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Dementia with Lewy bodies (DLB) is one of the most common degenerative dementias, but research on end-of-life experiences for people with DLB and their caregivers is limited. Dyads of individuals with moderate-advanced DLB and their primary informal caregivers were recruited from specialty clinics, advocacy organizations, and research registries and followed prospectively every 6 months. The current study examines results of caregiver study visits 3 months after the death of the person with DLB. These visits included the Last Month of Life survey, study-specific questions, and a semi-structured interview querying end-of-life experiences. Individuals with DLB (n = 50) died 3.24 ± 1.81 years after diagnosis, typically of disease-related complications. Only 44% of caregivers reported a helpful conversation with clinicians regarding what to expect at the end of life in DLB. Symptoms commonly worsening prior to death included: cognition and motor function, ADL dependence, behavioral features, daytime sleepiness, communication, appetite, and weight loss. Almost 90% of participants received hospice care, but 20% used hospice for <1 week. Most caregivers reported overall positive experiences in the last month of life, but this was not universal. Having information about DLB and what to expect, access to support, and hospice care were healthcare factors associated with positive and negative end of life experiences. Hospice experiences were driven by communication, care coordination, quality care, and caregiver education. Most caregivers of individuals who died with DLB reported positive end-of-life experiences. However, the study identified multiple opportunities for improvement relating to clinician counseling of patients/families, support/hospice referrals, and monitoring individuals with DLB to identify approaching end of life. Future research should quantitatively identify changes that herald end of life in DLB and develop tools that can assist clinicians in evaluating disease stage to better inform counseling and timely hospice referrals. Trial registration information: NCT04829656.

Rey's Auditory Verbal Learning Test (AVLT) is a widely used word list memory test. We update normative data to include adjustment for verbal memory performance differences between men and women and illustrate the effect of this sex adjustment and the importance of excluding participants with mild cognitive impairment (MCI) from normative samples. This study advances the Mayo's Older Americans Normative Studies (MOANS) by using a new population-based sample through the Mayo Clinic Study of Aging, which randomly samples residents of Olmsted County, Minnesota, from age- and sex-stratified groups. Regression-based normative T-score formulas were derived from 4428 cognitively unimpaired adults aged 30-91 years. Fully adjusted T-scores correct for age, sex, and education. We also derived T-scores that correct for (1) age or (2) age and sex. Test-retest reliability data are provided. From raw score analyses, sex explained a significant amount of variance in performance above and beyond age (8-10%). Applying original age-adjusted MOANS norms to the current sample resulted in significantly fewer-than-expected participants with low delayed recall performance, particularly in women. After application of new T-scores adjusted only for age, even in normative data derived from this sample, these age-adjusted T-scores showed scores <40 T occurred more frequently among men and less frequently among women relative to T-scores that also adjusted for sex. Our findings highlight the importance of using normative data that adjust for sex with measures of verbal memory and provide new normative data that allow for this adjustment for the AVLT.

INTRODUCTION Premenopausal bilateral oophorectomy (PBO) before the age of 46 years is associated with an increased risk of dementia. We investigated the long‐term effects of PBO performed before age 50 years on amyloid beta (Aβ), tau, and neurodegeneration imaging biomarkers of Alzheimer's disease (AD). METHODS Mayo Clinic Cohort Study of Oophorectomy and Aging‐2 participants were divided into early PBO (< 46 years; n = 61), and late PBO (46–49 years; n = 51) groups and were compared to referent women who did not undergo PBO (n = 119). RESULTS Early PBO was associated with thinner entorhinal cortex (p = 0.014), higher tau load at higher levels of Aβ load (Pp = 0.005), higher Aβ load (p = 0.026), and smaller temporal lobe cortical thickness (p = 0.022), only at older ages compared to the referent group. DISCUSSION PBO before the age of 46 years is associated with entorhinal cortex thinning, elevated tau at higher Aβ levels, along with an AD‐like pattern of atrophy at older ages. CLINICAL TRIALS REGISTRATION NCT03821857 sex‐specific effects of endocrine disruption on aging and AD. Highlights Premenopausal bilateral oophorectomy (PBO) before the ages of 46 (early PBO) years and ages 46 to 49 (late PBO) years was studied. Early PBO was associated with reduced entorhinal cortex thickness later in life. Early PBO was associated with greater amyloid beta (Aβ) load at older ages. Early PBO was associated with greater Alzheimer's disease pattern of atrophy at older ages. Early PBO was associated with higher tau load at higher Aβ levels.

INTRODUCTION Few studies have comprehensively examined the impact of reproductive factors (i.e., reproductive window, parity, hormonal contraception [HC], and menopausal hormone therapy [MHT]) on global and domain‐specific cognition in later life. METHODS We studied a population‐based sample of 2458 women (median age 74.2 years) residing in Olmsted County, Minnesota; participants underwent a clinical evaluation and comprehensive cognitive testing. RESULTS The length of a woman's reproductive window was not associated with cognition. Higher parity was associated with greater cognitive decline in all domains. Ever HC use was associated with less decline in all domains. Ever MHT use was associated with greater decline in global cognition and all domain‐specific z‐scores except visuospatial; results were driven by women who initiated MHT 5 or more years after menopause. Additional adjustments for APOE and vascular‐related covariates did not attenuate the results. DISCUSSION Multiple reproductive risk factors are associated with cognitive decline in later life. Highlights The length of a woman's reproductive window was not associated with cognition longitudinally. Greater parity was associated with greater cognitive decline longitudinally. Ever HC use was associated with less decline in global cognition and all domain‐specific z‐scores longitudinally (all p < 0.01). Ever MHT use was associated with greater decline in global cognition and all domain‐specific z‐scores except visuospatial longitudinally (all p < 0.01). The greatest cognitive decline was among women who initiated MHT more than 5 years after menopause.

Normative neuropsychological data are essential for interpretation of test performance in the context of demographic factors. The Mayo Normative Studies (MNS) aim to provide updated normative data for neuropsychological measures administered in the Mayo Clinic Study of Aging (MCSA), a population-based study of aging that randomly samples residents of Olmsted County, Minnesota, from age- and sex-stratified groups. We examined demographic effects on neuropsychological measures and validated the regression-based norms in comparison to existing normative data developed in a similar sample. The MNS includes cognitively unimpaired adults ≥30 years of age ( = 4,428) participating in the MCSA. Multivariable linear regressions were used to determine demographic effects on test performance. Regression-based normative formulas were developed by first converting raw scores to normalized scaled scores and then regressing on age, age , sex, and education. Total and sex-stratified base rates of low scores ( < 40) were examined in an older adult validation sample and compared with Mayo's Older Americans Normative Studies (MOANS) norms. Independent linear regressions revealed variable patterns of linear and/or quadratic effects of age ( = 6-27% variance explained), sex (0-13%), and education (2-10%) across measures. MNS norms improved base rates of low performance in the older adult validation sample overall and in sex-specific patterns relative to MOANS. Our results demonstrate the need for updated norms that consider complex demographic associations on test performance and that specifically exclude participants with mild cognitive impairment from the normative sample.

The associations of bilateral oophorectomy among premenopausal women, age at oophorectomy, and use of estrogen therapy after oophorectomy with cognitive performance later in life remain controversial. To investigate whether women who underwent premenopausal bilateral oophorectomy were at increased risk of mild cognitive impairment (MCI) and experienced decreased global or domain-specific cognitive performance. This case-control study and cross-sectional study were made possible by combining data from the Mayo Clinic Study of Aging (MCSA) and the Rochester Epidemiology Project (REP) medical record-linkage system. The studies were conducted among a population-based sample in Olmsted County, Minnesota, consisting of 2732 women aged 50 to 89 years who participated in the MCSA study from 2004 to 2019 and underwent a clinical evaluation and comprehensive cognitive testing. Data were analyzed from January to May 2021. Medical record documentation of bilateral oophorectomy abstracted from a medical record-linkage system (ie, REP). Odds of MCI and global or domain-specific z scores on cognitive tests were measured at the first MCSA visit. The median (IQR) lag time between bilateral oophorectomy performed before menopause and before age 50 years and cognitive evaluation was 30 (22-38) years. Among 2732 women aged 50 to 89 years (median [IQR] age at evaluation, 74 [66-81] years) who participated in the MCSA, the case-control study included 283 women with MCI (10.4%) and 2449 women without cognitive impairment (89.6%). Bilateral oophorectomy before menopause and before age 46 years was associated with clinically diagnosed MCI (adjusted odds ratio [aOR], 2.21; 95% CI, 1.41-3.45; P < .001) compared with no bilateral oophorectomy. The presence of an association with MCI varied by surgical indication, with an association among 259 women with bilateral oophorectomy before menopause and before age 50 years for the indication of benign ovarian condition (aOR, 2.43; 95% CI, 1.36-4.33; P = .003) but not for cancer or no ovarian condition. The presence of an association did not vary by estrogen therapy after bilateral oophorectomy, with associations among women aged less than 46 years with estrogen therapy (aOR, 2.56; 95% CI, 1.24-5.31; P = .01) and without estrogen therapy (aOR, 2.05; 95% CI, 1.18-3.52; P = .01). The cross-sectional study included 625 women with a history of bilateral oophorectomy (median [IQR] age, 75 [70-82] years) and 2107 women without a history of bilateral oophorectomy (median [IQR] age, 73 [65-80] years). Premenopausal bilateral oophorectomy was performed before age 46 years among 161 women and was associated with decreased global cognition z score (β, -0.17; 95% CI, -0.32 to -0.03; P = .02), attention and executive domain z score (β, -0.21; 95% CI, -0.36 to -0.05; P = .009), and Short Test of Mental Status score (β, -0.51; 95% CI, -0.95 to -0.08; P = .02) compared with no bilateral oophorectomy. This study found that women who underwent bilateral oophorectomy before menopause had increased odds of MCI and poorer performance on cognitive tests approximately 30 years later compared with women who did not undergo bilateral oophorectomy.

INTRODUCTION Patients with dementia with Lewy bodies (DLB) may have Alzheimers disease (AD) pathology that can be detected by plasma biomarkers. Our objective was to evaluate plasma biomarkers of AD and their association with positron emission tomography (PET) biomarkers of amyloid and tau deposition in the continuum of DLB, starting from prodromal stages of the disease. METHODS The cohort included patients with isolated rapid eye movement (REM) sleep behavior disorder (iRBD), mild cognitive impairment with Lewy bodies (MCI‐LB), or DLB, with a concurrent blood draw and PET scans. RESULTS Abnormal levels of plasma glial fibrillary acidic protein (GFAP) were found at the prodromal stage of MCI‐LB in association with increased amyloid PET. Abnormal levels of plasma phosphorylated tau (p‐tau)‐181 and neurofilament light (NfL) were found at the DLB stage. Plasma p‐tau‐181 showed the highest accuracy in detecting abnormal amyloid and tau PET in patients with DLB. DISCUSSION The range of AD co‐pathology can be detected with plasma biomarkers in the DLB continuum, particularly with plasma p‐tau‐181 and GFAP.

To compare the Short Test of Mental Status (STMS) with the Montreal Cognitive Assessment (MoCA) for predicting and detecting mild cognitive impairment (MCI). Participants from the community-based Mayo Clinic Study of Aging (MCSA) (November 24, 2010, through May 19, 2012) and an academic referral Alzheimer’s Disease Research Center (ADRC) (March 16, 2015, through September 5, 2018) were analyzed. All participants were evaluated using a standardized neuropsychological battery, and a multidisciplinary consensus diagnosis was assigned. The MCSA and ADRC samples included 313 and 106 stable cognitively normal (CN) participants, 72 and 8 CN participants at baseline who developed incident MCI or dementia, 114 and 96 participants with prevalent MCI, and 25 and 132 participants with dementia, respectively. There were no statistically significant differences between the 2 tests in 6 of 7 diagnostic comparisons across academic referral and community populations. The STMS had a better area under the curve (0.90; 95% CI, 0.87-0.93) for differentiating prevalent MCI from CN participants in the MCSA cohort compared with the MoCA cohort (0.85; 95% CI, 0.81-0.89; P=.01). In addition, 53% of the stable CN participants (222 of 419) scored less than 26 on the MoCA, with specificity of 47% for diagnosing prevalent MCI. We provide evidence that the STMS performs similarly to the MoCA in a variety of settings and neurodegenerative syndromes. These results suggest that the current recommended MoCA cutoff score may be overly sensitive, consistent with previous studies. We also provide a conversion table for comparing the 2 cognitive tests.

INTRODUCTION We aimed to compare gait between individuals with Alzheimer's disease (AD), dementia with Lewy bodies (DLB), and cognitively unimpaired (CU) individuals and to evaluate the association between gait and regional amyloid beta (Aβ) burden in AD and DLB. METHODS We included 420 participants (70 AD, 70 DLB, 280 CU) in the Mayo Clinic Study of Aging (MCSA). Gait was assessed using a pressure‐sensor walkway. Aβ deposition was analyzed with Pittsburgh compound B (PiB) positron emission topography (PET). RESULTS The DLB group had reduced stride velocity, step length, and stride width variability, as well as increased double support percentage (%DS) and variability in step length, swing time, and step time compared to the AD and CU groups. Aβ burden was not associated with any gait outcomes. DISCUSSION This study provides additional evidence that gait differs between AD and DLB. Larger studies are needed to investigate associations between Aβ burden and gait outcomes in dementia. Highlights Gait was more impaired in dementia than in cognitively unimpaired (CU) controls. Compared with Alzheimer's disease (AD), Dementia with Lewy bodies (DLB) had more impaired pace, variability, and postural control. Step length and double support (%) distinguished DLB and AD with moderate accuracy.

Arterial spin labeled (ASL) magnetic resonance imaging (MRI) is the primary method for noninvasively measuring regional brain perfusion in humans. We introduce ASLPrep, a suite of software pipelines that ensure the reproducible and generalizable processing of ASL MRI data. ASLPrep is a software suite for reproducible processing of arterial spin labeled magnetic resonance imaging data.