The association between slow-wave sleep and choroid plexus calcifications in older adults. Results from the sleep disorders substudy of the Atahualpa Project cohort.

OBJECTIVE: It has been suggested that choroid plexus calcifications (CPC) may be associated with glymphatic system dysfunction and with disturbed slow-wave (N3) sleep. If this is the case, volumetric analysis of CPC could be used to estimate the functional ability of the glymphatic system. However, data on this association is limited. This study aims to assess the association between percentages of N3 sleep - used as a putative marker of glymphatic system activity - and the volume of CPC in older adults. PATIENTS AND METHODS: Community-dwelling individuals aged ≥60 years enrolled in the Atahualpa Project Cohort received head CTs (for automated determinations of CPC volume) and a single-night polysomnography (PSG) for quantification of N3 sleep percentages. Multivariate linear regression and non-parametric models were fitted to assess the association between these variables. RESULTS: A total of 125 older adults (median age: 65 years; 32 % males) were included. The mean percentage of N3 sleep was 12.4±9.1 %, and the mean volume of CPC was 655±345.3 µL. Non-parametric locally weighted scatterplot smoothing showed that the volume of CPC increased as the percentage of N3 sleep increased, but only when N3 sleep is reduced (up to 12 % of total sleep time). The significance disappeared when PSG parameters were included in the model as well as in participants with normal N3 sleep percentages. CONCLUSIONS: Study results suggest that in the presence of severe reductions in N3 sleep, increased CPC volume may be a manifestation of choroid plexus compensation or adaptation, and not necessarily dysfunction.

Binge drinking and progression of white matter hyperintensities of presumed vascular origin in older men.

BACKGROUND: Information on trajectories of diffuse subcortical brain damage of vascular origin associated with binge drinking in older adults is limited. We sought to evaluate the impact of this drinking pattern on the progression of white matter hyperintensities (WMH) of presumed vascular origin in individuals aged ≥60 years taken from the community. METHODS: Following a longitudinal prospective design, participants of the Atahualpa Project Cohort received interviews to assess patterns of alcohol intake as well as baseline and follow-up brain MRIs. Only men were included because alcohol consumption in women is negligible and tend not to engage in binge drinking in our studied population. Poisson regression models were fitted to assess the incidence rate ratio of WMH progression by patterns of alcohol use (binge drinking or not), after adjusting for demographics, level of education and cardiovascular risk factors. RESULTS: The study included 114 men aged ≥60 years (mean age: 65.1±5.4 years). Thirty-seven participants (32%) reported binge drinking for more than 30 years. Follow-up MRIs revealed WMH progression in 45 participants (39%) after a median of 7.2 years. In unadjusted analysis, the risk of WMH progression among individuals with binge drinking was 2.08 (95% C.I.: 1.16-3.73). After adjustment for age, education level and vascular risk factors, participants with this drinking pattern were 2.75 times (95% C.I.: 1.42-5.30) more likely to have WMH progression than those who did not. CONCLUSIONS: Study results show an independent association between binge drinking and WMH progression in community-dwelling older men.

Does Escalating Violence and Associated Fear of Crime Worsen Psychological Well-Being in Community Dwellers Living in a Rural Setting? Results From the Atahualpa Project Cohort.

BACKGROUND: Escalating street violence and criminal homicides have an adverse impact on psychological well-being. However, these consequences have been difficult to evaluate. Using a recently validated scale, we aimed to assess the impact of fear of crime on the psychological status of middle-aged and older adults living in a rural setting afflicted by endemic violence. METHODS: Participants were selected from Atahualpa residents included in previous studies targeting psychological distress in the population. A validated scale was used to objectively quantify fear of crime in participants. Differences in symptoms of depression and anxiety between baseline and follow-up were used as distinct dependent variables and the continuous score of the fear of crime scale was used as the independent variable. Linear regression models were fitted to assess the association between the exposure and the outcomes, after adjusting for relevant confounders. RESULTS: A total of 653 participants (mean age = 53.2 ± 11.5 years; 57% women) completed the requested tests. We found a 13% increase in symptoms of depression and anxiety during the peak of violence in the village compared with previous years. Linear regression models showed a significant association between the total score on the fear of crime questionnaire and worsening symptoms of depression (ß = .24; 95% CI = 0.14-0.35) and anxiety (ß = .31; 95% CI = 0.24-0.37), after adjustment for relevant confounders. CONCLUSIONS: This study shows a significant aggravating effect of fear of crime on pre-existing symptoms of depression and anxiety and a deleterious effect of these conditions on overall well-being.

Large (≥3-Millimeter) Parenchymal Brain Calcified Cysticerci Are More Often Associated with Hippocampal Atrophy than Smaller Ones in Seizure-Free Individuals with a Single Lesion.

Calcified cysticerci are often associated with hippocampal atrophy (HA). While most studies suggest that repetitive seizures cause HA in these patients, others have demonstrated that HA may also occur in persons without epilepsy. Little is known about mechanisms triggering HA in seizure-free individuals with calcified cysticerci. Here, we aimed to assess whether the size of the calcification is associated with HA. Using a population-based design, we selected apparently seizure-free individuals with a single calcified cysticercus in whom interictal paroxysmal activity and other causes of HA have been discarded. A total of 55 individuals (mean age, 58.3 ± 13 years, 62% women) fulfilled inclusion criteria. Unadjusted and multivariate models were fitted to assess the association between the size of the calcification dichotomized into <3 mm and ≥3 mm (exposure) and the presence of HA (outcome). Sixteen participants (29%) had HA, which was asymmetric in eight (50%) cases. Hippocampal atrophy was noted in 11/20 (55%) participants with large calcifications and in 5/35 (14%) with small calcifications (P = 0.001). A multivariate logistic regression model showed a significant association between the presence of large calcifications and HA, after adjustment for relevant confounders (odds ratio: 7.78; 95% CI: 1.72-35.1). Participants with calcifications ≥3 mm in diameter were 7.8 times more likely to have HA than those with smaller ones. Study results open avenues of research for the use of agents to prevent HA progression.

On the association between dietary oily fish intake and bone mineral density in frequent fish consumers of Amerindian ancestry. The three villages study.

Reports addressing the effects of oily fish intake on bone health are inconsistent. This study shows that consumption of ≥ 5.2 oily fish servings/week (728 g) is associated with lower prevalence of osteopenia/osteoporosis in elderly women of Amerindian ancestry. Results suggest a beneficial effect of oily fish intake in this population. OBJECTIVES: Oily fish is a major dietary source of omega-3 polyunsaturated fatty acids and other nutrients that may have a positive effect on bone health. However, this association is inconsistent and seems to be more evident in certain ethnic groups. We aimed to assess the association between oily fish intake and bone mineral density (BMD) in frequent fish consumers of Amerindian ancestry living in rural Ecuador. METHODS: This study included 399 individuals aged ≥ 60 years living in three neighboring rural villages of coastal Ecuador. Dietary oily fish intake was quantified systematically using validated surveys and BMD was determined by dual-energy x-ray absorptiometry. Ordinal logistic regression models, adjusted for demographics and cardiovascular risk factors, were fitted to assess the independent association between oily fish intake and bone health. RESULTS: Participants had a mean age of 68.8 ± 6.8 years, and 58% were women. The mean intake of oily fish was 8.5 ± 4.7 servings/week, with 308 (77%) reporting high fish intake (≥ 5.2 servings/week [728 g]). Ninety-four (24%) participants had normal BMD T-scores, 149 (37%) had osteopenia, and 156 (39%) had osteoporosis. Ordinal logistic regression models showed no association between high fish intake and bone health in the total population. When men and women were analyzed separately, the association became significant for women only in both unadjusted (OR: 2.52; 95% C.I.: 1.22 - 5.23) and fully-adjusted models (OR: 2.23; 95% C.I.: 1.03 - 4.81). CONCLUSION: Consumption of ≥ 5.2 oily fish servings/week is associated with lower prevalence of osteopenia and osteoporosis in elderly women of Amerindian ancestry.

Choroid plexus calcifications are not associated with putative markers of glymphatic dysfunction: A population study in middle-aged and older adults.

BACKGROUND AND PURPOSE: Recent studies have suggested an association between dysfunction of the choroid plexus and the glymphatic system. However, information is inconclusive. Following a population-based study design, we aimed to assess the association between choroid plexus calcifications (CPCs)-as a surrogate of choroid plexus dysfunction-and severity and progression of putative markers of glymphatic dysfunction, including white matter hyperintensities (WMH) of presumed vascular origin and abnormally enlarged basal ganglia perivascular spaces (BG-PVS). METHODS: This study recruited community-dwellers aged ≥40 years living in neighboring Ecuadorian villages. Participants who had baseline head CTs and brain MRIs were included in cross-sectional analyses and those who additional had follow-up MRIs (after a mean of 6.4 ± 1.5 years) were included in longitudinal analyses. Logistic and Poisson regression models, adjusted for demographics and cardiovascular risk factors, were fitted to assess associations between CPCs and WMH and enlarged BG-PVS severity and progression. RESULTS: A total of 590 individuals were included in the cross-sectional component of the study, and 215 in the longitudinal component. At baseline, 25% of participants had moderate-to-severe WMH and 27% had abnormally enlarged BG-PVS. At follow-up, 36% and 20% of participants had WMH and enlarged BG-PVS progression, respectively. Logistic regression models showed no significant differences between CPCs volumes stratified in quartiles and severity of WMH and enlarged BG-PVS. Poisson regression models showed no association between the exposure and WMH and enlarged BG-PVS progression. Baseline age remained significant in these models. CONCLUSIONS: Choroid plexus calcifications are not associated with putative markers of glymphatic system dysfunction.

Dietary oily fish intake is inversely associated with moderate-to-severe intracranial artery stenosis in older adults of indigenous Ecuadorian ancestry.

BACKGROUND AND AIMS: Information on the association between dietary oily fish intake and intracranial atherosclerosis is limited and contradictory. Inconsistencies might be in part related to heterogeneous designs and differences in race/ethnicity of study populations. We aim to assess whether oily fish intake is inversely associated with intracranial artery stenosis (ICAS) in frequent fish consumers of indigenous ancestry living in coastal Ecuador. METHODS: The study included 384 participants aged ≥60 years enrolled in the Atahualpa Project Cohort. Dietary oily fish intake was quantified systematically via validated surveys and all participants received a time-of-flight MRA of intracranial vessels. Poisson regression models, adjusted for demographics, level of education, traditional risk factors and severe tooth loss, were fitted to assess the association between amounts of oily fish intake and the number of intracranial arteries with moderate-to-severe (≥50 %) stenosis. RESULTS: Participants had a mean age of 67.7 ± 7 years, and 56 % were women. The mean oily fish intake was 8.9 ± 5.2 servings/week; 283 (74 %) participants consumed ≥5.2 servings/week (2nd to 4th quartiles of fish intake). Forty-three (11 %) participants had at least one major intracranial artery with moderate-to-severe stenosis. Both univariate and multivariate models showed a significant inverse association between consumption of oily fish in the 2nd to 4th quartiles and ≥50 % stenosis in at least one artery (ß: 0.46; 95 % C.I.: 0.27-077, and ß: 0.52; 95 % C.I.: 0.30-0.90, respectively). CONCLUSIONS: Consumption of more than five oily fish servings/week is associated with lower prevalence of moderate-to-severe ICAS in indigenous Ecuadorians.

The Impact of Biological and Social Factors on Mortality in Older Adults Living in Rural Communities.

BACKGROUND: Information on factors that increase mortality in remote settings is limited. This study aims to estimate the independent and joint role of several factors on mortality risk among older adults living in rural Ecuador. METHODS: Participants were selected from community-dwelling older adults who were included in previous studies targeting mortality risk factors in the study population. Generalized structural equation modeling (GSEM) was utilized to evaluate prior causal assumptions, to redraw causal links, and to introduce latent variables that may help to explain how the independently significant variables are associated with mortality. RESULTS: The study included 590 individuals (mean age: 67.9 ± 7.3 years; 57% women), followed for a median of 8.2 years. Mortality rate was 3.4 per 100 person-years. Prior work on separate multivariate Poisson and Cox models was used to build a tentative causal construct. A GSEM containing all variables showed that age, symptoms of depression, high social risk, high fasting glucose, a history of overt stroke, and neck circumference were directly associated with mortality. Two latent variables were introduced, 1 representing the impact of biological factors and another, the impact of social factors on mortality. The social variable significantly influenced the biological variable which carried most of the direct effect on mortality. CONCLUSIONS: Several factors contributed to mortality risk in the study population, the most significant being biological factors which are highly influenced by social factors. High social risk interact with biological variables and play an important role in mortality risk.

Neck circumference as a predictor of all-cause mortality in middle-aged and older adults in rural Ecuador.

BACKGROUND: Neck circumference (NC) has been associated with mortality secondary to cardiovascular diseases and other conditions. However, information on this association in the population at large is limited. We aimed to assess this association in community dwellers living in rural Ecuador. METHODS: Individuals aged ≥40 y who were enrolled in the population-based Three Villages Study cohort were prospectively followed to estimate mortality risk according to baseline measurements of NC, after adjusting for relevant confounders. RESULTS: Analysis included 1521 individuals followed for a mean of 6.4±3.4 y. Mean NC was 36.2±3.7 cm, with 509 (33%) individuals allocated to the first (25-34 cm), 319 (21%) to the second (36-37 cm), 417 (27%) to the third (37-39 cm) and 276 (18%) to the fourth (40-50 cm) quartile. A total of 211 (14%) individuals died during the follow-up. Overall, the crude mortality rate was 2.3 per 100 person-years, which increased to 5.63 for those in the fourth NC quartile. An adjusted Cox-proportional hazards model showed that individuals in the fourth quartile of NC had higher mortality risk compared with the first quartile (HR: 2.98; 95% CI 1.77 to 5.02). CONCLUSION: Larger NC increases mortality risk in middle-aged and older adults of indigenous ancestry living in rural Ecuador.

Cognitive performance and all-cause mortality in community dwellers of Amerindian ancestry living in rural Ecuador: A population-based, longitudinal prospective study.

OBJECTIVE: There is limited information on mortality risk in individuals with cognitive impairment living in rural Latin America. In this study, we assess the association between cognitive impairment and all-cause mortality in adults of Amerindian ancestry living in rural Ecuador. PATIENTS AND METHODS: Middle-aged and older adults enrolled in the population-based Three Villages Study cohort were followed prospectively in order to estimate mortality risk according to their baseline cognitive performance as determined by the Montreal Cognitive Assessment (MoCA). Results were adjusted for demographics, level of education, traditional cardiovascular risk factors, symptoms of depression, severe tooth loss, and oily fish intake (factors previously associated with mortality in the study population). RESULTS: Analysis included 1022 individuals followed for an average of 7.8 ± 3.4 years. Mean MoCA score was 21.2 ± 5.4 points (median: 22 points), with 334 (32.7%) individuals showing cognitive impairment, as evidenced by a MoCA score ≤ 19 points (the cutoff for poor cognitive performance based on previous studies in the same population). A total of 150 (14.7%) individuals died during the follow-up. Crude mortality rate was 2.87 per 100 person-years (95% C.I.: 2.08 - 3.96). For individuals with normal cognition, the mortality rate was 1.21 (95% C.I.: 0.92 - 1.50) while for those with cognitive impairment the rate increased to 3.48 (95% C.I.: 2.73 - 4.23). A multivariate Cox-proportional hazards model, confirmed that individuals with cognitive impairment had a significantly higher mortality risk than those without cognitive impairment (HR: 1.52; 95% C.I.: 1.05 - 2.18). CONCLUSIONS: Cognitive impairment is associated with mortality in the study population.

Poor sleep quality increases mortality risk: A population-based longitudinal prospective study in community-dwelling middle-aged and older adults.

OBJECTIVES: To assess the association between sleep quality and all-cause mortality in community-dwelling adults living in rural Ecuador. METHODS: Individuals aged ≥40years enrolled in the prospective population-based Three Villages Study cohort were included. Sleep quality was assessed by means of the Pittsburgh Sleep Quality Index. Study participants were evaluated at baseline and at every annual door-to-door survey until they remained enrolled in the study. Mixed models Poisson regression for repeated Pittsburgh Sleep Quality Index determinations and multivariate Cox-proportional hazards models were fitted to estimate mortality risk according to sleep quality. RESULTS: Analysis included 1494 individuals (mean age: 56.6 ± 12.5years; 56% women) followed for a median of 6.3 ± 3.3years. At baseline, 978 (65%) individuals had good sleep quality and 516 (35%) had poor sleep quality. The effects of Pittsburgh Sleep Quality Index scores changing over time on mortality was confounded by the impact of the SARS-CoV-2 pandemic on both. One hundred ninety-five individuals (13%) died during the follow-up, resulting in a crude mortality rate of 1.58 per 100 person years (95% C.I.: 1.27-1.88) for individuals with good sleep quality, and 3.18 (95% C.I.: 2.53-3.82) for those with poor sleep quality at baseline. A multivariate Cox-proportional hazards model showed that individuals with poor sleep quality at baseline were 1.38 times (95% C.I.: 1.02-1.85) more likely to die compared to those with good sleep quality; in this model, increased age, poor physical activity, and high fasting glucose remained significant. CONCLUSIONS: Poor sleep quality is associated with increased mortality risk among middle-aged and older adults.

Incompleteness of the Circle of Willis and progression of white matter hyperintensities of presumed vascular origin. A longitudinal prospective study in community-dwelling older adults.

BACKGROUND: Evidence on the association between anatomical variants of the circle of Willis (CoW) and severity of white matter hyperintensities (WMH) of presumed vascular origin is inconclusive, and no study has evaluated the role of incompleteness of CoW on WMH progression in the follow-up. This study aims to assess the impact of incomplete configurations of the CoW on WMH progression in community-dwelling older adults. METHODS: Following a prospective longitudinal study design, individuals aged ≥60 years enrolled in the Atahualpa Project Cohort from 2012 to 2019 were invited to receive baseline brain MRI and MRA of intracranial vessels, and those who also had brain MRIs at the end of the study (May 2021) were included in the analysis. Poisson regression models, adjusted for demographics and cardiovascular risk factors, were fitted to assess the incidence rate ratio (IRR) of WMH progression according to incompleteness of CoW. RESULTS: This study included 254 individuals (mean age: 65.4±5.9 years; 55% women). An incomplete CoW was detected in 99 (39%) subjects. Follow-up MRIs showed WMH progression in 103 (41%) individuals after a median follow-up of 6.5±1.4 years. WMH progression was observed in 58/155 subjects with complete and in 45/99 with incomplete CoW (37% versus 45%; p=0.203). There was no association between incomplete CoW and WMH progression in a multivariate Poisson regression model (IRR: 1.21; 95% C.I.: 0.81 - 1.82). CONCLUSIONS: Study results show that incompleteness of CoW is not involved in WMH progression.

Systemic immune-inflammation index and progression of white matter hyperintensities of presumed vascular origin. A longitudinal population study in community-dwelling older adults living in rural Ecuador.

BACKGROUND: Information on the association between the systemic immune-inflammation index (SII) and white matter hyperintensities (WMH) of presumed vascular origin is confined to cross-sectional studies. We sought to evaluate the impact of SII on WMH progression in community-dwelling older adults. METHODS: Following a longitudinal prospective study design, participants of a population-based cohort received baseline blood tests to calculate the SII (platelets x neutrophils / lymphocytes x 109 L) together with clinical interviews and brain MRIs. Participants with follow-up brain MRI were included in the analysis. Poisson regression models adjusted for demographics and cardiovascular risk factors were fitted to assess the incidence rate ratio of WMH progression by levels of the SII. RESULTS: Across 246 study participants (mean age: 65.5 ± 5.9 years; 55% women), the mean SII was 434.7 ± 193.8 × 109 L, and WMH progression was found in 101 (41%) individuals after a mean of 7.3 ± 1.5 years. A multivariate Poisson regression model showed increased WMH progression rate among individuals in the fourth quartile of the SII compared with those in the first quartile (IRR: 1.87; 95% C.I.: 1.02-3.41). CONCLUSIONS: Study results provided novel evidence of an independent association between the SII and WMH progression. The SII may be able to identify individuals at high risk of WMH progression.

Severe tooth loss and mortality risk: a population-based, longitudinal prospective study in a rural setting.

BACKGROUND: Information on the relationship between tooth loss and mortality among individuals living in rural settings is limited. METHODS: In this prospective cohort study, Atahualpa residents ≥40 y of age (n=933) were followed for a mean of 7.3±3.2 y to estimate mortality risk according to whether they had severe tooth loss (<10 remaining teeth). RESULTS: Overall, 151 individuals (16%) died, resulting in a crude mortality rate of 2.35 per 100 person-years of follow-up. Individuals with severe tooth loss were more likely to die (73/276) compared with those with mild-moderate tooth loss (78/657), after adjusting for relevant covariates (hazard ratio 1.45 [95% confidence interval 1.02 to 2.04]). CONCLUSIONS: Severe tooth loss is associated with increased mortality in remote communities.

High social risk and mortality. A prospective study in community-dwelling older adults living in a rural Ecuadorian village.

High social risk has been associated with mortality, but information on this relationship in remote rural communities is limited. Using the social determinants of health (SDH) specified in the Gijon's social-familial evaluation scale (SFES), we aimed to assess mortality risk according to levels of social risk in community-dwelling older adults living in rural Ecuador. Following a longitudinal population-based design, this study prospectively followed 457 individuals for an average of 8.2 ± 2.6 years. A total of 115 (25.2 %) individuals died during the study years. The mean Gijon's SFES score was 9.4 ± 2.8 points among survivors versus 12.3 ± 4 points among those who died (p < 0.001). Separate models using individual SDH components as exposures showed that deficits in family situation, social relationships and support networks were significantly associated with mortality, whereas economic status and housing factors were not. A Cox-proportional hazard model, with the Gijon's SFES score stratified in tertiles, showed a more than 5-fold increase in mortality among individuals in the third tertile compared with those in first and second tertiles, after adjusting for relevant covariates (HR: 5.36; 95 % C.I.: 3.09 - 9.32). Study results indicate an important contribution of high social risk to mortality, and may help to identify potential interventional targets that are focused on encouraging social interactions, and that may reduce mortality in older adults living in remote settings.

Dietary oily fish intake reduces the risk of all-cause mortality in frequent fish consumers of Amerindian ancestry living in coastal Ecuador: the Atahualpa project.

PURPOSE: To assess the relationship between dietary oily fish intake and all-cause mortality in a population of frequent fish consumers of Amerindian ancestry living in rural Ecuador. METHODS: Individuals aged ≥ 40 years enrolled in the prospective population-based Atahualpa Project cohort received annual questionnaires to estimate their dietary oily fish intake. Only fish served broiled or cooked in the soup were included for analysis. Poisson regression and Cox-proportional hazards models adjusted for demographics, education level and cardiovascular risk factors were obtained to estimate mortality risk according to the amount of oily fish intake stratified in tertiles. RESULTS: Analysis included 909 individuals (mean age: 55.1 ± 12.8 years) followed by a median of 7.5 ± 3 years. Mean oily fish intake was 9.4 ± 5.7 servings per week. A total of 142 (16%) individuals died during the follow-up. The mortality rate for individuals in the first tertile de oily fish intake (0.0-6.29 servings) was 2.87 per 100 person-years, which decreased to 1.78 for those in the third tertile (10.59-35.0 servings). An adjusted Cox-proportional hazards model showed that individuals allocated to the second (HR 0.61; 95% CI 0.41-0.92) and third (HR 0.60; 95% CI 0.40-0.91) tertiles of dietary oily fish intake had significantly lower mortality risk than those in the first tertile. CONCLUSION: Sustained oily fish intake of more than six servings per week reduces mortality risk in middle-aged and older adults of Amerindian ancestry.