Cognitively defined Alzheimer's dementia subgroups have distinct atrophy patterns.

INTRODUCTION: We sought to determine structural magnetic resonance imaging (MRI) characteristics across subgroups defined based on relative cognitive domain impairments using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and to compare cognitively defined to imaging-defined subgroups. METHODS: We used data from 584 people with Alzheimer's disease (AD) (461 amyloid positive, 123 unknown amyloid status) and 118 amyloid-negative controls. We used voxel-based morphometry to compare gray matter volume (GMV) for each group compared to controls and to AD-Memory. RESULTS: There was pronounced bilateral lower medial temporal lobe atrophy with relative cortical sparing for AD-Memory, lower left hemisphere GMV for AD-Language, anterior lower GMV for AD-Executive, and posterior lower GMV for AD-Visuospatial. Formal asymmetry comparisons showed substantially more asymmetry in the AD-Language group than any other group (p = 1.15 × 10-10 ). For overlap between imaging-defined and cognitively defined subgroups, AD-Memory matched up with an imaging-defined limbic predominant group. DISCUSSION: MRI findings differ across cognitively defined AD subgroups.

Measurement precision across cognitive domains in the Alzheimer's Disease Neuroimaging Initiative (ADNI) data set.

OBJECTIVE: To demonstrate measurement precision of cognitive domains in the Alzheimer's Disease Neuroimaging Initiative (ADNI) data set. METHOD: Participants with normal cognition (NC), mild cognitive impairment (MCI), and Alzheimer's disease (AD) were included from all ADNI waves. We used data from each person's last study visit to calibrate scores for memory, executive function, language, and visuospatial functioning. We extracted item information functions for each domain and used these to calculate standard errors of measurement. We derived scores for each domain for each diagnostic group and plotted standard errors of measurement for the observed range of scores. RESULTS: Across all waves, there were 961 people with NC, 825 people with MCI, and 694 people with AD at their most recent study visit (data pulled February 25, 2019). Across ADNI's battery there were 34 memory items, 18 executive function items, 20 language items, and seven visuospatial items. Scores for each domain were highest on average for people with NC, intermediate for people with MCI, and lowest for people with AD, with most scores across all groups in the range of -1 to +1. Standard error of measurement in the range from -1 to +1 was highest for memory, intermediate for language and executive functioning, and lowest for visuospatial. CONCLUSION: Modern psychometric approaches provide tools to help understand measurement precision of the scales used in studies. In ADNI, there are important differences in measurement precision across cognitive domains. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

A genome-wide search for pleiotropy in more than 100,000 harmonized longitudinal cognitive domain scores.

BACKGROUND: More than 75 common variant loci account for only a portion of the heritability for Alzheimer's disease (AD). A more complete understanding of the genetic basis of AD can be deduced by exploring associations with AD-related endophenotypes. METHODS: We conducted genome-wide scans for cognitive domain performance using harmonized and co-calibrated scores derived by confirmatory factor analyses for executive function, language, and memory. We analyzed 103,796 longitudinal observations from 23,066 members of community-based (FHS, ACT, and ROSMAP) and clinic-based (ADRCs and ADNI) cohorts using generalized linear mixed models including terms for SNP, age, SNP × age interaction, sex, education, and five ancestry principal components. Significance was determined based on a joint test of the SNP's main effect and interaction with age. Results across datasets were combined using inverse-variance meta-analysis. Genome-wide tests of pleiotropy for each domain pair as the outcome were performed using PLACO software. RESULTS: Individual domain and pleiotropy analyses revealed genome-wide significant (GWS) associations with five established loci for AD and AD-related disorders (BIN1, CR1, GRN, MS4A6A, and APOE) and eight novel loci. ULK2 was associated with executive function in the community-based cohorts (rs157405, P = 2.19 × 10-9). GWS associations for language were identified with CDK14 in the clinic-based cohorts (rs705353, P = 1.73 × 10-8) and LINC02712 in the total sample (rs145012974, P = 3.66 × 10-8). GRN (rs5848, P = 4.21 × 10-8) and PURG (rs117523305, P = 1.73 × 10-8) were associated with memory in the total and community-based cohorts, respectively. GWS pleiotropy was observed for language and memory with LOC107984373 (rs73005629, P = 3.12 × 10-8) in the clinic-based cohorts, and with NCALD (rs56162098, P = 1.23 × 10-9) and PTPRD (rs145989094, P = 8.34 × 10-9) in the community-based cohorts. GWS pleiotropy was also found for executive function and memory with OSGIN1 (rs12447050, P = 4.09 × 10-8) and PTPRD (rs145989094, P = 3.85 × 10-8) in the community-based cohorts. Functional studies have previously linked AD to ULK2, NCALD, and PTPRD. CONCLUSION: Our results provide some insight into biological pathways underlying processes leading to domain-specific cognitive impairment and AD, as well as a conduit toward a syndrome-specific precision medicine approach to AD. Increasing the number of participants with harmonized cognitive domain scores will enhance the discovery of additional genetic factors of cognitive decline leading to AD and related dementias.

Attitudes toward participation in breast cancer randomized clinical trials in the African American community: a focus group study.

Participation of African Americans in research trials is low. Understanding the perspectives of African American patients toward participation in clinical trials is essential to understanding the disparities in participation rates compared with whites. A qualitative study was conducted to discover attitudes of the African American community regarding willingness to participate in breast cancer screening and randomized clinical trials. Six focus groups consisting of 8 to 11 African American women (N = 58), aged 30 to 65, were recruited from local churches. Focus group sessions involved a 2-hour audio-taped discussion facilitated by 2 moderators. A breast cancer randomized clinical trial involving an experimental breast cancer treatment was discussed to identify the issues related to willingness to participate in such research studies. Six themes surrounding willingness to participate in randomized clinical trials were identified: (1) Significance of the research topic to the individual and/or community; (2) level of trust in the system; (3) understanding of the elements of the trial; (4) preference for "natural treatments" or "religious intervention" over medical care; (5) cost-benefit analysis of incentives and barriers; and (6) openness to risk versus a preference for proven treatments. The majority (80%) expressed willingness or open-mindedness to the idea of participating in the hypothetical trial. Lessons learned from this study support the selection of a culturally diverse research staff and can guide the development of research protocols, recruitment efforts, and clinical procedures that are culturally sensitive and relevant.

Current realities of delivering mammography services in the community: do challenges with staffing and scheduling exist?

PURPOSE: To evaluate the current (2001-2002) capacity of community-based mammography facilities to deliver screening and diagnostic services in the United States. MATERIALS AND METHODS: Institutional review board approvals and patient consent were obtained. A mailed survey was sent to 53 eligible mammography facilities in three states (Washington, New Hampshire, and Colorado). Survey questions assessed equipment and staffing availability, as well as appointment waiting times for screening and diagnostic mammography services. Criterion-related content and construct validity were obtained first by means of a national advisory committee of academic, scientific, and clinical colleagues in mammography that reviewed literature on existing surveys and second by pilot testing a series of draft surveys among community mammography facilities not inclusive of the study facilities. The final survey results were independently double entered into a relational database with programmed data checks. The data were sent encrypted by means of file transfer protocol to a central analytical center at Group Health Cooperative. A two-sided P value with alpha = .05 was considered to show statistical significance in all analyses. RESULTS: Forty-five of 53 eligible mammography facilities (85%) returned the survey. Shortages of radiologists relative to the mammographic volume were found in 44% of mammography facilities overall, with shortages of radiologists higher in not-for-profit versus for-profit facilities (60% vs 28% reported). Shortages of Mammography Quality Standards Act-qualified technologists were reported by 20% of facilities, with 46% reporting some level of difficulty in maintaining qualified technologists. Waiting times for diagnostic mammography ranged from less than 1 week to 4 weeks, with 85% performed within 1 week. Waiting times for screening mammography ranged from less than 1 week to 8 weeks, with 59% performed between 1 week and 4 weeks. Waiting times for both diagnostic and screening services were two to three times higher in high-volume compared with low-volume facilities. CONCLUSION: Survey results show shortages of radiologists and certified mammography technologists.

Racial inequities in the timing of breast cancer detection, diagnosis, and initiation of treatment.

BACKGROUND: Recent studies suggest differences in quality and timeliness of care received may be major contributing sources to the racial disparity in breast cancer detection and related outcomes. METHODS: Female patients with breast cancer diagnosed during 1985-1993 (n=400) and followed through June 20, 2001, were included in this retrospective cohort study. Three white patients were selected randomly and matched to each black patient by year of diagnosis. Method and timing of diagnosis and timing of treatment were abstracted from medical records. Initial staging and subsequent breast cancer recurrence and vital status were obtained from the Hospital and Connecticut State Tumor Registry. RESULTS: Black women were more likely than white women to be diagnosed after a patient-noted abnormality. Black women were less likely than white women to have completed a diagnostic evaluation within 30 days after a patient-noted abnormality (P <0.01) or after having an abnormality noted on screening mammogram (P=0.0001) and were less likely to have initiated treatment within 30 days of diagnosis (P=0.0001). Women diagnosed after a patient-noted abnormality were more likely to have subsequent breast cancer recurrence and/or death due to breast cancer compared with women diagnosed after a screening mammogram (56% versus 24%, respectively, P <0.05). CONCLUSIONS: Racial differences were identified at each step in the evaluation and treatment clinical pathway, including method of detection, timing from first symptoms of cancer to pathologic diagnosis, and timing from diagnosis to initiation of treatment. The findings highlight the need to provide equal opportunity for timely medical care and treatment.

Community-based mammography practice: services, charges, and interpretation methods.

OBJECTIVE: The purpose of our study was to accurately describe facility characteristics among community-based screening and diagnostic mammography practices in the United States. MATERIALS AND METHODS: A survey was developed and applied to community-based facilities providing screening mammography in three geographically distinct locations in the states of Washington, Colorado, and New Hampshire. The facility survey was conducted between December 2001 and September 2002. Characteristics surveyed included facility type, services offered, charges for screening and diagnostic mammography, information systems, and interpretation methods, including the frequency of double interpretation. RESULTS: Among 45 responding facilities, services offered included screening mammography at all facilities, diagnostic mammography at 34 facilities (76%), breast sonography at 30 (67%), breast MRI at seven (16%), and nuclear medicine breast scanning at seven (16%). Most facilities surveyed were radiology practices in nonhospital settings. Eight facilities (18%) reported performing clinical breast examinations routinely along with screening mammography. Only five screening sites (11%) used computer-aided detection (CAD) and only two (5%) used digital mammography. Nearly two thirds of facilities interpreted screening mammography examinations on-site, whereas 91% of facilities interpreted diagnostic examinations on-site. Only three facilities (7%) interpreted screening examinations on line as they were performed. Approximately half of facilities reported using some type of double interpretation, although the methods of double interpretation and the fraction of cases double-interpreted varied widely across facilities. On average, approximately 15% of screening examinations and 10% of diagnostic examinations were reported as being double-interpreted. CONCLUSION: Comparison of this survey's results with those collected a decade earlier indicates dramatic changes in the practice of mammography, including a clear distinction between screening and diagnostic mammography, batch interpretation of screening mammograms, and improved quality assurance and medical audit tools. Diffusion of new technologies such as CAD and digital mammography was not widespread. The methods of double-interpretation and the fraction of cases double-interpreted varied widely across study sites.

International variation in screening mammography interpretations in community-based programs.

BACKGROUND: Variations in mammography interpretations may have important clinical and economic implications. To evaluate international variability in mammography interpretation, we analyzed published reports from community-based screening programs from around the world. METHODS: A total of 32 publications were identified in MEDLINE that fit the study inclusion criteria. Data abstracted from the publications included features of the population screened, examination technique, and clinical outcomes, including the percentage of mammograms judged to be abnormal, positive predictive value of an abnormal mammogram (PPV(A)), positive predictive value of a biopsy performed (PPV(B)), and percentages of breast cancer patients with ductal carcinoma in situ (DCIS) and minimal disease (DCIS and/or tumor size < or =10 mm). North American screening programs were compared with those from other countries using meta-regression analysis. All statistical tests were two-sided. RESULTS: Wide ranges were noted for the percentage of mammograms judged to be abnormal (1.2%-15.0%), for PPV(A) (3.4%-48.7%), for PPV(B) (5.0%-85.2%), for percentage diagnosed with DCIS (4.3%-68.1%), and for percentage diagnosed with minimal disease (14.0%-80.6%). The percentage of mammograms judged to be abnormal were 2-4 percentage points higher in North American screening programs than they were in programs from other countries, after adjusting for covariates such as percentage of women who were less than 50 years of age and calendar year in which the mammogram was performed. The percentage of mammograms judged to be abnormal had a negative association with PPV(A) and PPV(B) (both P<.001) and a positive association with the frequency of DCIS cases diagnosed (P =.008) and the number of DCIS cases diagnosed per 1000 screens (P =.024); no consistent relationship was observed with the proportion of breast cancer diagnoses reported as having minimal disease or the number of minimal disease cases diagnosed per 1000 screens. CONCLUSION: North American screening programs appear to interpret a higher percentage of mammograms as abnormal than programs from other countries without evident benefit in the yield of cancers detected per 1000 screens, although an increase in DCIS detection was noted.

Asian American and Pacific Islander seafood consumption -- a community-based study in King County, Washington.

This paper describes and quantifies seafood consumption rates, and acquisition and preparation habits of 202 first- and second-generation Asian American and Pacific Islanders (AAPI) from 10 ethnic groups (Cambodian, Chinese, Filipino, Hmong, Japanese, Korean, Laotian, Mien, Samoan, and Vietnamese) in King County, Washington in 1997. Participants were all seafood consumers. Average and median seafood consumption rates were 117.2 and 89 g/day, respectively, based on the average body weight (62 kg) of participants. Shellfish comprised 45.9% and "all finfish" 43.3% of all seafood consumed. Consumption rates varied significantly between ethnic groups with Vietnamese (2.63 g/kg/day) and Japanese (2.18 g/kg/day) having the highest average consumption rates, and Mien (0.58 g/kg/day) and Hmong (0.59 g/kg/day) the lowest. The most frequently consumed finfish and invertebrates were salmon (93% of respondents), tuna (86%), shrimp (98%), crab (96%), and squid (82%). Fish fillets were eaten with the skin 55%, and the head, bones, eggs, and/or other organs 20% of the time. Crabmeat including the hepatopancreas (accumulates lipophilic chemicals such as organochlorine compounds) was consumed 43% of the time. This paper was a product of a Community-University Partnership. Community guidance in study design and data collection was essential for successful participation by the AAPI Community. Data reported here not only will provide risk assessors with AAPI-specific seafood consumption rates but with insights into cultural consumption/acquisition habits that may alter risk assessment assumptions for the AAPI Community.

The personal costs and convenience of screening mammography.

BACKGROUND: Few studies have examined the impact of women's personal costs on obtaining a screening mammogram in the United States. METHODS: All women obtaining screening mammograms at nine Connecticut mammography facilities during a 2-week study period were asked to complete a questionnaire. Facilities included urban and rural fixed sites and mobile sites. The survey included questions about insurance coverage, mammogram payment, and personal costs in terms of transportation, family care, parking, and lost work time from the women's perspective. RESULTS: The response rate was 62% (731 of 1189). Thirty-two percent of respondents incurred some type of personal cost, including lost work time, family care, and parking. Women incurring personal costs were more likely than those without personal costs to attend an urban facility (46% vs. 23%, p < 0.01) and be under the age of 50 (40% vs. 26%, p < 0.01). Overall, 61% of women listed convenience and 17% listed cost as a reason for choosing a mammography facility; 23% reported that cost might prevent them from obtaining a future mammogram. CONCLUSIONS: One third of women obtaining mammograms may be incurring personal costs. These personal costs should be considered in future cost-effectiveness analyses.