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Background: Variability in cognitive decline among adults with Alzheimer's disease (AD) is seen across studies. While such variability is often modelled using linear models, in the Australian Imaging, Biomarkers and Lifestyle (AIBL) study, application of a sigmoidal methodology has shown excellent precision in modelling cognitive and biomarker changes. Here we expand these findings by examining associations of brain volumes in AD specific Regions of Interest (ROIs) with accelerated cognitive decline among amyloid‐beta positive (Ab+) AIBL participants. Method: Longitudinal cognitive scores for the AIBL PACC, Language, Visuospatial functioning and CDR‐SB were mapped to sigmoidal trajectories, with a threshold defining the inflection point of accelerated cognitive decline. Participants to the left of the threshold were classified as having non‐accelerated decline (non‐accelerators), and participants beyond the threshold were classed as accelerators (Figure 1B). Using these classifications, we investigated differences in 16 ICV corrected ROI (left and right hemispheres pooled) for reductions in brain volume via generalised linear models adjusted for age, gender, and APOE‐e4 status. Three participant subgroups were tested: 1) Ab+/Tau unknown, 2) Ab+/Tau‐ and 3) Ab+/Tau+. Significant t‐values for the summed ROI volumes were mapped on a standard brain mesh for visualisation. Result: Of regions tested, two stood out consistently amongst top markers in each of the participant subgroups and cognitive outcomes: 1) supramarginal volume and 2) middle temporal volume (Figure 1C). Largest volume differences between accelerators and non‐accelerators were seen in the Ab+/Tau+ group; whilst smallest p‐values were in the Ab+/Tau unknown group due to a larger sample size (Table 1). Brain mesh visualization showed most of the AD signature ROIs altered in accelerator groups as compared with non‐accelerator groups. Figure 1D shows the AD signature for each cognitive outcome amongst the Ab+/Tau participant group. Top ranked ROI for the left being middle temporal volume (T=7.10, PACC) and supramarginal volume (T=7.10, CDR‐SB). Conclusion: Sigmoid analyses of MRI using binary cognitive scores show decreased ROI volumes in AIBL Ab+ participants with accelerated cognitive decline. This effect was mediated by known information on Tauopathy. Whilst effect sizes were high, smaller sample sizes in some groups affected p‐values and should therefore be replicated in larger samples. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) significantly impacts individuals, families, and society worldwide. In Europe, it affects approximately 10 million people, leading to considerable healthcare costs, caregiver burden, and reduced productivity.1 It is crucial to slow down AD progression in order to alleviate the rising burden of the disease. Method: Two targeted reviews were conducted, one on the prevalence of individuals with biomarker‐confirmed AD pathology and the other on the costs associated with AD by disease stage and care setting. The most recent prevalence1,2,3,4,5,6,7,8 and cost9,10,11,12,13,14,15,16,17,18 data were identified for selected countries, including the UK, France, Germany, Italy, Spain, Sweden, Netherlands, Finland, Switzerland, Estonia, and the Czech Republic. Regression‐based or linear extrapolation methods were applied to fill the existing data gaps where appropriate. All costs were converted to USD and adjusted for inflation to reflect 2022 values. Result: The national costs associated with annual transitions across all AD stages were estimated to be ($11.4bn) in Germany, followed by France ($6.2bn), UK ($5.2bn), Spain ($3.7bn), Italy ($3.2bn), Switzerland ($1.9bn), Sweden ($1.4bn), Netherlands ($1.07bn), Finland ($0.8bn), Czech Republic ($0.7bn), and Estonia ($0.03bn). Early‐stage progression, with the largest number of individuals transitioning from mild cognitive impairment (MCI) to mild AD, accounted for more than half of the total transitioning costs in the UK, Spain, Finland, Netherlands, Czech Republic, and Estonia. However, the highest cost burden varied across the countries. In Germany, Italy, and Switzerland, similar to previous estimates for the US,19 the highest burden was associated with late‐stage progression from moderate to severe dementia, despite the relatively lower number of such transitions. This is likely due to the more expensive institutional care in these countries. Our findings further suggest that including the economic value of uncompensated caregiving substantially increases the total costs while leading to greater variability in estimates. The interpretation of these results should take into account data limitations and the assumptions made in the analysis. Conclusion: The economic burden of AD increases as disease progresses. Total costs and the underlying components vary across health systems and regions. Nevertheless, universally, any treatment that slows down the disease progression could result in substantial costs savings. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) is a multifactorial disease characterised by a long period of neuronal loss which manifests clinically as cognitive decline and ultimately dementia. Understanding the nature and magnitude of cognitive decline prior to dementia is critical to understanding the disease course. Here we quantify change in six cognitive composite scores to compare their temporal sequence and rates of change early in the AD disease course. Method: Amyloid‐beta positive (Aβ+) cognitively unimpaired (CU), MCI and AD participants from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of ageing with ≥three study visits (N = 857), were used to derive composite scores for executive function, language, attention and processing, recognition, visuospatial, and a general composite used in clinical trials (AIBL‐PACC). A multivariate method for combining cognitive change trajectory curves was used to place each composite score trajectory in a common numerical space. Using the mean AIBL‐PACC scores for the prodromal group (MCI‐Aβ+) as a reference, change over a three‐year period for each composite was estimated. Given the AIBL requirement for a minimum 1.5 SD change in two or more cognitive domains to justify progression to MCI/AD, disease time was set with the zero point at a ‐1.5 AIBL‐PACC score, representing a 1.5 SD decline in AIBL‐PACC from the mean CU Ab‐ population at baseline. Result: The AIBL‐PACC, language and visuospatial functioning scores showed the steepest trajectories indicating AD related decline in these scores was fastest (Figure 1). AIBL‐PACC reached the ‐1.5 point on the y‐axis first followed closely by memory recognition, with steeper trajectory of decline for the AIBL‐PACC across the age range. Focusing on AIBL‐PACC, it took 2.15 years to transition from ‐1.5 to the mean of the prodromal group (‐1.87). At five years past the start of the prodromal stage, the data suggests a drop in the AIBL‐PACC to ‐2.54, an approximate decline of ∼0.22 points per year. Conclusion: This is the first presentation of a novel multivariate disease trajectory method examining expected change across the AD continuum among Aβ+ persons. A 3‐year change in the PACC composite demonstrated here will be relevant to measure disease progression during clinical trials. [ABSTRACT FROM AUTHOR]

Background: Cerebral microbleeds (CMBs) are common in the elderly population and are associated with cognitive decline. The aim of the current study was to examine the association between CMBs and cerebral amyloid pathology in cognitively unimpaired (CU) and cognitively impaired (CI) individuals included in the Amyloid Biomarker Study. Method: We included 2550 CU and 1002 CI participants from 12 cohorts of the Amyloid Biomarker Study. Presence of amyloid pathology was determined based on Aß42 levels in CSF (n = 2873) or amyloid‐PET (n = 679) using data‐driven or center‐specific cutoffs. CMBs were assessed on in vivo MRI and were classified as present (≥1) or absent. The association of amyloid pathology with CMBs and its dependency on age, sex, APOE‐e4 carriership and hypertension was assessed using generalized‐estimating‐equations. Result: Thirty‐seven percent of participants were amyloid positive, 38% were APOE‐e4 carrier, 54% were female, 30% had hypertension and 17% had CMBs (20% of the amyloid positive and 16% of the amyloid negative group, respectively). The mean age was 66.7 years (SD9.2). In CU participants, there was no association between amyloid pathology and CMBs. In CI individuals, CMB prevalence was associated with amyloid pathology depending on age (p = 0.044). At younger ages (<75 years), CMBs were more common in amyloid positive rather than amyloid negative participants while at older ages, amyloid negative participants had CMBs more often. However, the interaction between amyloid status and age became insignificant when hypertension was considered. CMB prevalence was associated with amyloid pathology depending on hypertension (p = 0.006). In CI participants without hypertension, CMBs were more common in those that were amyloid positive rather than amyloid negative. In CI participants with hypertension, there was no significant difference in CMB prevalence between the amyloid positive and negative groups (Figure 1). Sex and APOE‐e4 status did not affect the observed associations between amyloid pathology and CMBs in participants with CI. Conclusion: CMB prevalence is associated with amyloid pathology and this association is dependent on hypertension. Knowledge on the background prevalence of CMBs considering AD biomarker and vascular risk factor status is needed to inform clinical trial design and safety evaluation of AD therapies. [ABSTRACT FROM AUTHOR]

Background: Prevalence estimates of amyloid positivity in persons across the AD clinical spectrum are important to reduce screen failure rates and improve recruitment efficiency in anti‐amyloid trials. We have previously estimated the prevalence according to age, sex, education and APOE genotype. It is however unknown whether these prevalence estimates generalize to diverse ethnoracial groups. We here aim to estimate the prevalence of amyloid abnormality in Black, White and Asian persons without dementia and examine associations with age, sex, educational level and APOE‐e4 carrier status. Method: We selected 7,419 participants (6,083 with normal cognition; 1,336 with MCI) from 9 Amyloid Biomarker Study cohorts, including 291 Black, 6,310 White and 818 Asian participants. Amyloid positivity was determined with a PET (n = 5,714) or CSF (n = 1,705) biomarker, using data‐driven or study‐specific cutoffs. Generalized estimating equations were used to estimate the age‐related prevalence by ethnoracial group and to evaluate moderation by APOE‐e4 carrier status while adjusting for sex and education. Result: The mean age was 70.9+‐7.4 years, 3,848 (57%) were women, and 20% were APOE‐e4 carriers. In persons with normal cognition, the age‐related prevalence of amyloid positivity was higher for White (25%) than for Black (17%) and Asian (16%) participants (p = 0.016). Among APOE‐e4 carriers with normal cognition, the prevalence of amyloid abnormality was again higher for White (46%) than for Black (29%) and Asian (30%) participants (Asian vs Black p‐value = 0.046, Asian vs White p‐value<0.001, Black vs White p‐value<0.001). Among APOE‐e4 noncarriers, no differences among the ethnoracial groups were identified (p = 0.56). In persons with MCI, White (59%) and Asian (60%) participants had abnormal amyloid more often than Black participants (43%; p<0.001). Ethnoracial differences were similar for APOE‐e4 carriers and noncarriers with MCI. Conclusion: In persons with normal cognition, the prevalence of amyloid abnormality among APOE‐e4 carriers was ∼15% higher for White than for Black and Asian participants, while among APOE‐e4 noncarriers no ethnoracial differences were found. In persons with MCI, both White and Asian participants ∼15% more often had abnormal amyloid than Black participants, irrespective of APOE‐e4 carrier status. Ethnoracial status may be an important factor to consider in the design of AD clinical trials. [ABSTRACT FROM AUTHOR]

Background: We have updated our previous amyloid positivity prevalence estimates (Jansen, 2015; Ossenkoppele, 2015; Table 1) with data from 19,097 individuals from 85 cohorts. We tested if prevalence estimates differed for positron emission tomography (PET) or cerebrospinal fluid (CSF) amyloid. We calculated data‐driven CSF cut‐points as previous studies suggested a drift in Innotest‐assay performance. Method: We included 9,908 participants with normal cognition (CN); 1,542 with subjective cognitive decline (SCD); 5,405 with mild cognitive impairment (MCI); and 2,260 with clinical Alzheimer's disease (AD) dementia. 10,139 participants had an amyloid‐PET measure and 8,958 participants had an amyloid‐CSF measure. Amyloid‐ß aggregation was originally dichotomized as normal or abnormal according to study‐specific cut‐points, and we defined data‐driven CSF cut‐points using Gaussian mixture modelling. Generalized‐estimating‐equations adjusting for within‐study clustering of individuals were used to estimate amyloid positivity prevalence according to age, cognitive status, and biomarker modality and compared original with updated cut‐points. Result: Amyloid positivity prevalence was higher with older age and advancing disease severity. Using original cut‐points as provided by the cohort, the prevalence of amyloid positivity at the median age of 70 was similar for PET and CSF estimates for CN (24%), SCD (26%), and MCI (51%), and was higher in PET (87%) than CSF (79%) for clinical AD dementia. Using the data‐driven CSF cut‐points, the prevalence of amyloid positivity was higher for CSF‐based estimates than PET‐based estimates in CN (CSF 33%, PET 24%), SCD (CSF 36%, PET 27%), and MCI (CSF 60%, PET 49%), but comparable in CSF and PET in clinically diagnosed AD dementia (CSF 83%, PET 87) (Table 1, Figure 1). Conclusion: We provide updated amyloid positivity estimates from the Amyloid Biomarker Study. CSF‐based estimates using a data‐driven approach resulted in higher estimates (up to 11% higher) in people without clinical AD dementia than PET‐based estimates. Whether CSF‐based estimates are more sensitive than PET‐based estimates for amyloid pathology among people without dementia needs to be explored in cohorts that use both modalities. These updated estimates may be useful to understand potential eligible patient population sizes for anti‐amyloid therapies and to inform recruitment strategies for clinical trials investigating anti‐amyloid therapies. [ABSTRACT FROM AUTHOR]

Background: Studies suggest dementia patients have higher rates of non‐traumatic intracranial hemorrhage (nt‐ICH) compared to cognitively‐unimpaired peers. Recent studies also suggest increased risk of nt‐ICH, following infection with Covid‐19 in the general population. However, the risk of nt‐ICH following Covid‐19 infection in cognitively‐impaired individuals is currently unknown. Method: Using US electronic health records ICD codes, we matched Alzheimer's disease (AD), dementia, and mild cognitive impairment (MCI) cases with a history of Covid‐19 to similarly cognitively impaired controls without Covid‐19 history and examined incidence of nt‐ICH over six‐months following infection. Cases and controls were propensity score matched on age, sex, race, ethnicity, time since cognitive‐diagnosis, anticoagulant use, antiplatelet use, and 37 comorbidities. Analyses focused on the first year of the pandemic in 2020, prior to availability of at‐home tests and vaccines, to reduce misclassification bias. Individuals with prior history of nt‐ICH, traumatic ICH, or stroke were excluded to focus on incident nt‐ICH. Cox proportional hazard models compared risk between those with and without Covid‐19. Result: Our sample included 2,287 AD cases with Covid‐19 matched to 6,861 AD controls; 5,726 dementia cases matched to 17,178 dementia controls; and 807 MCI cases matched to 2,419 MCI controls. The incidence of nt‐ICH following Covid‐19, among AD cases, was 12.53/1,000 person‐years (95% CI: 7.66‐19.36) vs. 4.16/1,000 person‐years (95% CI: 2.51‐6.50) in AD patients without Covid‐19; HR = 3.1 (95% CI: 1.7, 5.8), p = 0.0004. Similarly in dementia patients, Covid‐19 increased the risk by 3.0 times (95% CI: 1.8, 4.7), p<0.0001. The incidence in dementia Covid‐19 cases was 8.48/1,000 person‐years (95% CI: 5.91, 11.80) vs. 2.97/1,000 person‐years (95% CI: 2.07, 4.13) in dementia patients without a history of Covid‐19 over the study period. The incidence in MCI patients with a history of Covid‐19 was 5.03/1,000 person‐years (95% CI: 1.37, 12.87), vs. 1.56/1,000 person‐years (95% CI: 0.32, 4.57) in MCI controls, but risk was not significantly different; HR = 3.4 (95% CI: 0.8, 15.0), p = 0.11. Conclusion: Although nt‐ICH was rare among cognitively impaired patients following Covid‐19 infection in 2020, the risk over 6‐months in AD and dementia cases was approximately 3 times higher than controls without a history of Covid‐19. [ABSTRACT FROM AUTHOR]

Background: The relationship between lifestyle factors and Alzheimer's disease pathophysiology is not well understood. The aim of this study was to assess the cross‐sectional association between lifestyle factors and amyloid abnormality in individuals with normal cognition (NC) and mild cognitive impairment (MCI). Method: We selected 39 cohorts from the Amyloid Biomarker Study. Self‐reported lifestyle data were available for 8924 participants with NC and 2403 participants with MCI. Amyloid abnormality was determined with amyloid‐PET (center‐specific cutoffs) or with aß42 level in CSF (data‐driven or center‐specific cutoffs). Lifestyle data was harmonized across cohorts and dichotomized into ever smoked yes/no, current alcohol consumption yes/no, currently physically active yes/no and current sleep problems yes/no. Education was dichotomized into 'high' or 'low' at the median of 16 years. Generalized estimating equations with amyloid abnormality as outcome and single lifestyle factors as predictors were used. Interactions with age, sex, education, cognitive status and APOE‐e4 carrier status were assessed and these variables were added as covariates to all models. Result: Thirty‐one percent of participants were amyloid positive, 37% were ApoE‐4 carrier, and 55% were female. The mean age was 68.7 (SD8.7). Twenty‐five percent of participants smoked, 54% consumed alcohol, 30% experienced sleep problems and 25% were physically inactive. Overall, smoking was associated with a slightly increased prevalence of amyloid abnormality (2%; p = 0.03). In NC, sleep problems were unrelated to the prevalence of amyloid abnormality while in MCI, sleep problems were associated with a lower prevalence (15.3%; p<0.001). Physical activity was related to higher prevalence of amyloid abnormality in APOE‐e4 carriers (5.9%; p<0.001) while this association was not found in noncarriers. Age, sex and educational level did not modify the identified associations between lifestyle factors and amyloid abnormality. Alcohol consumption was unrelated to amyloid abnormality. Conclusion: Smoking behavior, sleep quality, and physical activity were associated with amyloid abnormality depending on cognitive and APOE‐e4 status. A better understanding of the associations between lifestyle factors and cerebral amyloid pathology in different subgroups will aid in identifying those at risk and contribute to the development of targeted intervention strategies. [ABSTRACT FROM AUTHOR]

Background: While Black/African Americans and Latinx/Hispanics have nearly twice the risk of developing Alzheimer's disease compared to Non‐Hispanic Whites, their involvement in clinical research and trials remains low. Due to the lack of data and underrepresentation in research, it is unknown if there are clinicopathological differences in Alzheimer's disease or response to therapies. We have established specific recruitment goals for underrepresented groups in the aducanumab Phase 3b/4 confirmatory ENVISION study, which is a multicenter, randomized, double‐blind, placebo‐controlled, parallel‐group study of participants with mild cognitive impairment and mild dementia stages of Alzheimer's disease (Stages 3 and 4; NCT05310071), designed to better understand the efficacy and safety of aducanumab treatment for these populations. Method: Epidemiological and clinical data by race/ethnicity in the United States (US) were obtained from systematic literature reviews and Clinical trial data were then used to characterize the clinicopathological profile of Alzheimer's disease among diverse groups. Data from underrepresented participants were pooled and analyzed contemporaneous Alzheimer's disease clinical trials to identify potential differences (i.e., heterogeneity) in clinical and biomarker outcomes. Result: Based on epidemiological analyses, the ENVISION has an enrollment target of 18% for patient populations historically underrepresented in clinical trials in the US. Limited pooled clinical trial data suggests there may be greater heterogeneity in clinical and biomarker endpoints in underrepresented groups. Conclusion: Research and clinical trial data from diverse patient populations with Alzheimer's disease are lacking. Inclusive research is essential to advancing the mission to develop treatments for this devastating disease. Data‐driven recruitment goals have been established and analyses planned to address the safety and efficacy of aducanumab in historically underrepresented populations in the ENVISION study. This could serve as a model for evaluating differences in treatment outcomes across racial/ethnic groups. [ABSTRACT FROM AUTHOR]

Background: The association of amyloid abnormality with cognitive decline in persons with normal cognition (NC) and mild cognitive impairment (MCI) is important to guide AD trial design and understand prognoses. We examined the relation between amyloid abnormality and decline over time in several cognitive domains, and tested whether apolipoprotein (APOE)‐e genotype modified this association. Method: We included 3,820 persons (2,599 NC, 1,221 all‐cause MCI) from 22 Amyloid Biomarker Study cohorts, with baseline PET (n = 846) or CSF (n = 2,974) amyloid measurements available. Amyloid abnormality on PET was based on visual read or cohort‐specific cutoffs, and for CSF on cohort‐specific or data‐driven cutoffs. Global cognition was assessed by Mini‐Mental State Examination (MMSE), functional performance by Clinical Dementia Rating global scale (CDR), and memory immediate and delayed recall by verbal learning tests. We examined baseline amyloid abnormality associations with cognitive performance over time and potential modification by APOE‐e (up to 3‐way interactions) using random‐slope/random‐intercept linear mixed‐models corrected for age, sex, education with random cohort effects. Result: Mean follow‐up duration was 2.1 (range 0.5‐8) years. Baseline MMSE was worse in persons with abnormal‐amyloid compared with normal‐amyloid (NC mean difference = 0.2, p = 0.04, MCI mean difference = 2.4, p<0.001). In NC, amyloid abnormality was not associated with decline in any domain (Table 1), nor was the association influenced by APOE‐e4. In MCI, amyloid abnormality was associated with lower baseline performance and steeper decline on all domains (Table 1). In APOE‐e4‐carriers with MCI, MMSE decline was steeper than in non‐carriers (p<0.001, 1.5x steeper in amyloid‐abnormal, 3x steeper in amyloid‐normal). The rate of decline on immediate/delayed recall in MCI was higher in APOE‐e4‐carriers than non‐carriers, independent of amyloid status (p<0.001). For both NC and MCI, decline was steepest in persons with e4e4, followed by e3e4, e3e3, e2e4, and e2e3 (p = 0.001, Figure 1), independent of amyloid status. Conclusion: Amyloid abnormality was not associated with cognitive decline in persons with NC after a short‐term follow‐up. In MCI, amyloid abnormality was closely associated with cognitive decline in several domains, with an additive effect of APOE‐e on decline. These results may be relevant for future trial recruitment strategies. Future studies should examine long‐term outcomes in NC. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to assess the relationship between baseline caries experience and the restoration replacement rate in children. Methods: The 5-year New England Children's Amalgam Trial recruited 534 6- to 10-year-old children with 2 or more carious posterior teeth. The association between decay and longevity of restorations was assessed. Restorations with no follow-up (N=391) were excluded from analysis. Results: The average follow-up was 3.0±1.6 years in 489 children. Restorations with fallow-up (N=3,604) were placed in mouths with a median of 15 dfs/DFS and 8 dft/DFT The need for replacement increased significantly (P≤.001) with increasing numbers of dfs/DFS and dft/DFT After 5 years of follow-up, at least 15% of restorations in a mouth with ≥14 dfs/DFS needed replacement, compared to 9% for 2 to 5 dfs/DFS. Comparing dft/DFT after 5 years of follow-up, there was a 23% replacement rate far >12 dft/DFT compared to 10% for 2 to 3 dft/DFT Decay in the mouth had a greater association with the need for replacement due to new caries compared to replacement due to recurrent caries. Conclusion: Children with more decay at the time of restoration placement were at higher risk for replacement of restorations. [ABSTRACT FROM AUTHOR]

: This study aims to prospectively examine the trends and reasons for the underutilization of free semiannual preventive dental care provided to children with unmet dental needs who participated in the 5-year New England Children's Amalgam Trial. Children aged 6 to 10 at baseline (1997-99) with ≥ 2 posterior carious teeth were recruited from rural Maine (n = 232) and urban Boston (n = 266). Interviewer-administered questionnaires assessed demographic and personal characteristics. Reasons for missed appointments were recorded during follow-up and are descriptively presented. We used an ordinal logistic regression to analyze the utilization of semiannual dental visits. On average, urban children utilized 69 percent of the visits and rural children utilized 82 percent of the visits. For both sites, utilization steadily decreased until the end of the 5-year trial. Significant predictors of underutilization in the multivariate model for urban children were non-White race, household welfare use, deep debt, and distance to dental clinic. Among the relatively less-diverse rural children, caregiver education level and a greater number of decayed tooth surfaces at baseline (i.e., need for care) were significantly associated with underutilization. Among all children, the common reasons for missed visits included guardian scheduling and transportation difficulties; reasons among urban participants also indicated a low priority for dental care. Among these children with unmet dental needs, the provision of free preventive dental care was insufficient to remove the disparities in utilization and did not consistently result in high utilization through follow-up. Differences between educational levels, ethnicities, and rural/urban location suggest that public health programs need to target the social settings in which financial burdens exist. [ABSTRACT FROM AUTHOR]

Previous research shows increased dental decay among immigrants, but little is known about the oral health of the growing population of children of immigrants. We compared the children of immigrants to the children of US-born caregivers in their caries experience at enrollment and their new caries increments during the 5-year New England Children's Amalgam Trial (NECAT). NECAT recruited 283 Boston-area children aged 6 to 10 with untreated caries and offered free semiannual preventive and restorative dental care during the trial. Sociodemographic factors and caregiver immigrant status were assessed through interviews. Multivariate negative binomial models evaluated the association between caregiver immigrant status and clinically assessed carious surfaces. Forty percent of these Boston-area children had immigrant caregivers. At baseline, the children of immigrants had more carious surfaces (11.5 versus 9.4, adjusted for race/ethnicity, age, gender, and caregiver smoking status). Caregiver language preference explained some of this association. Immigrant status and language preference were not associated with 5-year caries increments. Prevalent disparities in the unmet dental needs of the immigrants' children were quickly ameliorated during participation in NECAT. Dental initiatives that target neighborhoods and are sensitive to acculturation levels may help improve and maintain the oral health of immigrant families. [ABSTRACT FROM AUTHOR]

To compare the prevalence of caries between rural and urban children with unmet dental health needs who participated in the New England Children's Amalgam Trial. Baseline tooth and surface caries were clinically assessed in children from rural Maine ( n = 243) and urban Boston ( n = 291), who were aged 6 to 10 years, with two or more posterior carious teeth and no previous amalgam restorations. Statistical analyses used negative binomial models for primary dentition caries and zero-inflated models for permanent dentition caries. Urban children had a higher mean number of carious primary surfaces (8.5 versus 7.4) and teeth (4.5 versus 3.9) than rural children. The difference remained statistically significant after adjusting for sociodemographic factors and toothbrushing frequency. In permanent dentition, urban children were approximately three times as likely to have any carious surfaces or teeth. However, rural/urban dwelling was not statistically significant in the linear analysis of caries prevalence among children with any permanent dentition caries. Covariates that were statistically significant in all models were age and number of teeth. Toothbrushing frequency was also important for permanent teeth. Within this population of New England children with unmet oral health needs, significant differences were apparent between rural and urban children in the extent of untreated dental decay. Results indicate that families who agree to participate in programs offering reduced cost or free dental care may present with varying amounts of dental need based on geographic location. [ABSTRACT FROM AUTHOR]

Case-control studies indicate that vitamins C, E, A and carotenoids decrease risk of oral premalignant lesions (OPLs) and oral cancer, but clinical trials have failed to find protective effects of β-carotene and suggest that vitamin E may increase risk. The authors prospectively evaluated the association between intake of vitamins C, E, A and carotenoids and incidence of OPL. Participants were 42,340 men in the Health Professionals Follow-up Study who provided information on supplement use and diet every 2-4 years by food frequency questionnaire. The authors confirmed 207 clinically or histopathologically diagnosed OPL events occurring between 1986 and 2002 by medical record review. Multivariate-adjusted relative risks (RR) of OPL were calculated with proportional hazards models. Total intake of vitamin C, vitamin A or carotenoids was not significantly associated with OPL risk. Dietary vitamin C was significantly associated with reduced risk (quintile 5 vs. 1, RR = 0.52, 95% CI 0.31-0.85, p [ABSTRACT FROM AUTHOR]

Background: To identify at‐risk individuals that will likely benefit from disease‐modifying treatment and improve selection for clinical trials, the role of unobjectified cognitive complaints (subjective cognitive decline, SCD) in preclinical Alzheimer's Disease (AD) needs to be refined. Although persons with SCD are at increased risk of developing dementia, it is unclear whether SCD is a symptomatic indicator of preclinical AD. We aim to identify SCD characteristics that are associative of amyloid positivity and are thus indicative of preclinical AD. Methods: We included 1,336 persons with SCD from 14 centers included in the Amyloid Biomarker Study. Amyloid‐ß deposition was measured with positron emission tomography or cerebrospinal‐fluid biomarkers and dichotomized as normal or abnormal according to study‐specific cut‐offs. SCD characteristics included were subjective decline in memory, informant confirmation of SCD, concerns about complaints, feelings of worse performance, subjective decline in attention and concentration, depression, anxiety, and setting. Generalized‐estimating‐equations adjusting for center were used to examine the association between SCD characteristics and amyloid positivity. Results: Average age was 66.5 years, 52% were female, mean education was 14.2 years, 33% was APOE‐ε4 positive, 19% was amyloid positive, 21% was t‐tau positive, and 30% was p‐tau positive. Increased age (p<0.001) and APOE‐ε4 carriership (p<0.001) were associated with a higher probability of amyloid positivity. Subjective decline in memory was associated with an increased probability of amyloid positivity (25% vs. 19% for persons without subjective decline specific to memory, mean difference 9%, p=0.036). The probability of amyloid positivity differed according to setting and was higher in a memory clinic setting (29%) compared to research setting (15%) and population setting (5%). The other SCD characteristics were not associated with amyloid positivity. Age, APOE‐ε4 carriership, subjective decline in memory, and setting remained independent predictors of amyloid positivity when analysed combined. Conclusion: Based on these analyses, age, APOE‐ε4 carriership, subjective decline in memory, and setting are characteristcs that may help identify preclinical AD in persons with SCD. [ABSTRACT FROM AUTHOR]

Objective: To investigate treatment seeking and utilization of women diagnosed with hypoactive sexual desire disorder (HSDD) in the clinical setting., Methods: We used interim baseline data from the ongoing HSDD Registry for Women (n = 724, enrolled at 27 clinical sites across the United States in 2008-2009). The recent diagnosis of generalized, acquired HSDD was confirmed by clinician's administration of the validated diagnostic Decreased Sexual Desire Screener. Treatment-seeking behavior was categorized as formal (discussion with a healthcare provider or use of off-label prescription treatment for HSDD) or informal/none (over-the-counter products, anonymous media, or no help seeking)., Results: Over half (n = 386, 53%) of these women with clinically diagnosed HSDD had not sought formal healthcare for their decreased sexual desire problem. Among formal healthcare seekers, 36% remained untreated, whereas 64% received some form of treatment. The most common treatments reported were nonprescription lubricants or arousal creams (36%) and off-label prescription medications (20%). Women were more likely to have sought formal help if they were married/cohabiting, were postmenopausal, had private health insurance, had > 5 current prescription medications, had depression symptoms, had a longer duration of sexual desire problems, or reported that the partner relationship or sense of femininity/sexual self was threatened by HSDD., Conclusions: In these women with HSDD, less than half had sought healthcare, but of those who had sought healthcare, almost two thirds received some form of treatment. Regardless of treatment-seeking behavior, most women had a strong desire to "feel like a normal person again" regarding sexuality, which was the most common motivating factor for treatment seeking.

Recent case-control studies indicate that alcohol increases the risk of oral premalignant lesions (OPL) among tobacco users, but the independent association between alcohol and OPL remains unclear. We prospectively evaluated the association between alcohol consumption and the incidence of OPL. Participants were 41,458 men in the Health Professionals Follow-up Study. Alcohol consumption was assessed every 4 years using validated food frequency questionnaires. We confirmed clinically or histopathologically diagnosed OPL events occurring between 1986 and 2002 by medical record review (193 cases). Multivariate-adjusted relative risks of OPL were calculated from Cox proportional hazards models. With detailed control for tobacco and other variables, multivariate relative risks (95% confidence intervals) were 1.7 (0.9-3.2) for drinkers of 0.1 to 14.9 g/d, 2.9 (1.5-5.6) for 15 to 29.9 g/d, and 2.5 (1.3-5.1) for > or =30 g/d, compared with nondrinkers. Approximately one additional drink per day (12.5 g) was associated with a 22% increase in risk (P < 0.001). The associations did not vary by beverage type, frequency, or consumption with meals. Results were similar when restricted to cases of oral epithelial dysplasia. Alcohol increased OPL risk in never-users of tobacco as well as in past or current users. An interaction between alcohol and tobacco was apparent by their more-than-additive joint effects. Alcohol is an independent risk factor for OPL, regardless of beverage type or drinking pattern. Recommendations to reduce alcohol intake have the potential to reduce incidence of OPL in nonsmokers and smokers alike.