-born birth cohorts emphasizes the importance of detecting minor depression in the elderly.

Secular changes in personality: study on 75-year-olds examined in 1976-1977 and 2005-2006.

OBJECTIVE: In order to study secular changes in personality factors neuroticism and extroversion, representative population samples of non-demented 75-year-olds underwent psychiatric examinations in 1976-1977 (total n = 223, 138 women, 85 men) and 2005-2006 (total n = 556, 322 women and 234 men). METHODS: Eysenck Personality Inventory was used at both occasions. Demographic factors (educational level, marital status, having children) were registered. RESULTS: Seventy-five-year-olds examined in 2005-2006 had higher values on extroversion and lower values on the Lie scale compared with those examined in 1976-1977. Neuroticism did not differ between the two birth cohorts. Neuroticism scores were higher in women than in men both in 1976-1977 and 2005-2006, and Lie score was higher in women than in men in 2005-2006. CONCLUSIONS: Our findings suggest that present cohorts of 75-year-olds are more extroverted and less prone to respond in a socially desirable manner than those born three decades earlier. Neuroticism levels remained unchanged, suggesting this trait may be less influenced by environmental factors than the other traits studied.

A population-based study on the influence of brain atrophy on 20-year survival after age 85.

BACKGROUND: Individuals aged 80 years and older is the fastest growing segment of the population worldwide. To understand the biology behind increasing longevity, it is important to examine factors related to survival in this age group. The relationship between brain atrophy and survival after age 85 remains unclear. METHODS: A population-based sample (n = 239) had head CT scans at age 85 and was then followed until death. Cortical atrophy and ventricular size were assessed. Statistical analyses included Cox proportional hazards models with time to death as the outcome and considering a large number of possible confounders, including baseline cognitive function, incident dementia, and somatic disorders. RESULTS: Mean survival time (±SD) was 5.0 ± 3.6 years (range 0.10-19.8 years). Decreased survival was associated with temporal, and frontal atrophy, sylvian fissure width and a number of ventricular measures after adjustment for potential confounders. In participants without dementia at baseline (n = 135), decreased survival was associated with temporal lobe atrophy and bifrontal ratio. In those with dementia (n = 104), decreased survival was associated with third ventricle width, cella media ratio, and ventricle-to-brain and ventricle-to-cranial ratio. CONCLUSIONS: Several indices of brain atrophy were related to decreased survival after age 85, regardless of dementia status. Brain atrophy is rarely mentioned as a significant indicator of survival in the elderly, independent of traditional predictors such as cardiovascular disease or cancer. The biology behind the influence of brain atrophy on survival needs to be further scrutinized.

The 32-year relationship between cholesterol and dementia from midlife to late life.

BACKGROUND: Cellular and animal studies suggest that hypercholesterolemia contributes to Alzheimer disease (AD). However, the relationship between cholesterol and dementia at the population level is less clear and may vary over the lifespan. METHODS: The Prospective Population Study of Women, consisting of 1,462 women without dementia aged 38-60 years, was initiated in 1968-1969 in Gothenburg, Sweden. Follow-ups were conducted in 1974-1975, 1980-1981, 1992-1993, and 2000-2001. All-cause dementia was diagnosed according to DSM-III-R criteria and AD according to National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria. Cox proportional hazards regression examined baseline, time-dependent, and change in cholesterol levels in relation to incident dementia and AD among all participants. Analyses were repeated among participants who survived to the age of 70 years or older and participated in the 2000-2001 examination. RESULTS: Higher cholesterol level in 1968 was not associated with an increased risk of AD (highest vs lowest quartile: hazard ratio [HR] 2.82, 95% confidence interval [CI] 0.94-8.43) among those who survived to and participated in the 2000-2001 examination. While there was no association between cholesterol level and dementia when considering all participants over 32 years, a time-dependent decrease in cholesterol over the follow-up was associated with an increased risk of dementia (HR 2.35, 95% CI 1.22-4.58). CONCLUSION: These data suggest that midlife cholesterol level is not associated with an increased risk of AD. However, there may be a slight risk among those surviving to an age at risk for dementia. Declining cholesterol levels from midlife to late life may better predict AD risk than levels obtained at one timepoint prior to dementia onset. Analytic strategies examining this and other risk factors across the lifespan may affect interpretation of results.