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.

Frailty-Related Factors among Women Living with and without HIV Aged 40 Years and Older. The Women's Interagency HIV Study.

BACKGROUND: Frailty is a clinical, geriatric syndrome linked to disability and mortality; and may be associated with a variety of factors among underrepresented and underserved women living with HIV (WLWH) and without HIV (WLWOH) transitioning through the adult life course. OBJECTIVES: Determine whether a published set of factors associated cross-sectionally with frailty in WLWH and similar WLWOH at average age 39 years in 2005/2006 were associated with frailty in 2018/2019 among women who initiated frailty assessments at age ≥40 years, or whether a new set of factors were associated with frailty. DESIGN: Cross-sectional analyses within a longitudinal cohort study. SETTING: The multi-center Women's Interagency HIV Study (WIHS). PARTICIPANTS: 1285 participants (951 WLWH, 334 WLWOH), median age 53 years (interquartile range 47-58 years). MEASUREMENTS: The Fried Frailty Phenotype (FFP) in association with 23 factors representing HIV serostatus, other infections, sociodemographic factors, health behaviors, and chronic diseases. RESULTS: Frailty prevalence was 11.1% in 2018/2019 (12.6% among WLWOH, 9.6% among WLWH, p=0.121). The published 2005/2006 final multivariable stepwise regression model contained 9 predictors of frailty. When refit to women in 2018/2019, only age ≥50 years and annual income ≤$12,000 were independently positively associated with frailty; other significant 2005/2006 factors, HIV serostatus, CD4+ count <500 cells/mL among WLWH, smoking, drinking, FIB-4 and eGFR, were not. A newly-derived stepwise model considering all 23 predictors measured in 2018/2019, showed independent positive associations between frailty and age ≥50 years, annual income ≤$12,000, obesity (body mass index (BMI) ≥30kg/m2), and history of tuberculosis and cancer. CONCLUSION: Different chronic and infectious disease factors were associated with frailty among WLWH and WLWOH over the adult life course. Understanding factors associated with frailty by adult life stage, allows identification and implementation of novel, temporal interventions to alleviate frailty-associated outcomes and enhance quality of life among WLWH and WLWOH.

Frailty and Constellations of Factors in Aging HIV-infected and Uninfected Women--The Women's Interagency HIV Study.

BACKGROUND: Biological similarities are noted between aging and HIV infection. Middle-aged adults with HIV infection may present as elderly due to accelerated aging or having more severe aging phenotypes occurring at younger ages. OBJECTIVES: We explored age-adjusted prevalence of frailty, a geriatric condition, among HIV+ and at risk HIV- women. DESIGN: Cross-sectional. SETTING: The Women's Interagency HIV Study (WIHS). PARTICIPANTS: 2028 middle-aged (average age 39 years) female participants (1449 HIV+; 579 HIV-). MEASUREMENTS: The Fried Frailty Index (FFI), HIV status variables, and constellations of variables representing Demographic/health behaviors and Aging-related chronic diseases. Associations between the FFI and other variables were estimated, followed by stepwise regression models. RESULTS: Overall frailty prevalence was 15.2% (HIV+, 17%; HIV-, 10%). A multivariable model suggested that HIV infection with CD4 count<200; age>40 years; current or former smoking; income ≤$12,000; moderate vs low fibrinogen-4 (FIB-4) levels; and moderate vs high estimated glomerular filtration rate (eGFR) were positively associated with frailty. Low or moderate drinking was protective. CONCLUSIONS: Frailty is a multidimensional aging phenotype observed in mid-life among women with HIV infection. Prevalence of frailty in this sample of HIV-infected women exceeds that for usual elderly populations. This highlights the need for geriatricians and gerontologists to interact with younger 'at risk' populations, and assists in the formulation of best recommendations for frailty interventions to prevent early aging, excess morbidities and early death.

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.

Factors related to disability: evidence from the "Treviso Longeva (TRELONG) study".

Prolongation of life is an important public health goal as long as there is an emphasis on the quality of life (QoL) and independent living. Diminishing abilities to ambulate and participate in activities of daily living point to a serious decline in functional health, increasing the risk of institutionalization and death. In our work we found a pattern of factors associated with disability, especially cognitive impairment, as well as stroke, physical activity and performance, reading, and the nutritional biomarkers, blood albumin and high-density lipoprotein cholesterol (HDL-C). The attention to this cluster of markers, suggesting multidimensional prevention, may have unexpected good effects against disability.

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.

The ACE Insertion Deletion polymorphism relates to dementia by metabolic phenotype, APOEepsilon4, and age of dementia onset.

The renin-angiotensin system (RAS) may play a role in dementia pathogenesis because of its effects on vascular and metabolic homeostasis, amyloid metabolism, and learning and memory. The angiotensin-converting enzyme (ACE), a pivotal RAS protein, is encoded for by a gene containing a functional ID variant, which has been related to dementia risk. We examined the relationship between the ACE Insertion Deletion (ACE ID) variant and dementia with consideration for metabolic phenotypes, age and APOEepsilon4 using a population-based, cross-sectional sample of 891 Swedish women and men aged 70-92 years, of whom 61 people were demented. The odds of dementia was two-fold higher among those with ACE II genotype, and ranged from 2.18 to 4.35 among those with dementia onset

Adiposity indicators and dementia over 32 years in Sweden.

BACKGROUND: High midlife and late-life adiposity may increase risk for dementia. Late-life decrease in body mass index (BMI) or body weight within several years of a dementia diagnosis has also been reported. Differences in study designs and analyses may provide different pictures of this relationship. METHODS: Thirty-two years of longitudinal body weight, BMI, waist circumference, and waist-to-hip ratio (WHR) data, from the Prospective Population Study of Women in Sweden, were related to dementia. A representative sample of 1,462 nondemented women was followed from 1968 at ages 38-60 years, and subsequently in 1974, 1980, 1992, and 2000, using neuropsychiatric, anthropometric, clinical, and other measurements. Cox proportional hazards regression models estimated incident dementia risk by baseline factors. Logistic regression models including measures at each examination were related to dementia among surviving participants 32 years later. RESULTS: While Cox models showed no association between baseline anthropometric factors and dementia risk, logistic models showed that a midlife WHR greater than 0.80 increased risk for dementia approximately twofold (odds ratio 2.22, 95% confidence interval 1.00-4.94, p = 0.049) among surviving participants. Evidence for reverse causality was observed for body weight, BMI, and waist circumference in years preceding dementia diagnosis. CONCLUSIONS: Among survivors to age 70, high midlife waist-to-hip ratio may increase odds of dementia. Traditional Cox models do not evidence this relationship. Changing anthropometric parameters in years preceding dementia onset indicate the dynamic nature of this seemingly simple relationship. There are midlife and late-life implications for dementia prevention, and analytical considerations related to identifying risk factors for dementia.

Central obesity and increased risk of dementia more than three decades later.

BACKGROUND: Numerous reports show that a centralized distribution of adiposity is a more dangerous risk factor for cardiovascular disease and diabetes than total body obesity. No studies have evaluated whether the same pattern exists with dementia. The objective was to evaluate the association between midlife central obesity and risk of dementia three decades later. METHODS: A longitudinal analysis was conducted of 6,583 members of Kaiser Permanente of Northern California who had their sagittal abdominal diameter (SAD) measured in 1964 to 1973. Diagnoses of dementia were from medical records an average of 36 years later, January 1, 1994, to June 16, 2006. Cox proportional hazard models adjusted for age, sex, race, education, marital status, diabetes, hypertension, hyperlipidemia, stroke, heart disease, and medical utilization were conducted. RESULTS: A total of 1,049 participants (15.9%) were diagnosed with dementia. Compared with those in the lowest quintile of SAD, those in the highest had nearly a threefold increased risk of dementia (hazard ratio, 2.72; 95% CI, 2.33-3.33), and this was only mildly attenuated after adding body mass index (BMI) to the model (hazard ratio, 1.92; 95% CI, 1.58-2.35). Those with high SAD (>25 cm) and normal BMI had an increased risk (hazard ratio, 1.89; 95% CI, 0.98-3.81) vs those with low SAD (<25 cm) and normal BMI (18.5-24.9 kg/m(2)), whereas those both obese (BMI >30 kg/m(2)) and with high SAD had the highest risk of dementia (HR, 3.60; 95% CI, 2.85-4.55). CONCLUSIONS: Central obesity in midlife increases risk of dementia independent of diabetes and cardiovascular comorbidities. Fifty percent of adults have central obesity; therefore, mechanisms linking central obesity to dementia need to be unveiled.

Mid-life adiposity factors relate to blood-brain barrier integrity in late life.

OBJECTIVE: We explored the relationship between adiposity factors measured during mid-life and blood-brain barrier (BBB) integrity measured via the cerebrospinal fluid/serum (CSF/S) albumin ratio in late life. Adiposity factors included body mass index and blood levels of sex hormone binding globulin (SHBG) and leptin. Design. Retrospective analyses over 24 years within a longitudinal study. SETTING: Population-based sample. Subjects. Eighty-one women. MAIN OUTCOME MEASURES: CSF/S albumin ratio. RESULTS: The CSF/S albumin ratio measured at age 70-84 years was higher amongst women who were overweight or obese (6.50 +/- 2.79 vs. 5.23 +/- 1.61, age-adjusted P = 0.012), and was inversely correlated with SHBG (age-adjusted r = -0.321, P < 0.005) at age 46-60 years. In stepwise regression models, SHBG predicted the CSF/S albumin ratio (beta = -0.017, R2 = 0.107, P = 0.007). The best model (R2 = 0.187) predicting CSF/S albumin ratio included SHBG, age group (age 46 years versus >46), overweight or obesity, and an age group by SHBG interaction. CONCLUSIONS: Lower levels of SHBG in mid-life were related to worse BBB integrity in women after 24 years in late life, even considering other adiposity factors. SHBG may be important for understanding sex hormone-mediated mechanisms in brain health or as an independent marker of adipose tissue, the largest endocrine organ.

Body mass index and white matter lesions in elderly women. An 18-year longitudinal study.

BACKGROUND: We investigated the longitudinal relationship between body mass index (BMI), a major vascular risk factor, and white matter lesions (WMLs) in older women. METHODS: Twenty-seven Swedish women were followed from age 70 to 88. Measurements of BMI, and systolic and diastolic blood pressures were conducted at 70, 75, 79, 85, and 88 years. WMLs were measured using computerized tomography at age 85 and 88 (85/88). RESULTS: Women with any WMLs at age 85/88 had higher BMI at age 70 (p = 0.003) and 75 (p = 0.006), compared to women without WMLs. Increasing severity of WMLs was related to BMI at age 70 (p < 0.001), 75 (p < 0.001), 79 (p = 0.017), and 85 (p = 0.025). After consideration of other vascular factors, BMI at age 70, 75, and 79 was most significantly related to WML at 85/88. Every 1.0 kg/m2 increase in BMI at age 70 increased risk of WMLs twofold. CONCLUSIONS: Overweight and obesity may be important contributors to the presence of WMLs in the elderly.

Androgen receptor gene repeats and indices of obesity in older adults.

OBJECTIVE: To examine the relationship between GGN and CAG trinucleotide repeat polymorphisms in the androgen receptor (AR) gene and indices of obesity in older Caucasian adults. DESIGN: A cross-sectional study. SUBJECTS: Ninety-nine healthy men (age 51-93 y) and 113 healthy postmenopausal women (age 51-92 y). MEASUREMENTS: Genotyping the GGN and CAG repeats of the AR gene, and measuring body weight, height and waist and hip circumferences. Waist was measured at the umbilicus (wstumb), iliac crest (wstili), and mid-way between the iliac crest and lowest rib (wstwst). Waist-to-hip ratios (WHRUMB, WHRILI and WHRWST) and body mass index (BMI) were calculated. RESULTS: Women who were homozygous for a common GGN (17 or 18) and short CAG (

Appetite is not influenced by a unique milk peptide: caseinomacropeptide (CMP).

The milk protein, caseinomacropeptide (CMP), is a predominant breakdown product of casein in the human stomach, and may aid in the regulation of food intake. Using a human feeding study design, this project assessed the effects of CMP on satiety and satiation by measuring the amount of food consumed at meal times and through subjective motivation to eat questionnaires. The following beverage treatments were prepared: 0.4% CMP solution, 2.0% CMP solution, vehicle alone, and water containing colorant and clouding agent. Twenty male and 32 female adults were enrolled into the study using a Latin Square randomization. Treatment beverages and ad libitum lunches were consumed on four separate occasions at the Study Center. After lunch, subjects left the Study Center, and completed a standardized questionnaire every hour throughout the afternoon and evening to assess hunger and stomach fullness, and kept track of all food and beverages consumed. Under these experimental conditions, CMP had no effect on energy intake or weight of food consumed at lunch or for the remainder of the day. CMP also had no effect on subjective indicators of satiety. Intake of CMP before a midday meal has no effect on regulation of food intake over a short-term period.

Effects of 4 hand-drying methods for removing bacteria from washed hands: a randomized trial.

OBJECTIVE: To evaluate the effects of 4 different drying methods to remove bacteria from washed hands. SUBJECTS AND METHODS: One hundred adult volunteers participated in this randomized prospective study. All bacterial counts were determined using a modified glove-juice sampling procedure. The difference was determined between the amounts of bacteria on hands artificially contaminated with the bacterium Micrococcus luteus before washing with a nonantibacterial soap and after drying by 4 different methods (cloth towels accessed by a rotary dispenser, paper towels from a stack on the hand-washing sink, warm forced air from a mechanical hand-activated dryer, and spontaneous room air evaporation). The results were analyzed using a nonparametric analysis (the Friedman test). By this method, changes in bacterial colony-forming unit values for each drying method were ranked for each subject. RESULTS: The results for 99 subjects were evaluable. No statistically significant differences were noted in the numbers of colony-forming units for each drying method (P = .72). CONCLUSION: These data demonstrate no statistically significant differences in the efficiency of 4 different hand-drying methods for removing bacteria from washed hands.

Urinary isoflavonoid and lignan excretion on a Western diet: relation to soy, vegetable, and fruit intake.

Dietary isoflavone and lignan phytoestrogens are potential chemopreventive agents. This has led to a need to monitor exposure to these compounds in human populations and to determine which components of a mixed diet contribute to the exposure. Typically, urinary isoflavonoid excretion is associated with soy consumption and that of lignans is associated with whole grains. However, other plant foods are known to contain phytoestrogen precursors. The purpose of this study was to examine the association between urinary isoflavonoid and lignan excretion and intakes of vegetables and fruits (V&F). Isoflavonoids (genistein, daidzein, O-desmethylangolensin, and equol) and lignans (enterolactone, enterodiol, and matairesinol) were measured in urine collected for 3 days from 49 male and 49 female volunteers (age, 18-37 years) reporting a wide range of habitual V&F intakes. Dietary intakes were assessed using 5-day diet records and a food frequency questionnaire. V&F groupings (total V&F, total V, total F, soyfoods, and V&F grouped by botanical families) were used to assess the relationship between V&F intake and urinary isoflavonoid and lignan excretion. Pearson correlations were performed. Intake of soyfoods was correlated significantly with urinary genistein (r = 0.40; P = 0.0001), O-desmethylangolensin (r = 0.37; P = 0.0002), daidzein (r = 034; P = 0.0007), and the sum of isoflavonoids (r = 0.39; P = 0.0001). There was no association between equol excretion and soy intake or between the isoflavonoids and any other V&F groupings. In addition, isoflavonoid excretion was correlated positively with intake of high-fat and processed meats, particularly among men who did not consume soy. This suggests that, even in the United States, on a Western diet, soyfoods are the primary contributors to isoflavone intake; however, additional "hidden sources" of soy may also contribute to exposure. In contrast, a variety of fiber-containing foods contributed to lignan excretion; the sum of the urinary lignans, enterodiol, enterolactone, and matairesinol, was associated with intake of total F (r = 0.27; P = 0.008), total V&F (r = 0.25; P = 0.01), soyfoods (r = 0.28; P = 0.006), and dietary fiber (r = 0.36; P = 0.0003). Overall, urinary phytoestrogens (isoflavonoids + lignans) were significantly higher in "high" compared with "low" V&F consumers. Compared with the "low" V&F group, the "high" group consumed diets that were, on average, higher in fiber and carbohydrate and soyfoods and lower in fat; thus, the urinary phytoestrogens may also be a useful marker of healthier dietary patterns.

Well-done meat intake and the risk of breast cancer.

BACKGROUND: Heterocyclic amines, mutagens formed in meats cooked at high temperatures, have been demonstrated as mammary carcinogens in animals. We conducted a nested, case-control study among 41836 cohort members of the Iowa Women's Health Study to evaluate the potential role of heterocyclic amines and intake of well-done meat in the risk for human breast cancer. METHODS: A questionnaire was mailed to individuals in the cohort who had breast cancer diagnosed during the period from 1992 through 1994 and a random sample of cancer-free cohort members to obtain information on usual intake of meats and on meat preparation practices. Color photographs showing various doneness levels of hamburger, beefsteak, and bacon were included. Multivariate analysis was performed on data from 273 case subjects and 657 control subjects who completed the survey. RESULTS: A dose-response relationship was found between doneness levels of meat consumed and breast cancer risk. The adjusted odds ratios (ORs) for very well-done meat versus rare or medium-done meat were 1.54 (95% confidence interval [CI]=0.96-2.47) for hamburger, 2.21 (95% CI=1.30-3.77) for beef steak, and 1.64 (95% CI=0.92-2.93) for bacon. Women who consumed these three meats consistently very well done had a 4.62 times higher risk (95% CI=1.36-15.70) than that of women who consumed the meats rare or medium done. Risk of breast cancer was also elevated with increasing intake of well-done to very well-done meat. CONCLUSIONS: Consumption of well-done meats and, thus, exposures to heterocyclic amines (or other compounds) formed during high-temperature cooking may play an important role in the risk of breast cancer.

Isolation of Mycoplasma hominis from a brain abscess.

Mycoplasma hominis is a commensal in the genital tract of women and has been associated with urogenital and extragenital infections. However, central nervous system infections with this organism in adults are very rare. Here we describe the recovery of M. hominis from a brain abscess associated with a postpartum infection. Seroconversion to the isolated strain was detected by both a metabolic inhibition test and an immunoblotting assay. This case demonstrates the pathogenic potential of M. hominis and the need for rapid recognition of the organism so that appropriate chemotherapeutic intervention can occur.