Examining the benefits and harms of Alzheimer's disease screening for family members of older adults: study protocol for a randomized controlled trial

BACKGROUND: Multiple national expert panels have identified early detection of Alzheimer's disease and related dementias (ADRD) as a national priority. However, the United States Preventive Services Task Force (USPSTF) does not currently support screening for ADRD in primary care given that the risks and benefits are unknown. The USPSTF stresses the need for research examining the impact of ADRD screening on family caregiver outcomes. METHODS: The Caregiver Outcomes of Alzheimer's Disease Screening (COADS) is a randomized controlled trial that will examine the potential benefits or harms of ADRD screening on family caregivers. It will also compare the effectiveness of two strategies for diagnostic evaluation and management after ADRD screening. COADS will enroll 1800 dyads who will be randomized into three groups (n = 600/group): the 'Screening Only' group will receive ADRD screening at baseline and disclosure of the screening results, with positive-screen participants receiving a list of local resources for diagnostic follow-up; the 'Screening Plus' group will receive ADRD screening at baseline coupled with disclosure of the screening results, with positive-screen participants referred to a dementia collaborative care program for diagnostic evaluation and potential care; and the control group will receive no screening. The COADS trial will measure the quality of life of the family member (the primary outcome) and family member mood, anxiety, preparedness and self-efficacy (the secondary outcomes) at baseline and at 6, 12, 18 and 24 months. Additionally, the trial will examine the congruence of depressive and anxiety symptoms between older adults and family members at 6, 12, 18 and 24 months and compare the effectiveness of two strategies for diagnostic evaluation and management after ADRD screening between the two groups randomized to screening (Screening Only versus Screening Plus). DISCUSSION: We hypothesize that caregivers in the screening arms will express higher levels of health-related quality of life, lower depressive and anxiety symptoms, and better preparation for caregiving with higher self-efficacy at 24 months. Results from this study will directly inform the National Plan to Address Alzheimer's Disease, the USPSTF and other organizations regarding ADRD screening and early detection policies

Acceptability and Results of Dementia Screening Among Older Adults in the United States

OBJECTIVES: To measure older adults acceptability of dementia screening and assess screening test results of a racially diverse sample of older primary care patients in the United States. DESIGN: Cross-sectional study of primary care patients aged 65 and older. SETTING: Urban and suburban primary care clinics in Indianapolis, Indiana, in 2008 to 2009. PARTICIPANTS: Nine hundred fifty-four primary care patients without a documented diagnosis of dementia. MEASUREMENTS: Community Screening Instrument for Dementia, the Mini-Mental State Examination, and the Telephone Instrument for Cognitive Screening. RESULTS: Of the 954 study participants who consented to participate, 748 agreed to be screened for dementia and 206 refused screening. The overall response rate was 78.4%. The positive screen rate of the sample who agreed to screening was 10.2%. After adjusting for demographic differences the following characteristics were still associated with increased likelihood of screening positive for dementia: age, male sex, and lower education. Patients who believed that they had more memory problems than other people of their age were also more likely to screen positive for dementia. CONCLUSION: Age and perceived problems with memory are associated with screening positive for dementia in primary care

Screening, referral, and participation in a weight management program implemented in five CHCs

Community health centers have the potential to lessen obesity. We conducted a retrospective evaluation of a quality improvement program that included electronic body mass index (BMI) screening with provider referral to an in-clinic lifestyle behavior change counselor with weekly nutrition and exercise classes. There were 26,661 adult patients seen across five community health centers operating the weight management program. There were 23,593 (88%) adult patients screened, and 12,487 (53%) of these patients were overweight or obese (BMI >or=25). Forty percent received a provider referral, 15.6% had program contact, and 2.1% had more than 10 program contacts. A mean weight loss of seven pounds was observed among those patients with more than 10 program contacts. No significant weight change was observed in patients with less contact. Achieving public health impact from guideline recommended approaches to CHC-based weight management will require considerable improvement in patient and provider participation

Patient characteristics associated with screening positive for Alzheimer's disease and related dementia

Introduction: Screening all older adults for Alzheimer's disease and related dementias (ADRD) in primary care may not be acceptable or feasible. The goal of this study was to identify factors that could optimize screening in primary care and enhance its feasibility. Methods: This is a cross-sectional study in rural, suburban, and urban primary care practices in Indiana. A total of 1,723 patients ≥65 years of age were screened for ADRD using the Memory Impairment Screen. Logistic regression was used to identify patient-specific factors associated with screening positive for ADRD. Results: The positive screening rate was 4.9%. Rates varied significantly across the three study sites. The rural site had the lowest rate (2.8%), which was significantly lower than the rates at the suburban (5.6%) and urban (6.6%) sites (P<0.01). Patient age, sex, and education were significantly (P<0.05) associated with screening positive for ADRD. Conclusion: Targeted screening of patients at risk for ADRD may represent a more optimal and feasible screening alternative to population screening

Traits of patients who screen positive for dementia and refuse diagnostic assessment

BACKGROUND: As part of the debate about screening for dementia, it is critical to understand why patients agree or disagree to diagnostic assessment after a positive screening test. We used the Perceptions Regarding Investigational Screening for Memory in Primary Care (PRISM-PC) questionnaire to measure the characteristics of patients who screened positive for dementia but refused further diagnostic assessment. METHODS: Survey of patients ≥65 years old without a diagnosis of dementia attending primary care clinics in Indianapolis, IN, in 2008 and 2009. RESULTS: Five hundred and fifty-four individuals completed the PRISM-PC and 63 screened positive. Of those, 21 (33%) accepted and 42 (67%) refused diagnostic assessment. In adjusted models, having larger stigma domain scores and living alone were significantly associated with increased odds of refusing the diagnostic assessment. CONCLUSION: Despite screening positive, many patients refused a diagnostic assessment. Living alone and the perceived stigmas of dementia are associated with the refusal of diagnostic assessment for dementia

Organotopic organization of the porcine mid-cervical vagus nerve

Introduction: Despite detailed characterization of fascicular organization of somatic nerves, the functional anatomy of fascicles evident in human and large mammal cervical vagus nerve is unknown. The vagus nerve is a prime target for intervention in the field of electroceuticals due to its extensive distribution to the heart, larynx, lungs, and abdominal viscera. However, current practice of the approved vagus nerve stimulation (VNS) technique is to stimulate the entire nerve. This produces indiscriminate stimulation of non-targeted effectors and undesired side effects. Selective neuromodulation is now a possibility with a spatially-selective vagal nerve cuff. However, this requires the knowledge of the fascicular organization at the level of cuff placement to inform selectivity of only the desired target organ or function. / Methods and results: We imaged function over milliseconds with fast neural electrical impedance tomography and selective stimulation, and found consistent spatially separated regions within the nerve correlating with the three fascicular groups of interest, suggesting organotopy. This was independently verified with structural imaging by tracing anatomical connections from the end organ with microCT and the development of an anatomical map of the vagus nerve. This confirmed organotopic organization. / Discussion: Here we show, for the first time, localized fascicles in the porcine cervical vagus nerve which map to cardiac, pulmonary and recurrent laryngeal function (N = 4). These findings pave the way for improved outcomes in VNS as unwanted side effects could be reduced by targeted selective stimulation of identified organ-specific fiber-containing fascicles and the extension of this technique clinically beyond the currently approved disorders to treat heart failure, chronic inflammatory disorders, and more

Risks and benefits of screening for dementia in primary care: the IU CHOICE trial

Background/objective: The benefits and harms of screening of Alzheimer disease and related dementias (ADRDs) are unknown. This study addressed the question of whether the benefits outweigh the harms of screening for ADRDs among older adults in primary care. Design, setting, and participants: Single-blinded, two-arm, randomized controlled trial (October 2012-September 2016) in urban, suburban, and rural primary care settings in Indiana. A total of 4005 primary care patients (aged ≥65 years) were randomized to ADRD screening (n = 2008) or control (n = 1997). Intervention: Patients were screened using the Memory Impairment Screen or the Mini-Cog and referred for a voluntary follow-up diagnostic assessment if they screened positive on either or both screening tests. Measurements: Primary measures were health-related quality of life (HRQOL; Health Utilities Index) at 12 months, depressive symptoms (Patient Health Questionnaire-9), and anxiety symptoms (Generalized Anxiety Disorder seven-item scale) at 1 month. Results: The mean age was 74.2 years (SD = 6.9 years); 2257 (66%) were female and 2301 (67%) were white. At 12 months, we were unable to detect differences in HRQOL between the groups (effect size = 0.009 [95% confidence interval {CI} = -0.063 to 0.080]; P = .81). At 1 month, differences in mean depressive symptoms (mean difference = -0.23 [90% CI = -0.42 to -0.039]) and anxiety symptoms (mean difference = -0.087 [90% CI = -0.246 to 0.072]) were within prespecified equivalency range. Scores for depressive and anxiety symptoms were similar between the groups at all time points. No differences in healthcare utilization, advance care planning, and ADRD recognition by physicians were detected at 12 months. Conclusion: We were unable to detect a difference in HRQOL for screening for ADRD among older adults. We found no harm from screening measured by symptoms of depression or anxiety. Missing data, low rates of dementia detection, and high rate of refusal for follow-up diagnostic assessments after a positive screen may explain these findings. J Am Geriatr Soc 68:535-543, 2020

A global role for KLF1 in erythropoiesis revealed by ChIP-seq in primary erythroid cells

KLF1 regulates a diverse suite of genes to direct erythroid cell differentiation from bipotent progenitors. To determine the local cis-regulatory contexts and transcription factor networks in which KLF1 operates, we performed KLF1 ChIP-seq in the mouse. We found at least 945 sites in the genome of E14.5 fetal liver erythroid cells which are occupied by endogenous KLF1. Many of these recovered sites reside in erythroid gene promoters such as Hbb-bl, but the majority are distant to any known gene. Our data suggests KLF1 directly regulates most aspects of terminal erythroid differentiation including production of alpha- and beta-globin protein chains, heme biosynthesis, coordination of proliferation and anti-apoptotic pathways, and construction of the red cell membrane and cytoskeleton by functioning primarily as a transcriptional activator. Additionally, we suggest new mechanisms for KLF1 cooperation with other transcription factors, in particular the erythroid transcription factor GATA1, to maintain homeostasis in the erythroid compartment