Behavioral and dysexecutive variant of Alzheimer's disease: Insights from structural and molecular imaging studies.

Frontal variant Alzheimer's disease (AD) manifests with either behavioral or dysexecutive syndromes. Recent efforts to gain a deeper understanding of this phenotype have led to a re-conceptualization of frontal AD. Behavioral (bAD) and dysexecutive (dAD) phenotypes could be considered subtypes, as suggested by both clinical and neuroimaging studies. In this review, we focused on imaging studies to highlight specific brain patterns in these two uncommon clinical AD phenotypes. Although studies did not compare directly these two variants, a common epicenter located in the frontal cortex could be inferred. On the contrary, 18F-FDG-PET findings suggested differing metabolic patterns, with bAD showing specific involvement of frontal regions and dAD exhibiting widespread alterations. Structural MRI findings confirmed this pattern, suggesting that degeneration might involve neural circuits associated with behavioral control in bAD and attentional networks in dAD. Furthermore, molecular imaging has identified different neocortical tau distribution in bAD and dAD patients compared to typical AD patients, although the distribution is remarkably heterogeneous. In contrast, Aß deposition patterns are less differentiated between these atypical variants and typical AD. Although preliminary, these findings underscore the complexity of AD frontal phenotypes and suggest that they represent distinct entities. Further research is essential to refine our understanding of the pathophysiological mechanisms in frontal AD.

Characterizing the Individuals Who Regain or Maintain Walking Ability after a Hip Fracture: Insights Into Physical Resilience.

OBJECTIVES: Maintaining walking ability is key to healthy aging. Hip fractures often lead to declined walking ability. This study investigated characteristics of individuals who regained walking ability after a hip fracture, an expression of physical resilience. DESIGN: Register-based cohort study. SETTING AND PARTICIPANTS: A total of 55,467 Swedish residents aged ≥60 years with a first hip fracture (71% women, mean age = 82.3 ± 8) included in the Swedish Hip Fracture Register. METHODS: Information about diseases, medications, and socioeconomic (SES) factors came from registers. Individuals were classified by prefracture walking ability (independent or assisted walking) and whether their walking ability 4 months post-fracture was maintained (physical resilience or nonresilience). Cluster analyses were conducted among individuals who maintained their walking ability to assess different physical resilience profiles. RESULTS: At baseline, 38,493 individuals walked independently (69%), and 16,982 were assisted walkers. Half of the independent walkers maintained their walking ability 4 months post-fracture. Among them, 3 clusters were identified: a "Low SES, Low Disease" cluster (n = 8580, mean age 81.1 ± 7.5); a "High SES, Low Disease" cluster (n = 7778, mean age 76.7 ± 7.4); and a third "High SES, High Disease" cluster (n = 4320, mean age 77.7 ± 7.4). Sixty percent of the pre-assisted walkers maintained their level of assisted walking ability. Also among them, 3 clusters were identified: a "Low SES-Independent Living" cluster (n = 3077, mean age 85.5 ± 7.1); a second "Care Home" cluster (n = 2912, mean age 87.0 ± 6.5) with a high proportion with dementia diagnosis; and a last "High SES" cluster (n = 4044, mean age 83.0 ± 7.0) with the largest proportion of men. CONCLUSIONS AND IMPLICATIONS: Physical resilience is not characterized by one typical healthy profile, and it is possible to regain walking ability after a hip fracture despite unfavorable prerequisites in 1 domain. A favorable status in one domain may compensate for an unfavorable status in another, for example, a high disease burden in combination with high SES.

A short length of hospital stay is not associated with risk of readmission among hip fracture patients - a Swedish national register-based cohort study.

BACKGROUND: Hospital length of stay (LoS) after a hip fracture likely mirrors health status; however, a too short hospitalization might increase the risk of readmission. In this national register-based study, we investigated the association between LoS after a hip fracture and the risk of readmissions. METHODS: 73,551 patients with a first hip fracture between 2012 and 2019 were followed for 4 months after discharge. LoS was categorized by cubic splines and the association with readmissions was analyzed with Cox regression models. RESULTS: The mean LoS was 11 ± 6 days and 25% of the study population had at least one readmission. Compared to the mean LoS of 9-12 days, there was a 18% decreased risk of readmission for LoS of 2-4 days (HR 0.82 [95% CI 0.77-0.87]) and 13% decrease for 5-8 days (HR 0.87 [95% CI 0.83-0.91]), when adjusting for sex, age, walking ability, ASA score, CCI, complications during hospitalization and living arrangements. For longer LoS, risk of readmission increased (13-23 days: HR 1.09 [95% CI 1.05-1.13] and 24 + days: HR 1.19 [95% CI 1.11-1.28]). The results were robust across sex, age, and living arrangements. The most common specific reasons for readmission were trauma/injury, cardiovascular and complications, and the proportions did not differ considerably between short and long LoS-categories. CONCLUSIONS: While a long LoS can be explained by the care need of the patient, a short LoS - compared to the average stay - does not increase the risk of readmission regardless of health status and hospital complications in a Swedish setting.

Population frailty trends by education and income levels over a period of 30 years: findings from Swedish registry data.

BACKGROUND: Frailty is an age-related health condition affecting an estimated 18% of older adults in Europe and past evidence has shown a relationship between socioeconomic factors and frailty. We examined population frailty trends and the association between frailty and 5-year mortality by education tertiles and income quartiles at ages 75, 85 and 95 in Swedish registry data. METHODS: All Swedish residents born in 1895-1945 and in the Total Population Register from 1990 to 2020 were included. Frailty was assessed with the Hospital Frailty Risk Score (HFRS), which sums 109 weighted International Classification of Diseases (ICD codes), collected from the National Patient Register. RESULTS: Regardless of education and income, frailty increased over time, though the association between frailty and 5-year mortality remained stable. Particularly in earlier birth cohorts, although the highest education and income levels had the highest mean HFRS scores, the lowest education and income levels accounted for greater proportions among the frail. These trends varied slightly by sex and age. Men and women had similar levels of frailty, but frailty was more strongly associated with mortality among men. CONCLUSION: Over time, education and income levels were more equally represented among the frail population in more recent years. More equitable distribution over time may suggest improvement in health disparities, though more work is needed. The overall increase in frailty and unchanged association with mortality indicates that additional research is needed to better understand how to best support the growing ageing population. This would then support the long-term viability of the healthcare system.

Risk of All-Cause Dementia, Alzheimer Disease, and Vascular Dementia in Breast Cancer Survivors: A Longitudinal Register-Based Study.

Background and Objectives: Now more than two-thirds of cancer survivors are aged 65 years or older, but evidence about their long-term health is thin. Cancer and its treatments have been linked to accelerated aging, so there is a concern that aging cancer survivors have an increased risk of age-related diseases, including dementia. Methods: We examined the risk of dementia among 5-year breast cancer survivors using a matched cohort study design. We included breast cancer survivors aged 50 years and older at diagnosis (n = 26,741) and cancer-free comparison participants (n = 249,540). Women eligible for inclusion in the study were those born 1935-1975 and registered in the Swedish Total Population Register between January 1, 1991, and December 31, 2015. We defined breast cancer survivors as women with an initial breast cancer diagnosis between 1991 and 2005 who survived 5 or more years after their first diagnosis. We assessed all-cause dementia, Alzheimer disease (AD), and vascular dementia (VaD) using International Classification of Diseases codes. Survival analyses were conducted using age-adjusted subdistribution hazard models accounting for competing risk of death. Results: We did not observe an association between breast cancer survivorship and risk of all-cause dementia, AD, or VaD. However, in models stratified by age at cancer diagnosis, women diagnosed with cancer after age 65 years had a higher risk of all-cause dementia (subdistribution hazard ratio [SHR] = 1.30, 95% CI 1.07-1.58), AD (SHR = 1.35, 95% CI 1.05-1.75), and VaD (SHR = 1.64, 95% CI 1.11-2.43) in models adjusted for age, education, and country of origin. Discussion: Older breast cancer survivors who survive cancer have a higher risk for dementia than their peers without a cancer diagnosis, in contrast to earlier studies showing that prevalent or incident cancer is associated with a lower risk of dementia. With the older adult population growing rapidly and because cancer and dementia are 2 of the most common and debilitating diseases among older adults, it is critical that we understand the link between the 2.

Subjective Sleep Quality as it Relates to Cognitive and Physical Function in Spinal Muscular Atrophy Patients.

Sleep quality and its association with cognition has been widely studied in some neurodegenerative diseases, but less is known about this association in spinal muscular atrophy (SMA). In adult SMA (n = 21) patients and age-matched controls (n = 23), we assessed subjectively measured sleep quality and daytime somnolence. Cognition was assessed with a multi-domain neuropsychological battery. Further, we investigated the association between clinical functional scores and sleep questionnaire scores. Among SMA patients, better motor and limb function was associated with better subjective sleep quality (p's< 0.05). Clinicians should consider sleep quality in patient care and future studies are needed to better understand these relationships.

Time trends in atrial fibrillation-related stroke during 2001-2020 in Sweden: a nationwide, observational study.

Background: Great efforts have been made to improve stroke prevention in atrial fibrillation (AF) patients. Meanwhile, incidence of AF is increasing, which may affect the share of AF-related stroke on all strokes. We aimed to examine the temporal trends in the incidence of AF-related ischemic stroke between 2001 and 2020, if it varied by use of novel oral anticoagulant drugs (NOAC), and if the relative risk of ischemic stroke associated with AF changed over time. Methods: Data from the total Swedish population aged ≥70 years during the period 2001-2020 were used. Annual incidence rate (IR) was calculated for overall and AF-related ischemic stroke which was defined as first-ever ischemic stroke with AF diagnosed up to 5 years before, on the same day, or within 2 months after the stroke event. Cox regression models were performed to examine if the hazard ratio (HR) between AF and stroke changed over time. Findings: While IR of ischemic strokes declined during 2001-2020, IR of AF-related ischemic stroke remained stable between 2001 and 2010 but showed a consistent decline between 2010 and 2020. The HR of ischemic stroke within 3 years from an AF diagnosis came down from 2.39 (95% confidence interval: 2.31-2.48) to 1.54 (1.48-1.61) over the study period, which was largely explained by a substantial increase in the use of NOAC among AF patients after 2012. Yet, by the end of 2020, 24% of all ischemic strokes had a preceding or concurrent AF diagnosis, which is slightly higher than in 2001. Interpretation: Even though both the absolute and relative risk of AF-related ischemic stroke declined over the past 20 years, every fourth ischemic stroke in 2020 still had a preceding or concurrent AF diagnosis. This represents a great potential for future gains in stroke prevention among AF patients. Funding: Swedish Research Council and Loo and Hans Osterman Foundation for Medical Research.

Association of common infections with cognitive performance in the Baltimore Epidemiologic Catchment Area study follow-up.

INTRODUCTION: Growing evidence suggests that some common infections are causally associated with cognitive impairment; however, less is known about the burden of multiple infections. METHODS: We investigated the cross-sectional association of positive antibody tests for herpes simplex virus, cytomegalovirus (CMV), Epstein-Barr virus (EBV), varicella zoster virus (VZV), and Toxoplasma gondii (TOX) with Mini-Mental State Examination (MMSE) and delayed verbal recall performance in 575 adults aged 41-97 from the Baltimore Epidemiologic Catchment Area Study. RESULTS: In multivariable-adjusted zero-inflated Poisson (ZIP) regression models, positive antibody tests for CMV (p = .011) and herpes simplex virus (p = .018) were individually associated with poorer MMSE performance (p = .011). A greater number of positive antibody tests among the five tested was associated with worse MMSE performance (p = .001). DISCUSSION: CMV, herpes simplex virus, and the global burden of multiple common infections were independently associated with poorer cognitive performance. Additional research that investigates whether the global burden of infection predicts cognitive decline and Alzheimer's disease biomarker changes is needed to confirm these findings.

How both positive and burdensome caregiver experiences are associated with care recipient cognitive performance: Evidence from the National Health and Aging Trends Study and National Study of Caregiving.

Introduction: Being an informal caregiver to a person with chronic disease, including persons living with dementia (PLWD), is a big role to take on and many caregivers experience both substantial burden and emotional reward related to caregiving. Care recipient factors (e.g., behavioral symptoms) are associated with caregiver experience. However, the relationship between caregiver and care recipient is bidirectional, so it is likely that caregiver factors impact the care recipient, though few studies have investigated this. Methods: In the 2017 round of the National Health and Aging Trends Study (NHATS) and National Study of Caregiving (NSOC), we studied 1,210 care dyads--170 PLWD dyads and 1,040 without dementia dyads. Care recipients completed immediate and delayed word list memory tasks, the Clock Drawing Test, and a self-rated memory rating, while caregivers were interviewed about their caregiving experiences using a 34-item questionnaire. Using principal component analysis, we created a caregiver experience score with three components-Practical Care Burden, Positive Care Experiences, and Emotional Care Burden. We then investigated the cross-sectional association between caregiver experience components and care recipient cognitive test performance using linear regression models adjusted for age, sex, education, race, and depressive and anxiety symptoms. Results: Among PLWD dyads, a higher caregiver Positive Care Experiences score was associated with better care recipient performance on the delayed word recall (B = 0.20, 95% CI 0.05, 0.36) and Clock Draw (B = 0.12, 95% CI 0.01, 0.24) tests while higher Emotional Care Burden score was associated with worse self-rated memory score (B = -0.19, 95% CI -0.39, -0.003). Among participants without dementia, higher Practical Care Burden score was associated with poorer care recipient performance on the immediate (B = -0.07, 95% CI -0.12, -0.01) and delayed (B = -0.10, 95% CI -0.16, -0.05) word recall tests. Discussion: These findings support the concept that caregiving is bidirectional within the dyad and that positive variables can positively impact both members of the dyad. This suggests that caregiving interventions should target the caregiver and recipient both individually and as a unit, with the goal of holistically improving outcomes for both.

Frailty Among Breast Cancer Survivors: Evidence From Swedish Population Data.

Incidence and survival of breast cancer, the most common cancer among women, have been increasing, leaving survivors at risk of aging-related health conditions. In this matched cohort study, we examined frailty risk with the Hospital Frailty Risk Score among breast cancer survivors (n = 34,900) and age-matched comparison subjects (n = 290,063). Women born in 1935-1975, registered in the Swedish Total Population Register (1991-2015), were eligible for inclusion. Survivors had a first breast cancer diagnosis in 1991-2005 and survived ≥5 years after initial diagnosis. Death date was determined by linkage to the National Cause of Death Registry (through 2015). Cancer survivorship was weakly associated with frailty (subdistribution hazard ratio (SHR) = 1.04, 95% confidence interval (CI): 1.00, 1.07). In age-stratified models, those diagnosed at younger ages (<50 years) had higher risk of frailty (SHR = 1.12, 95% CI: 1.00, 1.24) than those diagnosed at ages 50-65 (SHR = 1.03, 95% CI: 0.98, 1.07) or >65 (SHR = 1.09, 95% CI: 1.02, 1.17) years. Additionally, there was increased risk of frailty for diagnoses in 2000 or later (SHR = 1.15, 95% CI: 1.09, 1.21) compared with before 2000 (SHR = 0.97, 95% CI: 0.93, 1.17). This supports work from smaller samples showing that breast cancer survivors have increased frailty risk, particularly when diagnosed at younger ages.

Food Insufficiency, Supplemental Nutrition Assistance Program (SNAP) Status, and 9-Year Trajectory of Cognitive Function in Older Adults: The Longitudinal National Health and Aging Trends Study, 2012-2020.

BACKGROUND: Despite findings from cross-sectional studies, how food insecurity experience/Supplemental Nutrition Assistance Program (SNAP) status relates to cognitive decline over time has not been fully understood. OBJECTIVES: We aimed to investigate the longitudinal associations between food insecurity/SNAP status and cognitive function in older adults (≥65 y). METHODS: Longitudinal data from the National Health and Aging Trends Study 2012-2020 were analyzed (n = 4578, median follow-up years = 5 y). Participants reported food insecurity experience (5-item) and were classified as food sufficient (FS, no affirmative answer) and food insufficient (FI, any affirmative answer). The SNAP status was defined as SNAP participants, SNAP eligible nonparticipants (≤200% Federal Poverty Line, FPL), and SNAP ineligible nonparticipants (>200% FPL). Cognitive function was measured via validated tests in 3 domains, and the standardized domain-specific and combined cognitive function z-scores were calculated. Mixed-effect models with a random intercept were used to study how FI or SNAP status was associated with combined and domain-specific cognitive z-scores over time, adjusting for static and time-varying covariates. RESULTS: At baseline, 96.3% of the participants were FS and 3.7% were FI. In a subsample (n = 2832), 10.8% were SNAP participants, 30.7% were SNAP eligible nonparticipants, and 58.6% were SNAP ineligible nonparticipants. Compared with the FS group in the adjusted model (FI vs. FS), FI was associated with faster decline in the combined cognitive function scores [-0.043 (-0.055, -0.032) vs. -0.033 (-0.035, -0.031) z-scores per year, P-interaction = 0.064]. Cognitive decline rates (z-scores per year) in the combined score were similar in SNAP participants (ß = -0.030; 95% CI: -0.038, -0.022) and SNAP ineligible nonparticipants (ß = -0.028; 95% CI: -0.032, -0.024), both of which were slower than the rate in SNAP eligible nonparticipants (ß = -0.043; 95% CI: -0.048, -0.038; P-interaction < 0.0001). CONCLUSIONS: Food sufficiency and SNAP participation may be protective factors preventing accelerated cognitive decline in older adults.

The pollutome-connectome axis: a putative mechanism to explain pollution effects on neurodegeneration.

The study of pollutant effects is extremely important to address the epochal challenges we are facing, where world populations are increasingly moving from rural to urban centers, revolutionizing our world into an urban world. These transformations will exacerbate pollution, thus highlighting the necessity to unravel its effect on human health. Epidemiological studies have reported that pollution increases the risk of neurological diseases, with growing evidence on the risk of neurodegenerative disorders. Air pollution and water pollutants are the main chemicals driving this risk. These chemicals can promote inflammation, acting in synergy with genotype vulnerability. However, the biological underpinnings of this association are unknown. In this review, we focus on the link between pollution and brain network connectivity at the macro-scale level. We provide an updated overview of epidemiological findings and studies investigating brain network changes associated with pollution exposure, and discuss the mechanistic insights of pollution-induced brain changes through neural networks. We explain, in detail, the pollutome-connectome axis that might provide the functional substrate for pollution-induced processes leading to cognitive impairment and neurodegeneration. We describe this model within the framework of two pollutants, air pollution, a widely recognized threat, and polyfluoroalkyl substances, a large class of synthetic chemicals which are currently emerging as new neurotoxic source.

Comparison of two different frailty scales in the longitudinal Swedish Adoption/Twin Study of Aging (SATSA).

AIMS: Although up to 25% of older adults are frail, assessing frailty can be difficult, especially in registry data. This study evaluated the utility of a code-based frailty score in registry data by comparing it to a gold-standard frailty score to understand how frailty can be quantified in population data and perhaps better addressed in healthcare. METHODS: We compared the Hospital Frailty Risk Score (HFRS), a frailty measure based on 109 ICD codes, to a modified version of the Frailty Index (FI) Frailty Index (FI), a self-report frailty measure, and their associations with all-cause mortality both cross-sectionally and longitudinally (follow-up = 36 years) in a Swedish cohort study (n = 1368). RESULTS: The FI and HFRS were weakly correlated (rho = 0.11, p < 0.001). Twenty-two percent (n = 297) of participants were considered frail based on published cut-offs of either measure. Only 3% (n = 35) of participants were classified as frail by both measures; 4% (n = 60) of participants were considered frail by only the HFRS; and 15% (n = 202) of participants were considered frail based only on the FI. Frailty as measured by the HFRS showed greater variance and no clear increase or decrease with age, while frailty as measured by the FI increased steadily with age. In adjusted Cox proportional hazard models, baseline HFRS frailty (HR = 1.17, 95% CI 0.92, 1.49) was not statistically significantly associated with mortality, while FI frailty was (HR = 2.89, 95% CI 1.61, 2.23). These associations were modified by age and sex. CONCLUSIONS: The HFRS may not capture the full spectrum of frailty among community-dwelling individuals, particularly at younger ages, in Swedish registry data.

Trends in Frailty Between 1990 and 2020 in Sweden Among 75-, 85-, and 95-Year-Old Women and Men: A Nationwide Study from Sweden.

BACKGROUND: Aging is the primary risk factor for frailty, which is defined as an inability to respond to acute or chronic stressors. Individuals are living longer with greater multimorbidity, but there is a paucity of evidence examining frailty across birth cohorts and ages. METHODS: We investigated frailty prevalence and its association with mortality at ages 75, 85, and 95 in the 1895-1945 birth cohorts in Sweden with data from population registries. Frailty was assessed with the Hospital Frailty Risk Score (HFRS). RESULTS: We observed that frailty increased with increasing age and that it has become more common in more recent birth cohorts. At age 75, the percent frail in the Total Population Register increased from 1.1% to 4.6% from birth cohorts 1915-1945, corresponding to calendar years 1990-2020. At age 85, the percentage of frail increased from 3.5% to 11.5% from birth cohorts 1905-1935, and at age 95 from birth cohorts 1895-1925, from 4.7% to 18.7%. Our results show that the increase was primarily driven by an increase in the distribution of individuals with scores in the highest quartile of HFRS, while the bottom 3 quartiles remained relatively stable across birth cohorts. Women accounted for a greater distribution of the overall population and frail population, though these disparities decreased over time. Despite increasing levels of frailty, the relationship between frailty and mortality did not change over time, nor did it differ by sex. CONCLUSION: Increased frailty with improved survival points to a chronic condition that could be intervened upon.

Positive Aspects of Caregiving Are Associated With Lower Risk of Frailty and Sleep Disruption in the National Study of Caregiving.

Background and Objectives: Older adult caregivers have compounded risk for adverse health outcomes; however, evidence investigating the association between caregiving and frailty has been limited. In the National Study of Caregiving (NSOC), we examined the cross-sectional association between caregiving experiences and frailty and sleep disruption. Research Design and Methods: We included 621 caregivers aged 65 and older from the 2011 NSOC round. They completed a phone interview, including 36 items about caregiving. Using principal component analysis, we identified 3 caregiving components: general burden, positive emotions, and financial-led burden. Frailty was assessed via low energy, shrinking, weakness, reduced activity, and poor self-rated health. Sleep disruption was assessed with 2 questions regarding sleep interruption and trouble falling back asleep. Results: In models adjusted for age, sex, education, depression and anxiety symptoms, and medical conditions, positive emotions were associated with a reduced relative risk of frailty (relative risk [RR] = 0.94, 95% confidence interval [CI] 0.90, 0.99) while general burden (proportional odds ratio [POR] = 1.96, 95% CI 1.30, 2.93) and financial-led burden (POR = 1.94, 95% CI 1.22, 3.06) were associated with sleep interruption. Discussion and Implications: Caregiver burden was associated with increased frailty and sleep interruption. Positive emotions were associated with decreased frailty risk. Interventions aimed at reducing the burden and increasing positive emotions in caregivers may improve frailty outcomes.

Lipid levels in midlife and risk of atrial fibrillation over 3 decades-Experience from the Swedish AMORIS cohort: A cohort study.

BACKGROUND: The role of cholesterol levels in the development of atrial fibrillation (AF) is still controversial. In addition, whether and to what extent apolipoproteins are associated with the risk of AF is rarely studied. In this study, we aimed to investigate the association between blood lipid levels in midlife and subsequent risk of new-onset AF. METHODS AND FINDINGS: This population-based study included 65,136 individuals aged 45 to 60 years without overt cardiovascular diseases (CVDs) from the Swedish Apolipoprotein-Related Mortality Risk (AMORIS) cohort. Lipids were measured in 1985 to 1996, and individuals were followed until December 31, 2019 for incident AF (i.e., study outcome). Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using Cox regression, adjusting for age, sex, and socioeconomic status. Over a mean follow-up of 24.2 years (standard deviation 7.5, range 0.2 to 35.9), 13,871 (21.3%) incident AF cases occurred. Higher levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were statistically significantly associated with a lower risk of AF during the first 5 years of follow-up (HR = 0.61, 95% CI: 0.41 to 0.99, p = 0.013; HR = 0.64, 95% CI: 0.45 to 0.92, p = 0.016), but not thereafter (HR ranging from 0.94 [95% CI: 0.89 to 1.00, p = 0.038] to 0.96 [95% CI: 0.77 to 1.19, p > 0.05]). Lower levels of high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I (ApoA-I) and higher triglycerides (TG)/HDL-C ratio were statistically significantly associated with a higher risk of AF during the entire follow-up (HR ranging from 1.13 [95% CI: 1.07 to 1.19, p < 0.001] to 1.53 [95% CI: 1.12 to 2.00, p = 0.007]). Apolipoprotein B (ApoB)/ApoA-I ratio was not associated with AF risk. The observed associations were similar among those who developed incident heart failure (HF)/coronary heart disease (CHD) and those who did not. The main limitations of this study include lack of adjustments for lifestyle factors and high blood pressure leading to potential residual confounding. CONCLUSIONS: High TC and LDL-C in midlife was associated with a lower risk of AF, but this association was present only within 5 years from lipid measurement and not thereafter. On the contrary, low HDL-C and ApoA-I and high TG/HDL-C ratio were associated with an increased risk of AF over almost 35 years of follow-up. ApoB/ApoA-I ratio was not associated with AF risk.

Cognitive profiles and clinical factors in type III spinal muscular atrophy: a preliminary study.

Cognitive abilities are often affected in progressive neurodegenerative disorders, but there is a lack of understanding about whether spinal muscular atrophy (SMA) patients experience cognitive deficits and, if so, whether they are associated with clinical factors. A sample of 22 type III SMA patients and 22 healthy controls completed a comprehensive neuropsychological battery, including tests in memory, executive function, language, visuospatial, and global cognitive functioning. Clinical severity was assessed using the Hammersmith Functional Motor Scale, the Revised Upper Limb Module and the Six Minute Walk Test. SMA patients showed poorer performance in visuospatial abilities, executive functions and language as compared to healthy controls. In the SMA sample, patients with greater motor difficulties had lower performance in attention, but higher performance in measures of language, verbal fluency, and memory. In men, but not women, cognitive test performance was associated with motor functioning. Our findings showing cognitive changes in SMA type III may reflect the presence of intrinsic brain pathology and cognitive adaptation mechanisms following physical dysfunction, which may be mediated by other factors, such as sex.

Oral Manifestations and Maxillo-Facial Features in the Acromegalic Patient: A Literature Review.

Background: Acromegaly is a chronic disease caused by an abnormal secretion of growth hormone (GH) by a pituitary adenoma, resulting in an increased circulating concentration of insulin-like growth factor 1 (IGF-1). The main characteristics are a slow progression of signs and symptoms, with multisystemic involvement, leading to acral overgrowth, progressive somatic changes, and a complex range of comorbidities. Most of these comorbidities can be controlled with treatment. The literature reveals that the most evident and early signs are those related to soft tissue thickening and skeletal growth, especially in the head and neck region. Methods: The authors reviewed the available literature on the clinical oro-dental features of acromegaly, selecting articles from PubMed and Google Scholar. The aim of this review was to summarize all the reported clinical oro-dental features of acromegalic patients. Results: The most common facial dimorphisms involved the maxillo-facial district, with hypertrophy of the paranasal sinuses, thickening of the frontal bones, and protruding glabella, which may be associated with joint pain and clicks. Regarding the oro-dental signs, the most frequent are dental diastema (40-43%), mandibular overgrowth (22-24%), mandibular prognathism (20-22%), and macroglossia (54-58%). These signs of acromegaly can be significantly reduced with adequate treatment, which is more effective when initiated early. Conclusions: Increased awareness of acromegaly among dentists and maxillo-facial surgeons, along with the early identification of oro-facial changes, could lead to an earlier diagnosis and treatment, thereby improving patients' quality of life and prognosis.

The role of the dentist and orthodontist in recognizing oro-facial manifestations of acromegaly: a questionnaire-based study.

PURPOSE: Oro-facial manifestations of acromegaly are among the earliest signs of the disease and are reported by a significant number of patients at diagnosis. Despite this high prevalence of acromegaly oral manifestation, dentists do not play a pivotal role in acromegaly identification and diagnosis. The aim of our study was to evaluate the ability of dentists and orthodontists in the early recognition of the oro-facial manifestations of acromegaly. METHODS: A telematic questionnaire was administered to dentists and orthodontists. The questionnaire included photos with facial and oral-dental details and lateral teleradiography of acromegaly patients (ACRO). RESULTS: The study included 426 participants: 220 dentists and 206 orthodontists. Upon reviewing the photos, dentists most often observed mandibular prognathism and lips projection, while orthodontists also reported the impairment of relative soft tissue. Orthodontists, who usually use photos to document patients' oral-facial characteristics, paid more attention to oral-facial impairment than dentists. During dental assessment, 90% of the participants usually evaluated tongue size and appearance, diastemas presence, and signs of sleep impairment (mainly orthodontists). Orthodontists were also more able to identify sella turcica enlargement at teleradiography. A total of 10.8% of the participants had ACRO as patients and 11.3% referred at least one patient for acromegaly suspicion. CONCLUSION: The study highlighted dentists' strategic role in identifying ACRO. Increasing dentists' awareness about acromegaly clinical issues may improve early diagnosis, potentially resulting in an increased quality of life and decreased mortality among ACRO.