Impaired Kidney Function, Cerebral Small Vessel Disease and Cognitive Disorders: The Framingham Heart Study.

BACKGROUND AND HYPOTHESIS: It remains unclear if the relation of chronic kidney disease (CKD) with cognitive dysfunction is independent of blood pressure (BP). We evaluated kidney function in relation to premorbid BP measurements, cerebral small vessel disease (CSVD) and incident mild cognitive impairment (MCI) and dementia in Framingham Offspring Cohort participants. METHODS: We included Framingham Offspring participants free of dementia, attending an examination during midlife (exam cycle 6, baseline) for ascertainment of kidney function status, with brain MRI late in life (exam cycles 7-9), cognitive outcome data and available interim hypertension and blood pressure assessments. We related CKD (estimated glomerular filtration rate < 60 ml/min/1.73m2) and albuminuria (urine albumin-to-creatinine ratio ≥ 30 mg/g) to CSVD markers and cognitive outcomes using multivariable regression analyses. RESULTS: Among 2604 participants (mean age 67.4 ± 9.2, 64% women, 7% had CKD and 9% albuminuria), albuminuria was independently associated with covert infarcts (adjusted OR, 1.55 [1.00-2.38]; P = 0.049) and incident MCI and dementia (adjusted HR, 1.68 [1.18-2.41]; P = 0.005 and 1.71, [1.11-2.64]; P = 0.015, respectively). CKD was not associated with CSVD markers but was associated with higher risk of incident dementia (HR, 1.53 [1.02-2.29]; P = 0.041), While albuminuria was predictive of the Alzheimer's disease subtype (Adjusted HR = 1.68, [1.03-2.74]; P = 0.04), CKD was predictive of vascular dementia (Adjusted HR, 2.78, [1.16-6.68]; P = 0.023). CONCLUSIONS: Kidney disease was associated with CSVD and cognitive disorders in asymptomatic community dwelling participants. The relation was independent of premorbid BP, suggesting that the link between kidney and brain disease may involve additional mechanisms beyond blood pressure related injury.

Association of Apolipoprotein E ɛ4 Allele with Enlarged Perivascular Spaces.

OBJECTIVE: Enlarged perivascular spaces have emerged as markers of cerebral small vessel disease and are linked to perivascular drainage dysfunction. The apolipoprotein E-ɛ4 (APOE-ɛ4) allele is the strongest genetic risk factor for cerebral amyloid angiopathy and Alzheimer's neuropathology, but the underlying mechanisms remain unclear. We studied the relationship between APOE-ɛ4 and the topography and burden of enlarged perivascular spaces to elucidate underlying mechanisms between APOE-ɛ4 and adverse clinical outcomes. METHODS: We included 3,564 Framingham Heart Study participants with available genotypes and magnetic resonance imaging. Enlarged perivascular spaces in the basal ganglia and centrum semiovale were rated using a validated scale. We related APOE-ɛ4 allele presence to high burden of enlarged perivascular spaces in each region and a mixed score reflecting high burden in both regions using multivariable logistic regression. Exploratory analyses incorporated presence of cerebral microbleeds and assessed effect modification by hypertension. RESULTS: Mean age was 60.7 years (SD = 14.6), 1,644 (46.1%) were men, 1,486 (41.8%) were hypertensive, and 836 (23.5%) participants were APOE-ɛ4 carriers. APOE-ɛ4 was associated with high burden of enlarged perivascular spaces in the centrum semiovale (odds ratio [OR] = 1.45, 95% confidence interval [CI] = 1.16, 1.81) and mixed regions (OR = 1.37, 95% CI = 1.11, 1.68). Associations were slightly stronger in hypertensive subjects. INTERPRETATION: The APOE-ɛ4 allele plays a modest role in the burden of enlarged perivascular spaces in the centrum semiovale. Further studies are needed to clarify the underlying small vessel disease type in community-dwelling individuals with predominant centrum semiovale enlarged perivascular spaces, which may be hypertensive angiopathy in our sample. ANN NEUROL 2022;92:23-31.

Yoga Versus Education for Veterans with Chronic Low Back Pain: a Randomized Controlled Trial.

BACKGROUND: Yoga is effective for chronic low back pain (cLBP) in civilians but understudied among Veterans. OBJECTIVE: Determine whether yoga is more effective than an educational book for improving disability and pain among Veterans with cLBP. DESIGN, SETTING, AND PARTICIPANTS: Veterans diagnosed with cLBP at a VA medical center enrolled in a randomized controlled trial from March to December of 2015. INTERVENTIONS: Twelve weekly hatha yoga classes or education using The Back Pain Helpbook. MEASURES: Co-primary outcomes were changes from baseline at 12 weeks in back-related disability on the modified Roland Morris Disability Questionnaire and pain on the Defense & Veterans Pain Rating Scale. Secondary outcomes were global improvement, patient satisfaction, pain medication use, and post-traumatic stress symptoms. An intention-to-treat approach was used in primary analyses. RESULTS: One hundred twenty Veterans (mean age, 55.5 [SD = 16.9]; 11 [9%] women; mean number of chronic conditions, 5.5) were randomized to yoga (n = 62) and education (n = 58). At 12 weeks, reductions in back-related disability in yoga (mean difference [MD] = - 3.50, 95% CI: - 5.03, - 1.97) were not significantly different than education (MD = - 2.55, 95% CI: - 4.10, - 0.99; between-group difference: - 0.95 [95% CI: - 3.14, 1.23], p = 0.39). For pain, there was no significant difference between yoga (MD = - 1.01, 95% CI: - 1.67, - 0.35) and education (MD = - 0.81, 95% CI: - 1.36, - 0.27; between-group difference: - 0.20, 95% CI: - 1.06, 0.66, p = 0.65). More yoga than education participants reported being very much or extremely improved (39% vs 19%, OR = 3.71, 95% CI: 1.37, 10.02, p = 0.01) and very satisfied with treatment (60% vs 31%, OR = 4.28, 95% CI: 1.70, 10.77, p = 0.002). No differences in pain medication use or post-traumatic stress symptoms were observed at 12 weeks. No serious adverse events were reported in either group. CONCLUSION: Twelve weekly yoga classes were not more effective than an education intervention for improving pain or disability outcomes among mostly older male Veterans with cLBP and multiple comorbid health conditions. GOV IDENTIFIER: NCT02224183.

Effects by educational attainment of a mammography screening patient decision aid for women aged 75 years and older.

BACKGROUND: To help inform screening decisions, a mammography screening decision aid (DA) for women aged 75 years and older was tested in a cluster randomized clinical trial of 546 women. DA use increased women's knowledge of the benefits and harms of mammography and lowered screening rates. In the current study, the objective was to examine whether participants' views of the DA and/or its effects differed by educational attainment. METHODS: A secondary analysis was conducted of 283 women who received the DA before a personal care provider (PCP) visit during the trial to examine the acceptability of the DA and its effects on knowledge of the benefits and harms of mammography, screening intentions, and receipt of screening by educational attainment. Adjusted analyses accounted for clustering by PCP. RESULTS: Of the 283 participants, 43% had a college education or less. Regardless of educational attainment, 87.2% found the DA helpful. Women with lower educational attainment were less likely to understand all of the DA's content (46.3% vs 67.5%; P < .001), had less knowledge of the benefits and harms of mammography (adjusted mean ± standard error knowledge score, 7.1 ± 0.3 vs 8.1 ± 0.3; P < .001), and were less likely to lower screening intentions (adjusted percentage, 11.4% vs 19.4%; P = .01). Receipt of screening did not differ by educational attainment. CONCLUSIONS: A mammography DA for women aged 75 years and older was helpful to women regardless of their educational attainment; however, those with a college degree or greater understood the DA and, possibly as a result, lowered their screening intentions. Future studies need to examine how to better support informed decision making around mammography screening in older women with lower educational attainment. LAY SUMMARY: The authors examined data from a previous study to learn the effects of a mammography decision aid (DA) for women aged 75 years and older according to their level of education. Overall, women found the DA helpful, but women with lower educational attainment found it harder to understand the benefits and harms of mammography screening and were less likely to lower their screening intentions than women with a college degree. The findings suggest that women aged 75 years and older who have lower educational attainment may need an even lower literacy DA and/or more support from health care professionals.

Exploring Tai Chi Exercise and Mind-Body Breathing in Patients with COPD in a Randomized Controlled Feasibility Trial.

In this pilot feasibility randomized controlled trial, participants with moderate to severe COPD were randomized to a 12-week tai chi or MBB intervention. Participants were assessed at baseline, 12 weeks, and 24 weeks. Feasibility, as assessed by intervention adherence, was the primary outcome. We also estimated preliminary between-group differences in COPD symptoms and health-related quality of life, cognitive-emotional function, and functional status across three timepoints: baseline, 12, and 24 weeks. A total of 92 participants were randomized 2:1 to tai chi (n = 61) or MBB (n = 31). The overall group adherence in the first 12 weeks was 62% in tai chi and 75% in MBB. From baseline to 12 weeks, tai chi demonstrated greater improvements in depressive symptoms (Cohen's d effect size (ES) = -.53; adj mean diff = -2.31 [-5.7, 1.07]), 6-minute walk test distance (ES = .47; adj mean diff = 62.04 [2.85, 121.22]), social support (ES = .36; adj mean diff = .19 [-0.11, 0.49]) and chair stand (ES = .44; adj mean diff = .91 [-0.05, 1.86]). Only improvements in social support were maintained at 24-week follow-up. Tai chi and MBB are feasible for individuals with COPD. Preliminary effects suggest that while our mindful breathing intervention may not be sufficient to impact outcomes, tai chi may result in short-term benefits in mood, social support and functional capacity. More work is needed to better understand mindful breathing for COPD and to examine methods for maintaining improvements from tai chi over time.Supplemental data for this article is available online at https://doi.org/10.1080/15412555.2021.1928037 .

Scripts and Strategies for Discussing Stopping Cancer Screening with Adults > 75 Years: a Qualitative Study.

BACKGROUND: Despite guidelines recommending not to continue cancer screening for adults > 75 years old, especially those with short life expectancy, primary care providers (PCPs) feel ill-prepared to discuss stopping screening with older adults. OBJECTIVE: To develop scripts and strategies for PCPs to use to discuss stopping cancer screening with adults > 75. DESIGN: Qualitative study using semi-structured interview guides to conduct individual interviews with adults > 75 years old and focus groups and/or individual interviews with PCPs. PARTICIPANTS: Forty-five PCPs and 30 patients > 75 years old participated from six community or academic Boston-area primary care practices. APPROACH: Participants were asked their thoughts on discussions around stopping cancer screening and to provide feedback on scripts that were iteratively revised for PCPs to use when discussing stopping mammography and colorectal cancer (CRC) screening. RESULTS: Twenty-one (47%) of the 45 PCPs were community based. Nineteen (63%) of the 30 patients were female, and 13 (43%) were non-Hispanic white. PCPs reported using different approaches to discuss stopping cancer screening depending on the clinical scenario. PCPs noted it was easier to discuss stopping screening when the harms of screening clearly outweighed the benefits for a patient. In these cases, PCPs felt more comfortable being more directive. When the balance between the benefits and harms of screening was less clear, PCPs endorsed shared decision-making but found this approach more challenging because it was difficult to explain why to stop screening. While patients were generally enthusiastic about screening, they also reported not wanting to undergo tests of little value and said they would stop screening if their PCP recommended it. By the end of participant interviews, no further edits were recommended to the scripts. CONCLUSIONS: To increase PCP comfort and capability to discuss stopping cancer screening with older adults, we developed scripts and strategies that PCPs may use for discussing stopping cancer screening.

Hypertension Trends and White Matter Brain Injury in the Offspring Framingham Heart Study Cohort.

BACKGROUND: Hypertension is the most potent stroke risk factor and is also related to cerebral small vessel disease. We studied the relation between mid-to-late-life hypertension trends and cerebral white matter injury in community-dwelling individuals from the FHS (Framingham Heart Study). METHODS: FHS Offspring cohort participants with available mid-life and late-life blood pressure measurements and brain magnetic resonance imaging were included. Multiple regression analyses were used to relate hypertension trends (normotension-normotension [reference], normotension-hypertension, and hypertension-hypertension) to white matter injury metrics on diffusion tensor imaging (free water, fractional anisotropy, and peak skeletonized mean diffusivity) and Fluid Attenuated Inversion Recovery (white matter hyperintensity volume) by different blood pressure cutoffs (130/80, 140/90, and 150/90 mm Hg). RESULTS: We included 1018 participants (mean age 47.3±7.4 years at mid-life and 73.2±7.3 at late-life). At the 140/90 mm Hg cutoff, the hypertension-hypertension trend was associated with higher free water (ß, 0.16 [95% CI, 0.03-0.30]; P=0.021) and peak skeletonized mean diffusivity (ß, 0.15 [95% CI, 0.01-0.29]; P=0.033). At a 130/80 mm Hg cutoff, the hypertension-hypertension trend had significantly higher free water (ß, 0.16 [95% CI, 0.01-0.30]; P=0.035); and the normotension-hypertension (ß, 0.24 [95% CI, 0.03-0.44]; P=0.027) and hypertension-hypertension (ß, 0.22 [95% CI, 0.04-0.41]; P=0.022) trends had significantly increased white matter hyperintensity volume. Exploratory stratified analysis showed effect modifications by APOE ɛ4 allele and age. CONCLUSIONS: Mid-to-late-life hypertension exposure is significantly associated with microstructural and to a lesser extent, visible white matter injury; the effects are observed at both conventional and lower blood pressure cutoffs and are associated with longer duration of hypertension.

Inflammatory biomarkers and MRI visible perivascular spaces: The Framingham Heart Study.

We studied the association between inflammatory biomarkers and magnetic resonance imaging (MRI) visible perivascular spaces (PVS) in Framingham Heart Study participants free of stroke and dementia. PVS in the basal ganglia (BG) and centrum semiovale (CSO) were rated with validated methods and categorized based on counts. A mixed score of high PVS burden in neither, one or both regions was also evaluated. We related biomarkers representing various inflammatory mechanisms to PVS burden using multivariable ordinal logistic regression analysis accounting for vascular risk factors and other MRI markers of cerebral small vessel disease. Among 3604 participants (mean age 58±13 years, 47% males), significant associations were observed for intercellular adhesion molecule1, fibrinogen, osteoprotegerin, and P-selectin in relation to BG PVS, P-selectin for CSO PVS, and tumor necrosis factor receptor 2, osteoprotegerin and cluster of differentiation 40 ligand for mixed topography PVS. Therefore, inflammation may have a role in the pathogenesis of cerebral small vessel disease and perivascular drainage dysfunction represented by PVS, with different and shared inflammatory biomarkers depending on PVS topography.

MRI Visible Perivascular Spaces and the Risk of Incident Mild Cognitive Impairment in a Community Sample.

BACKGROUND: Magnetic resonance imaging (MRI) visible perivascular spaces (PVS) are associated with the risk of incident dementia but their association with the early stages of cognitive impairment remains equivocal. OBJECTIVE: We examined the association between MRI visible PVS and the risk of incident mild cognitive impairment (MCI) in the community-based Framingham Heart Study (FHS). METHODS: FHS participants aged at least 50 years free of stroke, cognitive impairment, and dementia at the time of MRI were included. PVS were rated according to severity in the basal ganglia and centrum semiovale (CSO) using established criteria. Cox regression analyses were used to relate PVS to incident MCI adjusted for demographic and cardiovascular variables. RESULTS: The mean age of the sample (1,314 participants) at MRI was 68 years (SD, 9; 54% women). There were 263 cases of incident MCI over a median 7.4 years follow-up (max, 19.8 years). MCI risk increased with higher PVS severity in the CSO. Relative to persons with the lowest severity rating, persons with the highest severity rating in the CSO had a higher risk of incident MCI (hazard ratio [HR] = 2.55; 95% confidence interval [CI], 1.48-4.37; p = 0.0007). In secondary analysis, this association seemed stronger in women. Risk of incident MCI was nominally higher for participants with the highest severity grade of PVS in the basal ganglia, though not statistically significant relative to the lowest grade (HR = 2.19; 95% CI, 0.78-6.14; p = 0.14). CONCLUSIONS: PVS burden in the CSO may be a risk marker for early cognitive impairment.

Relation of MRI-Visible Perivascular Spaces and Other MRI Markers of Cerebral Small Vessel Disease.

Perivascular spaces (PVS) visible on brain MRI signal cerebral small vessel disease (CSVD). The coexistence of PVS with other CSVD manifestations likely increases the risk of adverse neurological outcomes. We related PVS to other CSVD manifestations and brain volumes that are markers of vascular brain injury and neurodegeneration. Framingham Heart Study (FHS) participants with CSVD ratings on brain MRI were included. PVS were rated in the basal ganglia (BG) and centrum semiovale (CSO) into grades I-IV and a category reflecting high burden in single or mixed CSO-BG regions. We related PVS to covert brain infarcts (CBI), white matter hyperintensities (WMH), cerebral microbleeds (CMB), total brain, hippocampal, and cortical gray matter volumes using adjusted multivariable regression analyses. In 2454 participants (mean age 54 ± 12 years), we observed that higher PVS burden in both BG and CSO was related to CMB in lobar and deep brain regions and increased WMH. Greater CSO PVS burden was associated with decreased total cortical gray volumes. PVS are associated with ischemic markers of CSVD and neurodegeneration markers. Further studies should elucidate the causality between PVS and other CSVD manifestations.

Association of MRI Visible Perivascular Spaces and Neurofilament Light Chain: The Framingham Heart Study.

BACKGROUND: Neurofilament light chain (NfL) is a marker of neuronal injury. Perivascular spaces (PVS) visible on magnetic resonance imaging (MRI) represent cerebral small vessel disease (CSVD) but their role as markers of neuronal injury needs further clarification. OBJECTIVE: To relate PVS burden according to brain topography and plasma NfL. METHODS: Framingham Heart Study (FHS) participants with brain MRI and NfL measurements were included. PVS were rated in the basal ganglia (BG) and centrum semiovale (CSO) using validated methods and categorized based on counts. A mixed region variable representing high burden PVS in either BG or CSO was assessed. Multivariable linear regression analyses were used to relate PVS burden to log-transformed NfL levels in models adjusted for age, sex, FHS cohort, time between MRI and clinic exam, and image view (model 1), vascular risk factors (model 2), and white matter hyperintensity volume, covert brain infarcts, and cerebral microbleeds (model 3). RESULTS: Among 1,457 participants (68.1±8.5 years, 45% males), NfL levels increased with higher PVS burden. Multivariable analysis showed an association of high PVS burden strictly in BG with NfL (ß= 0.117, 95% CI 0.014-0.221; p = 0.027), but attenuated in model 3. The associations were mainly in participants≥65 years (ß= 0.122, 95% CI 0.015-0.229, p = 0.026), women (ß= 0.156, 95% CI 0.024-0.288, p = 0.021), and APOE ɛ4 non-carriers (ß= 0.140, 95% CI 0.017-0.263, p = 0.026). CONCLUSIONS: The association of strictly BG high PVS burden with NfL suggests a role for PVS as markers of neuroaxonal injury, but our results are hypothesis generating and require further replication.

MRI Visible Perivascular Spaces and Risk of Incident Dementia: The Framingham Heart Study.

BACKGROUND AND OBJECTIVES: Perivascular spaces (PVS) visible on magnetic resonance imaging (MRI) scans may represent key aspects in the pathophysiology of stroke and dementia, including cerebral small vessel disease and glymphatic dysfunction. This study aimed to determine the association between MRI-visible PVS burden and the risk of incident dementia. METHODS: The study included community-dwelling Framingham Heart Study Original and Offspring cohort participants with available brain MRI-PVS ratings, free of stroke and dementia. Multivariable Cox proportional hazards regression was used to obtain hazard ratios (HR) and 95% confidence intervals (CI) of the association between MRI-visible PVS and incident dementia. PVS were rated using validated methods in the basal ganglia (BG) and centrum semiovale (CSO). The outcomes included all-cause dementia, Alzheimer's dementia (AD), and vascular dementia. RESULTS: 1449 participants 50 years of age or older (46% male) were included. Over a median follow-up period of 8.3 years, the incidence of all-cause dementia, AD, and vascular dementia was 15.8%, 12.5% and 2.5%, respectively. In models that adjusted for vascular risk factors and cardiovascular disease, the hazard for dementia increased steadily as PVS burden increased, rising two-fold for those with grade II PVS (HR 2.44, 95% CI 1.51 - 3.93) to five-fold in participants with grade IV (HR 5.05, 95% CI 2.75 - 9.26) compared to grade I PVS in CSO. In the BG, hazards increased 1.6-fold (HR 1.62, 95% CI 1.15 - 2.27) for grade II to 2.6-fold (HR 2.67, 95% CI 1.04 - 6.88) for grade IV compared to grade I PVS. The association remained significant for CSO but not for BG, after adjustment for white matter hyperintensity volume, covert infarcts and total brain volume. Similar findings were observed for AD, but vascular dementia, limited by small number of events, was not statistically significant. DISCUSSION: Higher burden of PVS in CSO was associated with increased risk of developing dementia, independent of vascular risk factors, Total brain and white matter hyperintensity volumes and covert infarcts. This finding supports a role for PVS as a subclinical MRI marker to identify individuals in subclinical stages at high risk of developing dementia who may benefit from early intervention.

Strategies for discussing long-term prognosis when deciding on cancer screening for adults over age 75.

BACKGROUND: Consideration of older adults' 10-year prognosis is necessary for high-quality cancer screening decisions. However, few primary care providers (PCPs) discuss long-term (10-year) prognosis with older adults. METHODS: To learn PCPs' and older adults' perspectives on and to develop strategies for discussing long-term prognosis in the context of cancer screening decisions, we conducted qualitative individual interviews with adults 76-89 and focus groups or individual interviews with PCPs. We recruited participants from 4 community and 2 academic Boston-area practices and completed a thematic analysis of participant responses to open-ended questions on discussing long-term prognosis. RESULTS: Forty-five PCPs (21 community-based) participated in 7 focus groups or 7 individual interviews. Thirty patients participated; 19 (63%) were female, 13 (43%) were non-Hispanic Black, and 13 (43%) were non-Hispanic white. Patients and PCPs had varying views on the utility of discussing long-term prognosis. "For some patients and for some families having this information is really helpful," (PCP participant). Some participants felt that prognostic information could be helpful for future planning, whereas others thought the information could be anxiety-provoking or of "no value" because death is unpredictable; still others were unsure about the value of these discussions. Patients often described thinking about their own prognosis. Yet, PCPs described feeling uncomfortable with these conversations. Patients recommended that discussion of long-term prognosis be anchored to clinical decisions, that information be provided on how this information may be useful, and that patient interest in prognosis be assessed before prognostic information is offered. PCPs recommended that scripts be brief. These recommendations were used to develop example scripts to guide these conversations. CONCLUSIONS: We developed scripts and strategies for PCPs to introduce the topic of long-term prognosis with older adults and to provide numerical prognostic information to those interested. Future studies will need to test the effect of these strategies in practice.

Primary Care Providers' Perceptions of the Acceptability, Appropriateness, and Feasibility of a Mammography Decision Aid for Women Aged 75 and Older.

Background. Clinicians need to find decision aids (DAs) useful for their successful implementation. Therefore, we aimed to conduct an exploratory study to learn primary care clinicians' (PCPs) perspectives on a mammography DA for women ≥75 to inform its implementation. Methods. We sent a cross-sectional survey to 135 PCPs whose patients had participated in a randomized trial of the DA. These PCPs practiced at 1 of 11 practices in Massachusetts or North Carolina. PCPs were asked closed-ended and open-ended questions on shared decision making (SDM) around mammography with women ≥75 and on the DA's acceptability, appropriateness, and feasibility. Results. Eighty PCPs participated (24 [30%] from North Carolina). Most (n = 69, 86%) thought that SDM about mammography with women ≥75 was extremely/very important and that they engaged women ≥75 in SDM around mammography frequently/always (n = 49, 61%). Regarding DA acceptability, 60% felt the DA was too long. Regarding appropriateness, 70 (89%) thought it was somewhat/very helpful and that it would help patients make more informed decisions; 55 (70%) would recommend it. Few (n = 6, 8%) felt they had other resources to support this decision. Regarding feasibility, 53 (n = 67%) thought it would be most feasible for patients to receive the DA before a visit from medical assistants rather than during or after a visit or from health educators. Most (n = 62, 78%) wanted some training to use the DA. Limitations. Sixty-nine percent of PCPs in this small study practiced in academic settings. Conclusions. Although PCPs were concerned about the DA's length, most found it helpful and informative and felt it would be feasible for medical assistants to deliver the DA before a visit. Implications. Study findings may inform implementation of this and other DAs.

Variation in Breast Cancer Risk Model Estimates Among Women in Their 40s Seen in Primary Care.

Background: The Gail, Breast Cancer Surveillance Consortium (BCSC), and Tyrer-Cuzick breast cancer risk prediction models are recommended for use in primary care. Calculating breast cancer risk is particularly important for women in their 40s when deciding on mammography, with some guidelines recommending screening for those with 5-year risk similar to women age 50 (≥1.1%). Yet, little is known about risk estimate agreement among models for these women. Materials and Methods: Four hundred nine Boston-area women 40-49 years of age completed a risk questionnaire before a primary care visit to compute their breast cancer risk. The kappa statistic was used to examine when (1) Gail and BCSC agreed on 5-year risk ≥1.1%; (2) Gail estimated 5-year risk ≥1.7% and Tyrer-Cuzick estimated 10-year risk ≥5% (guideline thresholds for recommending prevention medications); and when (3) Gail and Tyrer-Cuzick agreed on lifetime risk ≥20% (threshold for breast MRI using Tyrer-Cuzick). Results: Participant mean age was 44.1 years, 56.7% were non-Hispanic white, and 7.8% had a first-degree relative with breast cancer. Of 266 with breast density information to estimate both Gail and BCSC, the models agreed on 5-year risk being ≥1.1% for 36 women, kappa = 0.34 (95% confidence interval: 0.23-0.45). Gail and Tyrer-Cuzick estimates led to agreement about prevention medications for 8 women, kappa 0.41 (0.20-0.61), and models agreed on lifetime risk ≥20% for 3 women, kappa 0.08 (-0.01 to 0.16). Conclusions: There is weak agreement on breast cancer risk estimates generated by risk models recommended for primary care. Using different models may lead to different clinical recommendations for women in their 40s.

Older adults' perspectives on primary care telemedicine during the COVID-19 pandemic.

BACKGROUND: Prior to the COVID-19 pandemic there were many barriers to telemedicine primary care for adults ≥65 years including insurance coverage restrictions and having lower digital access and literacy. With the pandemic, insurance coverage broadened and many older adults utilized telemedicine creating an opportunity to learn from their experiences to inform future policy. METHODS: Between April 2020 and June 2021, we conducted a cross-sectional multimethod study of English-speaking, cognitively-intact, adults ≥65, who had a phone-only and/or video telemedicine visit with their primary care physician within one large Massachusetts health system (10 different practices) since March 2020. The study questionnaire asked participants their overall satisfaction with telemedicine (7-point scale) and to compare telemedicine with in-person care. We used linear regression to examine the association between participants' demographics, Charlson comorbidity score, and survey completion date with their satisfaction score. The questionnaire also included open-ended questions on perceptions of telemedicine; which were analyzed using qualitative methods. RESULTS: Of 278 eligible patients reached, 208 completed the questionnaire; mean age was 74.4 years (±4.4), 61.5% were female, 91.4% were non-Hispanic White, 64.4% had ≥1 comorbidity, and 47.2% had a phone-only visit. Regardless of their age, participants reported being satisfied with telemedicine; median score was 6.0 on the 7-point scale (25th percentile = 5.0 and 75th percentile = 7.0). Non-Whites satisfaction scores were on average 1 point lower than those of non-Hispanic Whites (p = 0.02). Those with comorbidity reported scores that on average were 0.5 points lower than those without comorbidity (p = 0.07). Overall, 39.5% felt their telemedicine visit was worse than in-person care; 4.9% thought it was better. Participants appreciated telemedicine's convenience but described frustrating technical challenges. While participants preferred in-person care, most wanted telemedicine to remain available. CONCLUSIONS: Adults ≥65 reported being satisfied with primary care telemedicine during the pandemic's first 14 months and wanted telemedicine to remain available.

Lighter sleep is associated with higher enlarged perivascular spaces burden in middle-aged and elderly individuals.

BACKGROUND: While healthy sleep is suggested to promote glymphatic clearance in the brain, poorer sleep may be associated with higher enlarged perivascular spaces (ePVS) burden, potentially representing impaired perivascular drainage. This study aims to evaluate the association between ePVS burden and polysomnographic sleep characteristics in a large community-based sample. METHODS: 552 dementia and stroke-free Framingham Heart Study participants (age: 58.6 ± 8.9 years; 50.4% men) underwent a full-night in-home polysomnography. Three years later on average, participants underwent a brain MRI. ePVS were rated in the basal ganglia and centrum semiovale, and dichotomized as low burden (<20 counts, grades 1 and 2) or high burden (>20 counts, grades 3 and 4). Logistic regression analyses relating sleep variables to subsequent ePVS burden were used, adjusted for age, sex, time interval between polysomnography and MRI, ApoE ε4 allele carrier status, hypertension, and smoking. RESULTS: Longer N1 sleep and shorter N3 sleep duration were associated with higher ePVS burden in the centrum semiovale. When stratifying these associations by subpopulations, longer N1 sleep duration with ePVS burden was observed especially in older individuals and hypertensive participants. Associations between ePVS burden and other sleep characteristics such as total sleep time and REM sleep duration varied according to ApoE ε4 allele carrier status. CONCLUSIONS: Lighter sleep, as characterized by longer N1 sleep and shorter slow-wave sleep, is associated with higher ePVS burden. These findings suggest that sleep architecture may be involved in glymphatic clearance and cerebral small vessel disease, which could be an important biological link between sleep and dementia risk.