Association of neighborhood socioeconomic disadvantage and cognitive impairment.

INTRODUCTION: We investigated the association of the area deprivation index (ADI) with cognitive decline, mild cognitive impairment (MCI), and dementia in older adults (≥50 years old). ADI is a neighborhood socioeconomic disadvantage measure assessed at the census block group level. METHODS: The study included 4699 participants, initially without dementia, with available ADI values for 2015 and at least one study visit in 2008 through 2018. Using logistic regression and Cox proportional hazards models with age as the time scale, we assessed the odds for MCI and the risk for dementia, respectively. RESULTS: In cognitively unimpaired (CU) adults at baseline, the risk for progression to dementia increased for every decile increase in the ADI state ranking (hazard ratio = 1.06, 95% confidence interval (1.01-1.11), P = .01). Higher ADI values were associated with subtly faster cognitive decline. DISCUSSION: In older CU adults, higher baseline neighborhood socioeconomic deprivation levels were associated with progression to dementia and slightly faster cognitive decline. HIGHLIGHTS: The study used area deprivation index, a composite freely available neighborhood deprivation measure. Higher levels of neighborhood deprivation were associated with greater mild cognitive impairment odds. Higher neighborhood deprivation levels were associated with higher dementia risk.

Comparison of CSF phosphorylated tau 181 and 217 for cognitive decline.

INTRODUCTION: The prognostic utility of cerebrospinal fluid (CSF) phosphorylated tau 217 (p-tau217) and p-tau181 is not understood. METHODS: Analyses included 753 Mayo Clinic Study on Aging participants (median age = 71.6; 57% male). CSF amyloid beta (Aß)42 and p-tau181 were measured with Elecsys immunoassays. CSF p-tau181 and p-tau217 were also measured with Meso Scale Discovery (MSD). We used Cox proportional hazards models for risk of mild cognitive impairment (MCI) and linear mixed models for risk of global and domain-specific cognitive decline and cortical thickness. Analyses were stratified by elevated brain amyloid based on CSF Aß42 or amyloid positron emission tomography for those with imaging. RESULTS: CSF p-tau217 was superior to p-tau181 for the diagnosis of Alzheimer's disease (AD) pathology. CSF MSD p-tau181 and p-tau217 were associated with risk of MCI among amyloid-positive individuals. Differences between CSF p-tau measures predicting cortical thickness were subtle. DISCUSSION: There are subtle differences for CSF p-tau217 and p-tau181 as prognostic AD markers.

The temporal onset of the core features in dementia with Lewy bodies.

INTRODUCTION: We examined the temporal sequence of the core features in probable dementia with Lewy bodies (DLB). METHODS: In 488 patients with probable DLB, the onset of each core feature and time to diagnosis was determined for men and women, and a pathologic subgroup (n = 209). RESULTS: REM sleep behavior disorder (RBD) developed before the other core features in men and women. Men were more likely to have RBD and were diagnosed with probable DLB earlier than women. Visual hallucinations developed after the other core features in men, but in women, they appeared earlier and concurrently with fluctuations and parkinsonism. Women were older and more cognitively impaired at first visit, were less likely to have RBD, more likely to be diagnosed with probable DLB later than men, and more likely to have neocortical tangles. DISCUSSION: An earlier latency to probable DLB was associated with men, RBD, and Lewy body disease without neocortical tangles.

Population-Based Prevalence of Infarctions on 3D Fluid-Attenuated Inversion Recovery (FLAIR) Imaging.

OBJECTIVES: To report population-based, age-specific prevalence of infarctions as identified via 3D fluid-attenuated inversion recovery (FLAIR) imaging. MATERIALS AND METHODS: Participants without dementia in the Mayo Clinic Study of Aging (MCSA), a population-based study in Olmsted County, MN, age 50-89 who underwent 3D FLAIR imaging between 2017 and 2020 were included. Infarctions per participant were determined via visual interpretation. Inter- and intra-reader reliability were calculated. Infarction prevalence on 3D FLAIR was derived by standardization to the Olmsted County population and was compared to that previously reported on 2D FLAIR imaging. RESULTS: Among 580 participants (mean age 71 years, 46% female) the prevalence (95% confidence interval) of any infarction was 5.0% (0.0%-9.9%) at age 50-59 years and 38.8% (28.6%-49.0%) at 80-89 years. In addition to increasing with age, the prevalence varied by sex and type of infarction. Prevalence estimates of cortical infarcts were 0.9% (0.0%-2.7%) at age 50-59 years and 20.2% (10.7%-29.7%) at 80-89 years and lacunar infarcts 4.1% (0.0%-8.8%) at age 50-59 years and 31.2% (21.5%-41.0%) at 80-89 years. Prevalence estimates of any infarction by sex were: men, 8.7% (0.0%-18.7%) at 50-59 years and 54.9% (41.0%-68.8%) at 80-89 years and women, 2.4% (0.0%-7.3%) at age 50-59 years and 27.3% (12.9%-41.7%) at 80-89 years. Intra- and inter- reader reliability were very good (kappa = 0.85 and 0.82, respectively). After adjusting for age, sex and education, individuals imaged with 3D FLAIR were 1.5 times (95% CI 1.2-1.8, p<0.001) more likely to be identified as positive for infarction compared to those imaged with 2D FLAIR. CONCLUSIONS: Infarction prevalence increases with age and is greater in men than women. Infarction prevalence on 3D FLAIR imaging, which has become more widely implemented as an alternative to 2D FLAIR over the past several years, will be a useful reference in future work.

Androgen Deprivation Therapy Use and Risk of Mild Cognitive Impairment in Prostate Cancer Patients.

INTRODUCTION: We examined the association between androgen deprivation therapy (ADT) use and the risk of mild cognitive impairment (MCI) among prostate cancer patients. METHODS: We included 241 cognitively unimpaired men, aged 70 to 90, with a history of prostate cancer before enrollment in the population-based Mayo Clinic Study of Aging. Using the Rochester Epidemiology Project medical records-linkage system, ADT use and length of exposure were abstracted. Follow-up visits occurred every 15 months and MCI diagnoses were made based on clinical consensus. Cox proportional hazards models, with age as the timescale, were used to examine the association between ADT use (yes/no) and length of exposure with the risk of MCI adjusting for education, apolipoprotein E, depression, and the Charlson Index score. RESULTS: There was no association between any ADT use (27.8% of participants) and the risk of MCI in the multivariable model [hazard ratio (HR), 1.25; 95% confidence interval (CI), 0.75-2.10]. Although not significant, there was an ADT dose-response relationship for risk of MCI: <5 years versus no use (HR, 1.08; 95% CI, 0.60-1.96) and ≥5 years versus not use (HR, 1.89; 95% CI, 0.83-4.27). CONCLUSION: ADT use among prostate cancer patients was not associated with an increased risk of developing MCI.

Informant-based hearing difficulties and the risk for mild cognitive impairment and dementia.

BACKGROUND: hearing loss has been associated with mild cognitive impairment (MCI) and dementia. Studies have not assessed whether hearing difficulties (HD) that interfere with daily activities as reported by partners can be a marker for increased risk for cognitive decline and impairment. OBJECTIVE: to assess the cross-sectional and longitudinal associations between informant-based HD, which interfere with daily activities and the risk for MCI and dementia. METHODS: the study included 4812 participants without dementia, enrolled in the Mayo Clinic Study of Aging (mean age (SD) 73.7 (9.6) years) with cognitive evaluation and informant-based report on participant's HD that interfere significantly with daily activities at baseline and for every 15 months. Cox proportional hazards models (utilising time-dependent HD status and age as the time scale) were used to examine HD and the risk for MCI or dementia, and mixed-effects models (allowing for random subject-specific intercepts and slopes) were used to examine the relationship between HD and cognitive decline. RESULTS: about, 981 participants had HD and 612 (12.7%) had prevalent MCI at baseline; 759 participants developed incident MCI and 273 developed incident dementia. In cognitively unimpaired participants at baseline, those with HD had higher risk for MCI (hazard ratio [HR] = 1.29, 95% confidence interval [CI] (1.10, 1.51), P = 0.002; adjusting for sex, years of education). In participants without dementia, those with HD had higher risk for dementia (HR: 1.39, 95% CI, (1.08-1.79), P = 0.011; adjusting sex and education). In individuals with MCI, HD was associated with modestly greater cognitive decline. CONCLUSIONS: informant-based HD was associated with increased risk for MCI and dementia.

Incidence of Convexal Subarachnoid Hemorrhage in the Elderly: The Mayo Clinic Study of Aging.

OBJECTIVES: Nontraumatic convexal subarachnoid hemorrhages in the elderly can be a manifestation of cerebral amyloid angiopathy associated with a high risk of future intracerebral hemorrhage. The incidence in the elderly population is unknown. Our objectives were to: 1) determine the incidence of convexal subarachnoid hemorrhage in a population-based study, and, 2) to compare apopolipoprotein-E genotype and amyloid positron emission tomographic (PET) imaging for those with versus without hemorrhage. METHODS: Between 11/29/2004 and 3/11/2017, 4462 individuals without hemorrhage at baseline participated in the population-based Mayo Clinic Study of Aging. We used the Rochester Epidemiology Project medical records-linkage system to identify intracerebral hemorrhages. Records and images were reviewed to identify convexal subarachnoid hemorrhage. Neuroimaging characteristics, demographics, medications, and apopolipoprotein-E genotype were recorded. RESULTS: Four cases were identified. The incidence of convexal subarachnoid hemorrhage was 14.1 per 100,000 person years. Three occurred in women, median age, 79 (range: 71-84). One patient had coexisting cerebral microbleeds. Two participants developed a subsequent lobar intracerebral hemorrhage at a median of 4.75 years after convexal subarachnoid hemorrhage. The apopolipoprotein-E -allele combinations of the 4 were: 3/3, 3/3, 2/2, and 2/3. On Pittsburgh Compound B-PET imaging, median standardized uptake value ratio with convexal subarachnoid hemorrhage was 1.86 (range: 1.38-2.34). CONCLUSIONS: Convexal subarachnoid hemorrhage is rare in the older population, occurring with an incidence of about 14 per 100,000 person years. Yet, when present, it may be associated with a high risk of future intracerebral hemorrhage.

Efficacy, Safety, and Tolerability of Armodafinil Therapy for Hypersomnia Associated with Dementia with Lewy Bodies: A Pilot Study.

BACKGROUND/AIMS: Hypersomnia is common in dementia with Lewy bodies (DLB). We assessed the efficacy, safety, and tolerability of armodafinil for hypersomnia associated with DLB. METHODS: We performed a 12-week pilot trial of armodafinil therapy (125-250 mg orally daily) in DLB outpatients with hypersomnia. The patients underwent neurologic examinations, a neuropsychological battery, laboratory testing, electrocardiography, and polysomnography. Efficacy was assessed at 2, 4, 8, and 12 weeks. Safety assessment included laboratory examinations, QTc interval, and heart rate. Tolerability was assessed by analysis of adverse events. Data were analyzed using the last-observation-carried-forward method. RESULTS: Of 20 participants, 17 completed the protocol. The median age was 72 years, most of the participants were men (80%), and most had spouses as caregivers. The Epworth Sleepiness Scale (p < 0.001), Maintenance of Wakefulness Test (p = 0.003), and Clinical Global Impression of Change (p < 0.001) scores improved at week 12. The Neuropsychiatric Inventory total score (p = 0.003), visual hallucinations (p = 0.003), and agitation (p = 0.02) improved at week 4. Caregiver overall quality of life improved at week 12 (p = 0.004). No adverse events occurred. CONCLUSION: These pilot data suggest improvements in hypersomnia and wakefulness and reasonable safety and tolerability of armodafinil therapy in hypersomnolent patients with DLB. Our findings inform the use of pharmacologic strategies for managing hypersomnolence in these patients.

Mediterranean diet, micronutrients and macronutrients, and MRI measures of cortical thickness.

INTRODUCTION: The Mediterranean diet (MeDi) is associated with reduced risk of cognitive impairment, but it is unclear whether it is associated with better brain imaging biomarkers. METHODS: Among 672 cognitively normal participants (mean age, 79.8 years, 52.5% men), we investigated associations of MeDi score and MeDi components with magnetic resonance imaging measures of cortical thickness for the four lobes separately and averaged (average lobar). RESULTS: Higher MeDi score was associated with larger frontal, parietal, occipital, and average lobar cortical thickness. Higher legume and fish intakes were associated with larger cortical thickness: legumes with larger superior parietal, inferior parietal, precuneus, parietal, occipital, lingual, and fish with larger precuneus, superior parietal, posterior cingulate, parietal, and inferior parietal. Higher carbohydrate and sugar intakes were associated with lower entorhinal cortical thickness. DISCUSSION: In this sample of elderly persons, higher adherence to MeDi was associated with larger cortical thickness. These cross-sectional findings require validation in prospective studies.

Eligibility for Anti-Amyloid Treatment in a Population-Based Study of Cognitive Aging.

BACKGROUND AND OBJECTIVES: Treatment options for Alzheimer disease (AD) are limited and have focused mainly on symptomatic therapy and improving quality of life. Recently, lecanemab, an anti-ß-amyloid monoclonal antibody (mAb), received accelerated approval by the US Food and Drug Administration for treatment in the early stages of biomarker-confirmed symptomatic AD. An additional anti-ß-amyloid mAb, aducanumab, was approved in 2021, and more will potentially become available in the near future. Research on the applicability and generalizability of the anti-ß-amyloid mAb eligibility criteria on adults with biomarkers available in the general population has been lacking. The study's primary aim was to apply the clinical trial eligibility criteria for lecanemab treatment to participants with early AD of the population-based Mayo Clinic Study of Aging (MCSA) and assess the generalizability of anti-amyloid treatment. The secondary aim of this study was to apply the clinical trial eligibility criteria for aducanumab treatment in MCSA participants. METHODS: This cross-sectional study aimed to apply the clinical trial eligibility criteria for lecanemab and aducanumab treatment to participants with early AD of the population-based MCSA and assess the generalizability of anti-amyloid treatment. RESULTS: Two hundred thirty-seven MCSA participants (mean age [SD] 80.9 [6.3] years, 54.9% male, and 97.5% White) with mild cognitive impairment (MCI) or mild dementia and increased brain amyloid burden by PiB PET comprised the study sample. Lecanemab trial's inclusion criteria reduced the study sample to 112 (47.3% of 237) participants. The trial's exclusion criteria further narrowed the number of potentially eligible participants to 19 (overall 8% of 237). Modifying the eligibility criteria to include all participants with MCI (instead of applying additional cognitive criteria) resulted in 17.4% of participants with MCI being eligible for lecanemab treatment. One hundred four participants (43.9% of 237) fulfilled the aducanumab clinical trial's inclusion criteria. The aducanumab trial's exclusion criteria further reduced the number of available participants, narrowing those eligible to 12 (5.1% of 237). Common exclusions were related to other chronic conditions and neuroimaging findings. DISCUSSION: Findings estimate the limited eligibility in typical older adults with cognitive impairment for anti-ß-amyloid mAbs.

Association of Performance on the Financial Capacity Instrument-Short Form With Brain Amyloid Load and Cortical Thickness in Older Adults.

Background and Objectives: To investigate the association of the Financial Capacity Instrument-Short Form (FCI-SF) performance and timing total scores with brain ß-amyloid and cortical thickness in cognitively unimpaired (CU) (at baseline) older adults. Methods: A total of 309 participants (aged 70 years or older) of the Mayo Clinic Study of Aging underwent 11C-Pittsburgh compound B PET amyloid imaging and MRI, and completed the FCI-SF. Abnormal amyloid PET was defined as standardized uptake value ratio ≥1.48 in an Alzheimer disease (AD)-related region of interest and reduced AD signature cortical thickness as ≤2.68 mm (neurodegeneration). A cohort of 218 (of the 309) participants had follow-up visits (every 15 months) with FCI-SF data for longitudinal analysis (number of visits including baseline, median [range]: 2 [2-4]). In the analysis, we used linear regression and mixed-effects models adjusted for age, sex, education, apolipoprotein E ε4 allele status, global cognitive z score, and previous FCI-SF testing. Results: Participants' mean age (SD) was 80.2 (4.8) years (56.3% male individuals). In cross-sectional analysis, abnormal amyloid PET (vs normal) was associated with a lower FCI-SF total score and slower total composite time. In longitudinal analysis, FCI-SF total score declined faster (difference in annualized rate of change, beta coefficient [ß] [95% confidence interval (CI)] = -1.123 [-2.086 to -0.161]) and FCI-SF total composite time increased faster (difference in annualized rate of change, ß [95% CI] = 16.274 [5.951 to 26.597]) for participants with neurodegeneration at baseline (vs those without). Participants who exhibited both abnormal amyloid PET and neurodegeneration at baseline had a greater increase in total composite time when compared with the group without abnormal amyloid and without neurodegeneration (difference in annualized rate of change, ß [95% CI] = 16.750 [3.193 to 30.307]). Discussion: Performance and processing speed on the FCI-SF were associated with imaging biomarkers of AD pathophysiology in CU (at baseline) older adults. Higher burdens of imaging biomarkers were associated with longitudinal worsening on FCI-SF performance. Additional research is needed to delineate further these associations and their predictive utility at the individual person level.

Meta-analysis of 8q24 for seven cancers reveals a locus between NOV and ENPP2 associated with cancer development.

BACKGROUND: Human chromosomal region 8q24 contains several genes which could be functionally related to cancer, including the proto-oncogene c-MYC. However, the abundance of associations around 128 Mb on chromosome 8 could mask the appearance of a weaker, but important, association elsewhere on 8q24. METHODS: In this study, we completed a meta-analysis of results from nine genome-wide association studies for seven types of solid-tumor cancers (breast, prostate, pancreatic, lung, ovarian, colon, and glioma) to identify additional associations that were not apparent in any individual study. RESULTS: Fifteen SNPs in the 8q24 region had meta-analysis p-values < 1E-04. In particular, the region consisting of 120,576,000-120,627,000 bp contained 7 SNPs with p-values < 1.0E-4, including rs6993464 (p = 1.25E-07). This association lies in the region between two genes, NOV and ENPP2, which have been shown to play a role in tumor development and motility. An additional region consisting of 5 markers from 128,478,000 bp - 128,524,000 (around gene POU5F1B) had p-values < 1E-04, including rs6983267, which had the smallest p-value (p = 6.34E-08). This result replicates previous reports of association between rs6983267 and prostate and colon cancer. CONCLUSIONS: Further research in this area is warranted as these results demonstrate that the chromosomal region 8q24 may contain a locus that influences general cancer susceptibility between 120,576 and 120,630 kb.

Genetic variants and risk of lung cancer in never smokers: a genome-wide association study.

BACKGROUND: Lung cancer in individuals who have never smoked tobacco products is an increasing medical and public-health issue. We aimed to unravel the genetic basis of lung cancer in never smokers. METHODS: We did a four-stage investigation. First, a genome-wide association study of single nucleotide polymorphisms (SNPs) was done with 754 never smokers (377 matched case-control pairs at Mayo Clinic, Rochester, MN, USA). Second, the top candidate SNPs from the first study were validated in two independent studies among 735 (MD Anderson Cancer Center, Houston, TX, USA) and 253 (Harvard University, Boston, MA, USA) never smokers. Third, further replication of the top SNP was done in 530 never smokers (UCLA, Los Angeles, CA, USA). Fourth, expression quantitative trait loci (eQTL) and gene-expression differences were analysed to further elucidate the causal relation between the validated SNPs and the risk of lung cancer in never smokers. FINDINGS: 44 top candidate SNPs were identified that might alter the risk of lung cancer in never smokers. rs2352028 at chromosome 13q31.3 was subsequently replicated with an additive genetic model in the four independent studies, with a combined odds ratio of 1.46 (95% CI 1.26-1.70, p=5.94x10(-6)). A cis eQTL analysis showed there was a strong correlation between genotypes of the replicated SNPs and the transcription level of the gene GPC5 in normal lung tissues (p=1.96x10(-4)), with the high-risk allele linked with lower expression. Additionally, the transcription level of GPC5 in normal lung tissue was twice that detected in matched lung adenocarcinoma tissue (p=6.75x10(-11)). INTERPRETATION: Genetic variants at 13q31.3 alter the expression of GPC5, and are associated with susceptibility to lung cancer in never smokers. Downregulation of GPC5 might contribute to the development of lung cancer in never smokers. FUNDING: US National Institutes of Health; Mayo Foundation.

Association of plasma ceramides with prevalent and incident type 2 diabetes mellitus in middle and older aged adults.

AIMS: The role of ceramides in the pathogenesis of type 2 diabetes mellitus (T2DM) is incompletely characterized. Given that ceramides represent therapeutic targets to disrupt the euglycemia-T2DM transition, we aimed to characterize their association with prevalent and incident T2DM in a novel cohort. METHODS: We examined the cross-sectional and longitudinal association of baseline ceramides with prevalent and incident T2DM among 1423 adults (47% women; median (range) baseline age 72 (51-95) years) in the Mayo Clinic Study of Aging cohort. We examined the associations of ceramides with prevalent T2DM (adjusted odds ratio [95% confidence interval]) at baseline and incident T2DM (adjusted hazard ratio [95% confidence interval]) during median follow-up of 6.2 years, after adjusting for demographic and metabolic factors. RESULTS: Among 1423 adults, there were 222 prevalent and 37 incident cases of T2DM. In cross-sectional analyses, higher levels of ceramide C16:0 were associated with lower odds of prevalent T2DM (aOR 0.84 [0.71-0.99];P = 0.03) whereas C18:0 (aOR 1.27 [1.06-1.42];P = 0.01), C18:0/16:0 (aOR 1.41 [1.22-1.62]; P < 0.001) and C18:0/24:0 (aOR 1.22 [1.05-1.41]; P = 0.01) were associated with higher odds. In Cox hazard regression models, C18:0/16:0 (aHR 1.63 [1.26-2.10];P < 0.001) and C18:0 (aHR 1.53 [1.12-2.08];P = 0.01) were associated with increased risk of incident T2DM. CONCLUSIONS: In this prospective population-based cohort, ceramides were associated with prevalent T2DM (C16:0,C18:0, C18:0/C16:0 ratio, C18:0/C24:0 ratio) and incident T2DM (C18:0, C18:0/C16:0 ratio) and could suggest targets for the primary and secondary prevention of T2DM.

Sex Difference in the Relation Between Marital Status and Dementia Risk in Two Population-Based Cohorts.

BACKGROUND: The modifying effect of sex on the relation between marital status and dementia has yet to be determined. OBJECTIVE: To examine if sex modifies the association between marital status and incident dementia. METHODS: Population-based samples from the Mayo Clinic Study of Aging (MCSA, N = 3,471) and the Gothenburg H70 Birth Cohort Study (H70-study, N = 913) were used. A multiplicative interaction term was used to analyze the modifying effect of sex on the relation between marital status (married versus not married) and incident dementia using Cox regression models. Further, risk of dementia by marital status was also evaluated in models separated by sex. RESULTS: In the MCSA, there was an interaction between marital status and sex in relation to dementia (p = 0.015). In contrast, in the H70-study, no significant interaction was observed (p = 0.28). Nevertheless, in both studies, not married men had increased risk of dementia compared to married men in models adjusted for age, education, and number of children (H70-study: 1.99; 1.06-3.76, MCSA: 1.43; 1.08-1.89). Associations remained similar after additional adjustment for depression, BMI, hypertension, dyslipidemia, and diabetes mellitus (H70-study: 2.00; 1.05-3.82, MCSA: 1.32; 0.99-1.76). Further, no significant association was observed between marital status and dementia in women (H70-study: 1.24; 0.82-1.89, MCSA: 0.82; 0.64-1.04). CONCLUSION: Sex had a modifying effect on the association between marital status and incident dementia. In analyses separated by sex, not married men had an increased risk of dementia compared to married men, while no significant association was observed between marital status and risk of dementia in women.

Brain amyloid, cortical thickness, and changes in activities of daily living.

OBJECTIVE: To examine the association of baseline elevated brain amyloid and neurodegeneration with changes in activities of daily living in participants without dementia (ND; i.e., cognitively unimpaired and participants with mild cognitive impairment) at baseline in the population-based Mayo Clinic Study of Aging. METHODS: We included 1747 ND participants with 11 C-PiB PET and MR imaging in the study, with data on activities of daily living (as assessed by the Functional Activities Questionnaire (FAQ) and the Clinical Dementia Rating scale Sum of Boxes for functional domains (CDR-SOB (functional)), with a median (range) of 4.3 (0.0-12.7) years of follow-up. Abnormal (elevated; A+) 11 C-PiB-PET retention ratio was defined as standardized uptake value ratio ≥ 1.48, and abnormal (reduced) AD signature cortical thickness as ≤ 2.68 mm (neurodegeneration; N+). Associations were examined with mixed effects models, adjusting for age, sex, education, apolipoprotein E ε4 allele carrier status, and global cognitive z-score. RESULTS: Mean age (SD) was 71.4 years (10.1), 46.7% were females, 195 (11.2%) had A+N-, 442 (25.3%) had A-N+, and 339 (19.4%) had A+N+ biomarkers. The A+N+ group had the largest annualized change in the FAQ score from baseline (difference in annual change A+N+ vs. A-N-; ß (SE): 0.80 (0.07)); associations were substantially attenuated when a time-varying global cognitive composite was included in the model (A+N+ vs. A-N-; ß (SE): 0.31 (0.05)). CDR-SOB (functional) findings partly agreed with FAQ score findings. INTERPRETATION: The longitudinal increase in functional limitations is greater for individuals with abnormal neuroimaging biomarkers, especially for those with both elevated brain amyloid and neurodegeneration.

Subtypes of dementia with Lewy bodies are associated with α-synuclein and tau distribution.

OBJECTIVE: To determine whether Lewy body disease subgroups have different clinical profiles. METHODS: Participants had dementia, autopsy-confirmed transitional or diffuse Lewy body disease (TLBD or DLBD) (n = 244), or Alzheimer disease (AD) (n = 210), and were seen at least twice (mean follow-up 6.2 ± 3.8 years). TLBD and DLBD groups were partitioned based on the presence or absence of neocortical neurofibrillary tangles using Braak staging. Four Lewy body disease subgroups and AD were compared on clinical features, dementia trajectory, and onset latency of probable dementia with Lewy bodies (DLB) or a DLB syndrome defined as probable DLB or dementia with one core feature of parkinsonism or probable REM sleep behavior disorder. RESULTS: In TLBD and DLBD without neocortical tangles, diagnostic sensitivity was strong for probable DLB (87% TLBD, 96% DLBD) and the DLB syndrome (97% TLBD, 98% DLBD) with median latencies <1 year from cognitive onset, and worse baseline attention-visual processing but better memory-naming scores than AD. In DLBD with neocortical tangles, diagnostic sensitivity was 70% for probable DLB and 77% for the DLB syndrome with respective median latencies of 3.7 years and 2.7 years from cognitive onset, each associated with tangle distribution. This group had worse baseline attention-visual processing than AD, but comparable memory-naming impairment. TLBD with neocortical tangles had 48% diagnostic sensitivity for probable DLB and 52% for the DLB syndrome, with median latencies >6 years from cognitive onset, and were cognitively similar to AD. Dementia trajectory was slowest for TLBD without neocortical tangles, and fastest for DLBD with neocortical tangles. CONCLUSIONS: The phenotypic expression of DLB was associated with the distribution of α-synuclein and tau pathology.

Prevalence and Heterogeneity of Cerebrovascular Disease Imaging Lesions.

OBJECTIVE: To report population age-specific prevalence of core cerebrovascular disease lesions (infarctions, cerebral microbleeds, and white-matter hyperintensities detected with magnetic resonance imaging); estimate cut points for white-matter hyperintensity positivity; investigate sex differences in prevalence; and estimate prevalence of any core cerebrovascular disease features. PATIENTS AND METHODS: Participants in the population-based Mayo Clinic Study of Aging aged 50 to 89 years underwent fluid-attenuated inversion recovery and T2* gradient-recalled echo magnetic resonance imaging to assess cerebrovascular disease between October 10, 2011, and September 29, 2017. We characterized each participant as having infarct, normal versus abnormal white-matter hyperintensity, cerebral microbleed, or a combination of lesions. Prevalence of cerebrovascular disease biomarkers was derived through adjustment for nonparticipation and standardization to the population of Olmsted County, Minnesota. RESULTS: Among 1462 participants without dementia (median [range] age, 68 [50 to 89] y; men, 52.7%), core cerebrovascular disease features increased with age. Prevalence (95% CI) of cerebral microbleeds was 13.6% (11.6%-15.6%); infarcts, 11.7% (9.7%-13.8%); and abnormal white-matter hyperintensity, 10.7% (8.7%-12.6%). Infarcts and cerebral microbleeds were more common among men. In contrast, abnormal white-matter hyperintensity was more common among women ages 60 to 79 y and men, ages 80 y and older. Prevalence of any core cerebrovascular disease feature determined by presence of at least one cerebrovascular disease feature increased from 9.5% (ages 50 to 59 y) to 73.8% (ages 80 to 89 y). CONCLUSION: Whereas this study focused on participants without dementia, the high prevalence of cerebrovascular disease imaging lesions in elderly persons makes assignment of clinical relevance to cognition and other downstream manifestations more probabilistic than deterministic.

Factors Associated With Meningioma Detected in a Population-Based Sample.

OBJECTIVE: To determine the frequency of incidental meningioma and identify associated factors in a population-based sample of participants who systematically underwent brain imaging. PATIENTS AND METHODS: We searched the Mayo Clinic Study of Aging, a population-based sample of Olmsted County, Minnesota, residents who underwent longitudinal magnetic resonance imaging of the brain. Using a text search of radiologists' notes for 2402 individuals (median age, 75.0 years) who underwent imaging between August 10, 2005, and July 31, 2014, we identified 52 patients (2.2%) who had at least one meningioma. We estimated the association of selected risk factors with the presence of meningioma using odds ratios and 95% CIs from logistic regression models adjusted for age and sex. Based on these results, we moved the most significant variables forward to a multivariable model. RESULTS: Controlling for age and sex, significant associations with the presence of meningioma included higher body mass index (odds ratio [OR], 1.06; 95% CI, 1.01-1.12; P=.03), nonsteroidal anti-inflammatory drugs (OR, 2.11; 95% CI, 1.13-3.95; P=.02), aspirin (OR, 1.90; 95% CI, 1.05-3.46; P=.04), and blood pressure-lowering medication (OR, 2.06; 95% CI, 1.06-3.99; P=.03). Lower risk was associated with male sex (OR, 0.51; 95% CI, 0.29-0.90; P=.02), coronary artery disease (OR, 0.46; 95% CI, 0.22-0.97; P=.04), and higher self-reported anxiety (OR, 0.88; 95% CI, 0.78-0.98; P=.02). Simultaneous adjustment for all of these factors except aspirin in a multivariable model did not attenuate these associations (concordance, 0.71). CONCLUSION: In a population-based sample of 2402 participants, 52 (2.2%) had an incidental meningioma. They were more likely to be female and have higher body mass index. Meningioma was also associated with certain medications (nonsteroidal anti-inflammatory drugs and blood pressure-lowering medications) and inversely with anxiety and coronary artery disease.

Comparison of the Short Test of Mental Status and the Montreal Cognitive Assessment Across the Cognitive Spectrum.

OBJECTIVE: To compare the Short Test of Mental Status (STMS) with the Montreal Cognitive Assessment (MoCA) for predicting and detecting mild cognitive impairment (MCI). PARTICIPANTS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.