Periodontal Inflammation and Dysbiosis Relate to Microbial Changes in the Gut.

Periodontal disease (PerioD) is a chronic inflammatory disease of dysbiotic etiology. Animal models and few human data showed a relationship between oral bacteria and gut dysbiosis. However, the effect of periodontal inflammation and subgingival dysbiosis on the gut is unknown. We hypothesized that periodontal inflammation and its associated subgingival dysbiosis contribute to gut dysbiosis even in subjects free of known gut disorders. We evaluated and compared elderly subjects with Low and High periodontal inflammation (assessed by Periodontal Inflamed Surface Area (PISA)) for stool and subgingival derived bacteria (assayed by 16S rRNA sequencing). The associations between PISA/subgingival dysbiosis and gut dysbiosis and bacteria known to produce short-chain fatty acid (SCFA) were assessed. LEfSe analysis showed that, in Low PISA, species belonging to Lactobacillus, Roseburia, and Ruminococcus taxa and Lactobacillus zeae were enriched, while species belonging to Coprococcus, Clostridiales, and Atopobium were enriched in High PISA. Regression analyses showed that PISA associated with indicators of dysbiosis in the gut mainly reduced abundance of SCFA producing bacteria (Radj = -0.38, p = 0.03). Subgingival bacterial dysbiosis also associated with reduced levels of gut SCFA producing bacteria (Radj = -0.58, p = 0.002). These results suggest that periodontal inflammation and subgingival microbiota contribute to gut bacterial changes.

Periodontal Inflamed Surface Area (PISA) associates with composites of salivary cytokines.

BACKGROUND: Periodontal disease (PerioD) is a chronic, complex inflammatory condition resulting from the interaction between subgingival dysbiotic bacteria and the host immune response leading to local inflammation. Since periodontal inflammation is characterized by multiple cytokines effects we investigated whether Periodontal Inflamed Surface Area (PISA), a continuous measure of clinical periodontal inflammation is a predictor of composite indexes of salivary cytokines. METHODS AND FINDINGS: In a cross-sectional study of 67 healthy, well-educated individuals, we evaluated PISA and several cytokines expressed in whole stimulated saliva. Two salivary cytokine indexes were constructed using weighted and unweighted approaches based on a Principal Component Analysis [named Cytokine Component Index (CCI)] or averaging the (standardized) level of all cytokines [named Composite Inflammatory Index (CII)]. In regression analysis we found that PISA scores were significantly associated with both salivary cytokine constructs, (CCI: part R = 0.51, p<0.001; CII: part R = 0.40, p = 0.001) independent of age, gender and BMI showing that single scores summarizing salivary cytokines correlated with severity of clinical periodontal inflammation. CONCLUSIONS: Clinical periodontal inflammation may be reflected by a single score encompassing several salivary cytokines. These results are consistent with the complexity of interactions characterizing periodontal disease. In addition, Type I error is likely to be avoided.

Targeting the succinate receptor effectively inhibits periodontitis.

Periodontal disease (PD) is one of the most common inflammatory diseases in humans and is initiated by an oral microbial dysbiosis that stimulates inflammation and bone loss. Here, we report an abnormal elevation of succinate in the subgingival plaque of subjects with severe PD. Succinate activates succinate receptor-1 (SUCNR1) and stimulates inflammation. We detected SUCNR1 expression in the human and mouse periodontium and hypothesize that succinate activates SUCNR1 to accelerate periodontitis through the inflammatory response. Administration of exogenous succinate enhanced periodontal disease, whereas SUCNR1 knockout mice were protected from inflammation, oral dysbiosis, and subsequent periodontal bone loss in two different models of periodontitis. Therapeutic studies demonstrated that a SUCNR1 antagonist inhibited inflammatory events and osteoclastogenesis in vitro and reduced periodontal bone loss in vivo. Our study reveals succinate's effect on periodontitis pathogenesis and provides a topical treatment for this disease.

Study protocol for a randomised controlled trial of a care partner assisted intervention to improve oral health of individuals with mild dementia.

INTRODUCTION: Individuals with mild dementia are at high risk of poor oral health outcomes. To address this issue, we describe an intervention to teach care partners skills to guide individuals with mild dementia in proper oral hygiene techniques and provide reminders to practice oral hygiene care. By providing support to perform these tasks successfully, we aim to delay oral health decline among this vulnerable population. METHODS AND ANALYSIS: This multisite study is a three-arm randomised controlled trial. The primary objective is to evaluate the efficacy of an intervention to improve oral hygiene outcomes by promoting positive oral hygiene behaviours and skills among individuals with mild dementia. Care partners' behaviour factors, such as oral care self-efficacy and implementation of the care plan, serve as mediators of the intervention. Participant-care partner dyads will be randomly assigned to either Treatment Group 1, Treatment Group 2 or the Control Group. All groups will receive an educational booklet. Treatment Group 1 and Treatment Group 2 will receive a smart electronic toothbrush. Treatment Group 2 (the intervention group) will also receive an oral hygiene care skill assessment, personalised oral hygiene instruction and treatment plan; and care partners will receive in-home and telephone coaching on behaviour change. Oral health outcomes will be compared across the three groups. The duration of the active intervention is 3 months, with an additional 3-month maintenance phase. Data collection will involve three home visits: baseline, 3 months and 6 months. The study enrollment started in November 2021, and the data collection will end in Spring 2024. ETHICS AND DISSEMINATION: The study has been approved by the Institutional Review Board of the NYU Grossman School of Medicine and Duke University, and is registered at Clinicaltrials.gov. A Data Safety Monitoring Board has been constituted. The study findings will be disseminated via peer-reviewed publications, conference presentations and social media. TRIAL REGISTRATION NUMBER: NCT04390750.

Electronic Cigarette Use Promotes a Unique Periodontal Microbiome.

Electronic cigarettes (e-cigs) have become prevalent as an alternative to conventional cigarette smoking, particularly in youth. E-cig aerosols contain unique chemicals which alter the oral microbiome and promote dysbiosis in ways we are just beginning to investigate. We conducted a 6-month longitudinal study involving 84 subjects who were either e-cig users, conventional smokers, or nonsmokers. Periodontal condition, cytokine levels, and subgingival microbial community composition were assessed, with periodontal, clinical, and cytokine measures reflecting cohort habit and positively correlating with pathogenic taxa (e.g., Treponema, Saccharibacteria, and Porphyromonas). α-Diversity increased similarly across cohorts longitudinally, yet each cohort maintained a unique microbiome. The e-cig microbiome shared many characteristics with the microbiome of conventional smokers and some with nonsmokers, yet it maintained a unique subgingival microbial community enriched in Fusobacterium and Bacteroidales (G-2). Our data suggest that e-cig use promotes a unique periodontal microbiome, existing as a stable heterogeneous state between those of conventional smokers and nonsmokers and presenting unique oral health challenges. IMPORTANCE Electronic cigarette (e-cig) use is gaining in popularity and is often perceived as a healthier alternative to conventional smoking. Yet there is little evidence of the effects of long-term use of e-cigs on oral health. Conventional cigarette smoking is a prominent risk factor for the development of periodontitis, an oral disease affecting nearly half of adults over 30 years of age in the United States. Periodontitis is initiated through a disturbance in the microbial biofilm communities inhabiting the unique space between teeth and gingival tissues. This disturbance instigates host inflammatory and immune responses and, if left untreated, leads to tooth and bone loss and systemic diseases. We found that the e-cig user's periodontal microbiome is unique, eliciting unique host responses. Yet some similarities to the microbiomes of both conventional smokers and nonsmokers exist, with strikingly more in common with that of cigarette smokers, suggesting that there is a unique periodontal risk associated with e-cig use.

Electronic cigarette use enriches periodontal pathogens.

The effect of electronic cigarette (e-cigarette) smoking, especially its long-term impact on oral health, is poorly understood. Here, we conducted a longitudinal clinical study with two study visits, 6 months apart, to investigate the effect of e-cigarette use on the bacterial community structure in the saliva of 101 periodontitis patients. Our data demonstrated that e-cigarette use altered the oral microbiome in periodontitis patients, enriching members of the Filifactor, Treponema, and Fusobacterium taxa. For patients at the same periodontal disease stage, cigarette smokers and e-cigarette smokers shared more similarities in their oral bacterial composition. E-cigarette smoking may have a similar potential as cigarette smoking at altering the bacterial composition of saliva over time, leading to an increase in the relative abundance of periodontal disease-associated pathogens such as Porphyromonas gingivalis and Fusobacterium nucleatum. The correlation analysis showed that certain genera, such as Dialister, Selenomonas, and Leptotrichia in the e-cigarette smoking group, were positively correlated with the levels of proinflammatory cytokines, including IFN-γ, IL-1ß, and TNF-α. E-cigarette use was also associated with elevated levels of proinflammatory cytokines such as IFN-γ and TNF-α, which contribute to oral microbiome dysbiosis and advanced disease state.

Oral Health, Diabetes, and Inflammation: Effects of Oral Hygiene Behaviour.

INTRODUCTION: The aim of this research was to assess the association between inflammation and oral health and diabetes, as well as the mediating role of oral hygiene practice in this association. METHODS: Data were from the 2009-2010 National Health and Nutrition Examination Survey. The analytical sample consisted of 2,191 respondents aged 50 and older. Poor oral health was clinically defined by significant tooth loss (STL) and periodontal disease (PD). Diabetes mellitus (DM) was determined by glycemic levels. The outcome variable was serum C-reactive protein (CRP) level, dichotomised as ≥1 mg/dL (elevated CRP) vs <1 mg/dL (not elevated CRP). Two path models, one using STL and DM as the independent variable, the other using PD and DM as the independent variable, were estimated to assess the direct effects of having poor oral health and DM on elevated CRP and the mediating effects of dental flossing. RESULTS: In path model 1, individuals having both STL and DM (adjusted odds ratio [AOR], 1.92; 95% confidence interval [CI], 1.30-2.82) or having STL alone (AOR, 2.30; 95% CI, 1.68-3.15) were more likely to have elevated CRP than those with neither STL nor DM; dental flossing (AOR, 0.92, 95% CI, 0.88-0.96) was associated with lower risk of elevated CRP. In path model 2, no significant association was found between having both PD and DM and elevated CRP; dental flossing (AOR, 0.91; 95% CI:, 0.86-0.94) was associated with lower risk of elevated CRP. CONCLUSIONS: Findings from this study highlight the importance of improving oral health and oral hygiene practice to mitigate inflammation. Further research is needed to assess the longer-term effects of reducing inflammation.

Effects of the Co-occurrence of Diabetes Mellitus and Tooth Loss on Cognitive Function.

OBJECTIVE: Both diabetes mellitus (DM) and poor oral health are common chronic conditions and risk factors of Alzheimer's disease and related dementia among older adults. This study assessed the effects of DM and complete tooth loss (TL) on cognitive function, accounting for their interactions. METHODS: Longitudinal data were obtained from the 2006, 2012, and 2018 waves of the Health and Retirement Study. This cohort study included 7,805 respondents aged 65 years or older with 18,331 person-year observations. DM and complete TL were self-reported. Cognitive function was measured by the Telephone Interview for Cognitive Status. Random-effect regressions were used to test the associations, overall and stratified by sex. RESULTS: Compared with older adults without neither DM nor complete TL, those with both conditions (b = -1.35, 95% confidence interval [CI]: -1.68, -1.02), with complete TL alone (b = -0.67, 95% CI: -0.88, -0.45), or with DM alone (b = -0.40, 95% CI: -0.59, -0.22), had lower cognitive scores. The impact of having both conditions was significantly greater than that of having DM alone (p < .001) or complete TL alone (p = 0.001). Sex-stratified analyses showed the effects were similar in males and females, except having DM alone was not significant in males. CONCLUSION: The co-occurrence of DM and complete TL poses an additive risk for cognition. Healthcare and family-care providers should pay attention to the cognitive health of patients with both DM and complete TL. Continued efforts are needed to improve older adults' access to dental care, especially for individuals with DM.

Current Considerations for Clinical Management and Care of People with HIV: Findings from the 11th Annual International HIV and Aging Workshop.

The number of people with HIV (PWH) aged 50 years or older continues to steadily increase. The convergence of age- and HIV-related complications in these individuals presents a challenge for both patients and clinicians alike. New findings continue to emerge, as numerous researchers evaluate the combined impact of these two factors on quality of life, physiological systems, and mental health in PWH. Since its first occurrence in 2009, the International Workshop on HIV and Aging has served as a multidisciplinary meeting to share basic biomedical data, clinical trial results, treatment strategies, and epidemiological recommendations, toward better understanding and outcomes among like-minded scientific professionals. In this article, we share a selection of key findings presented in plenary talks at the 11th Annual International Workshop on HIV and Aging, held virtually from September 30, 2020 to October 2, 2020. We will also address the future directions of HIV and aging research, to further assess how the aging process intersects with chronic HIV.

Opportunities, barriers, and recommendations in down syndrome research.

BACKGROUND: Recent advances in medical care have increased life expectancy and improved the quality of life for people with Down syndrome (DS). These advances are the result of both pre-clinical and clinical research but much about DS is still poorly understood. In 2020, the NIH announced their plan to update their DS research plan and requested input from the scientific and advocacy community. OBJECTIVE: The National Down Syndrome Society (NDSS) and the LuMind IDSC Foundation worked together with scientific and medical experts to develop recommendations for the NIH research plan. METHODS: NDSS and LuMind IDSC assembled over 50 experts across multiple disciplines and organized them in eleven working groups focused on specific issues for people with DS. RESULTS: This review article summarizes the research gaps and recommendations that have the potential to improve the health and quality of life for people with DS within the next decade. CONCLUSIONS: This review highlights many of the scientific gaps that exist in DS research. Based on these gaps, a multidisciplinary group of DS experts has made recommendations to advance DS research. This paper may also aid policymakers and the DS community to build a comprehensive national DS research strategy.

Periodontal dysbiosis associates with reduced CSF Aß42 in cognitively normal elderly.

INTRODUCTION: Periodontal disease is a chronic, inflammatory bacterial dysbiosis that is associated with both Alzheimer's disease (AD) and Down syndrome. METHODS: A total of 48 elderly cognitively normal subjects were evaluated for differences in subgingival periodontal bacteria (assayed by 16S rRNA sequencing) between cerebrospinal fluid (CSF) biomarker groups of amyloid and neurofibrillary pathology. A dysbiotic index (DI) was defined at the genus level as the abundance ratio of known periodontal bacteria to healthy bacteria. Analysis of variance/analysis of covariance (ANOVA/ANCOVA), linear discriminant effect-size analyses (LEfSe) were used to determine the bacterial genera and species differences between the CSF biomarker groups. RESULTS: At genera and species levels, higher subgingival periodontal dysbiosis was associated with reduced CSF amyloid beta (Aß)42 (P = 0.02 and 0.01) but not with P-tau. DISCUSSION: We show a selective relationship between periodontal disease bacterial dysbiosis and CSF biomarkers of amyloidosis, but not for tau. Further modeling is needed to establish the direct link between oral bacteria and Aß.

Cognitive dysfunction in young subjects with periodontal disease.

BACKGROUND: Periodontal disease is an inflammatory, dysbiotic condition. Studies have shown that in the elderly, periodontal disease was associated with cognitive dysfunction and Alzheimer's disease. OBJECTIVE: To investigate whether young healthy subjects with periodontal disease have lower cognition compared to those without periodontal disease. The salivary cytokines (IL-1ß, TNF-α) levels in relation to cognition were also tested. METHODS: In a monocenter, cross-sectional study, forty subjects [mean age (SD) = 34 (5) and 48% female] from western Romania were classified into periodontal disease conditions using radiographic assessment: 10 subjects had aggressive periodontitis (AGG_P), 20 chronic mild-moderate periodontitis (CR_P), and 10 no periodontitis (NL_P). Neuropsychological assessment performed by standardized neurologists and psychologist included Rey Auditory Verbal Learning Test (RAVLT), Montreal Cognitive Assessment test (MOCA), Mini-Mental State Examination (MMSE), and Prague tests. Salivary cytokines levels were determined by ELISA. RESULTS: RAVLT and MOCA delayed recall scores were lower in AGG_P group compared to NL_P and CR_P. The learning curve was also different with subjects with AGG_P showing reduced learning performance. Contrary to our hypothesis, salivary IL-1ß associated with immediate but not delayed cognitive scores. CONCLUSIONS: These results showed for the first time that subjects with AGG_P had cognitive dysfunction and IL-1ß may play a role in this process.

Comparative Effects of E-Cigarette Aerosol on Periodontium of Periodontitis Patients.

Introduction: Tobacco use is one of the main causes of periodontitis. E-cigarette are gaining in popularity, and studies are needed to better understand the impact of e-cigarettes on oral health. Objective: To perform a longitudinal study to evaluate the adverse effects of e-cigarettes on periodontal health. Methods: Naïve E-cigarette users, cigarette smokers, and non-smokers were recruited using newspaper and social media. Age, gender, and ethnicity, were recorded. Participants were scheduled for two visits 6 months apart. At each visit, we collected data on the frequency and magnitude of e-cigarette and cigarette use, and alcohol consumption. Carbon monoxide (CO) levels, cotinine levels, salivary flow rate, periodontal probing depth (PD), bleeding on probing (BoP), and clinical attachment loss (CAL) were also determined at both baseline and follow-up visits and compared between groups with two-way repeated measures ANOVA. Periodontal diagnosis and other categorical variables were compared between groups with the chi-square statistic and logistic regression. Results: We screened 159 subjects and recruited 119 subjects. One-hundred-one subjects (31 cigarette smokers, 32 e-cigarette smokers, and 38 non-smokers) completed every assessment in both visits. The retention and compliance rate of subjects was 84.9%. The use of social media and craigslist was significant in recruiting e-cigarette subjects. Ethnicity and race differed between groups, as did average age in the male subjects. Carbon monoxide and salivary cotinine levels were highest among cigarette smokers. Bleeding on probing and average PDs similarly increased over time in all three groups, but CAL uniquely increased in e-cigarette smokers. Rates of severe periodontal disease were higher in cigarette smokers and e-cigarette users than non-smokers, but interpretation is confounded by the older age of the cigarette smokers. Conclusion: Among the recruited participants, CAL after 6 months was significantly worse only in the e-cigarette smokers. This study design and protocol will assist in future larger studies on e-cigarette and oral health.

The Brain-Nose Interface: A Potential Cerebrospinal Fluid Clearance Site in Humans.

The human brain functions at the center of a network of systems aimed at providing a structural and immunological layer of protection. The cerebrospinal fluid (CSF) maintains a physiological homeostasis that is of paramount importance to proper neurological activity. CSF is largely produced in the choroid plexus where it is continuous with the brain extracellular fluid and circulates through the ventricles. CSF movement through the central nervous system has been extensively explored. Across numerous animal species, the involvement of various drainage pathways in CSF, including arachnoid granulations, cranial nerves, perivascular pathways, and meningeal lymphatics, has been studied. Among these, there is a proposed CSF clearance route spanning the olfactory nerve and exiting the brain at the cribriform plate and entering lymphatics. While this pathway has been demonstrated in multiple animal species, evidence of a similar CSF egress mechanism involving the nasal cavity in humans remains poorly consolidated. This review will synthesize contemporary evidence surrounding CSF clearance at the nose-brain interface, examining across species this anatomical pathway, and its possible significance to human neurodegenerative disease. Our discussion of a bidirectional nasal pathway includes examination of the immune surveillance in the olfactory region protecting the brain. Overall, we expect that an expanded discussion of the brain-nose pathway and interactions with the environment will contribute to an improved understanding of neurodegenerative and infectious diseases, and potentially to novel prevention and treatment considerations.

The Influences of Bioinformatics Tools and Reference Databases in Analyzing the Human Oral Microbial Community.

There is currently no criterion to select appropriate bioinformatics tools and reference databases for analysis of 16S rRNA amplicon data in the human oral microbiome. Our study aims to determine the influence of multiple tools and reference databases on α-diversity measurements and ß-diversity comparisons analyzing the human oral microbiome. We compared the results of taxonomical classification by Greengenes, the Human Oral Microbiome Database (HOMD), National Center for Biotechnology Information (NCBI) 16S, SILVA, and the Ribosomal Database Project (RDP) using Quantitative Insights Into Microbial Ecology (QIIME) and the Divisive Amplicon Denoising Algorithm (DADA2). There were 15 phyla present in all of the analyses, four phyla exclusive to certain databases, and different numbers of genera were identified in each database. Common genera found in the oral microbiome, such as Veillonella, Rothia, and Prevotella, are annotated by all databases; however, less common genera, such as Bulleidia and Paludibacter, are only annotated by large databases, such as Greengenes. Our results indicate that using different reference databases in 16S rRNA amplicon data analysis could lead to different taxonomic compositions, especially at genus level. There are a variety of databases available, but there are no defined criteria for data curation and validation of annotations, which can affect the accuracy and reproducibility of results, making it difficult to compare data across studies.

Periodontal disease as a possible cause for Alzheimer's disease.

Approximately 47 million people worldwide have been diagnosed with dementia, 60%-80% of whom have dementia of the Alzheimer's disease type. Unfortunately, there is no cure in sight. Defining modifiable risk factors for Alzheimer's disease may have a significant impact on its prevalence. An increasing body of evidence suggests that chronic inflammation and microbial dysbiosis are risk factors for Alzheimer's disease. Periodontal disease is a chronic inflammatory disease that develops in response to response to microbial dysbiosis. Many studies have shown an association between periodontal disease and Alzheimer's disease. The intent of this paper was to review the existing literature and determine, using the Bradford Hill criteria, whether periodontal disease is causally related to Alzheimer's disease.

Electronic Cigarette Aerosol Modulates the Oral Microbiome and Increases Risk of Infection.

The trend of e-cigarette use among teens is ever increasing. Here we show the dysbiotic oral microbial ecology in e-cigarette users influencing the local host immune environment compared with non-smoker controls and cigarette smokers. Using 16S rRNA high-throughput sequencing, we evaluated 119 human participants, 40 in each of the three cohorts, and found significantly altered beta-diversity in e-cigarette users (p = 0.006) when compared with never smokers or tobacco cigarette smokers. The abundance of Porphyromonas and Veillonella (p = 0.008) was higher among vapers. Interleukin (IL)-6 and IL-1ß were highly elevated in e-cigarette users when compared with non-users. Epithelial cell-exposed e-cigarette aerosols were more susceptible for infection. In vitro infection model of premalignant Leuk-1 and malignant cell lines exposed to e-cigarette aerosol and challenged by Porphyromonas gingivalis and Fusobacterium nucleatum resulted in elevated inflammatory response. Our findings for the first time demonstrate that e-cigarette users are more prone to infection.

Periodontal disease in a young Romanian convenience sample: radiographic assessment.

BACKGROUND: The goal of this study was to determine the distribution of periodontal disease in a population seeking oral rehabilitation in a Romanian prosthodontics department and to identify the factors associated with each type of periodontal condition. METHODS: The study population consisted of patients presenting consecutively to the Prosthodontics Department of the Faculty of Dental Medicine, Victor Babes University of Medicine and Pharmacy, Timisoara. The diagnosis and classification of periodontal conditions, as well as dental pathologies and conditions, were based on examination of panoramic radiographs. A standardized questionnaire was administered to obtain socio-demographic characteristics (age, gender, ethnicity, education, residency, marital status), medical history, dental/periodontal history (family history of periodontal disease), and behavior (smoking, brushing, flossing and regular cleaning). RESULTS: Among subjects presenting to the Prosthodontics department, only 34.2% were periodontal disease-free and 65.8% had periodontal disease, of which 11.4% had aggressive periodontitis. In univariate models, age, education, marital status, smoking, and tooth number were associated with chronic periodontitis. Age, education, family history, smoking, and tooth number were associated with aggressive periodontitis. However, in a multivariable model, only age, tooth number and family history were significant. CONCLUSIONS: This study found a high prevalence of periodontal disease in patients seeking oral rehabilitation from the Prosthodontics department. Age, tooth number and family history of periodontal disease were associated with the type of periodontal disease. These results suggest the need for periodontal examination prior to prosthetic oral rehabilitation in this population.

Periodontal disease's contribution to Alzheimer's disease progression in Down syndrome.

People with Down syndrome (DS) are at an increased risk for Alzheimer's disease (AD). After 60 years of age, >50% of DS subjects acquire dementia. Nevertheless, the age of onset is highly variable possibly because of both genetic and environmental factors. Genetics cannot be modified, but environmental risk factors present a potentially relevant intervention for DS persons at risk for AD. Among them, inflammation, important in AD of DS type, is potential target. Consistent with this hypothesis, chronic peripheral inflammation and infections may contribute to AD pathogenesis in DS. People with DS have an aggressive form of periodontitis characterized by rapid progression, significant bacterial and inflammatory burden, and an onset as early as 6 years of age. This review offers a hypothetical mechanistic link between periodontitis and AD in the DS population. Because periodontitis is a treatable condition, it may be a readily modifiable risk factor for AD.

Effects of vascular risk factors, statins, and antihypertensive drugs on PiB deposition in cognitively normal subjects.

INTRODUCTION: Hypertension, hypercholesterolemia, and obesity increase the risk of dementia. Although their detection is commonly followed by an introduction of treatment, little is known about how medications frequently used to treat vascular risk affect amyloid deposition. METHODS: A cross-sectional study of 156 subjects who underwent positron emission tomography with PiB. Using linear regression, we tested whether blood pressure, cholesterol, overweight/obese status, angiotensin receptor blockers (ARBs), beta-blockers, diuretics, angiotensin converting enzyme inhibitors, and statins predicted amyloid deposition. RESULTS: The use of ARBs (ß = -.15, P = .044) and diuretics (ß = -.20, P = .006) predicted less amyloid accumulation; older age (ß = .29, P < .001) and statins (ß = .23, P = .004) were related to greater amyloid deposition. Overweight and/or obese women had more cortical amyloid than their peers. DISCUSSION: Prospective studies should confirm effects of drugs and increased body weight on amyloid accumulation and establish whether they translate into measurable clinical outcomes. Women may be more susceptible to harmful effects of obesity.