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1.
Artigo em Inglês | MEDLINE | ID: mdl-31272924

RESUMO

INTRODUCTION: Mobility metrics derived from wearable sensor recordings are associated with parkinsonism in older adults. We examined if these metrics predict incident parkinsonism. METHODS: Parkinsonism was assessed annually in 683 ambulatory, community-dwelling older adults without parkinsonism at baseline. Four parkinsonian signs were derived from a modified Unified Parkinson's Disease Rating Scale (UPDRS). Parkinsonism was based on the presence of 2 or more signs. Participants wore a sensor on their back while performing a 32 foot walk, standing posture, and Timed Up and Go (TUG) tasks. 12 mobility scores were extracted. Cox proportional hazards models with backward elimination were used to identify combinations of mobility scores independently associated with incident parkinsonism. RESULTS: During follow-up of 2.5 years (SD = 1.28), 139 individuals developed parkinsonism (20.4%). In separate models, 6 of 12 mobility scores were individually associated with incident parkinsonism, including: Speed and Regularity (from 32 ft walk), Sway (from standing posture), and 3 scores from TUG subtasks (Posterior sit to stand transition, Range stand to sit transition, and Yaw, a measure of turning efficiency). When all mobility scores were analyzed together in a single model, 2 TUG subtask scores, Range from stand to sit transition (HR, 1.42, 95%CI, 1.09, 1.82) and Yaw from turning (HR, 0.56, 95%CI, 0.42, 0.73) were independently associated with incident parkinsonism. These results were unchanged when controlling for chronic health covariates. CONCLUSION: Mobility metrics derived from a wearable sensor complement conventional gait testing and have potential to enhance risk stratification of older adults who may develop parkinsonism.

2.
J Alzheimers Dis ; 70(1): 153-161, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31177216

RESUMO

BACKGROUND: Individuals taking renin angiotensin system (RAS) acting antihypertensives exhibit slower cognitive decline and are less likely to progress from mild cognitive impairment (MCI) to Alzheimer's disease (AD), but the mechanism remains unclear. OBJECTIVE: We tested the hypothesis that individuals taking RAS acting antihypertensives exhibit less AD-related neuropathology and slower disease progression than individuals taking non-RAS acting antihypertensives. METHOD: Participants included 83 individuals with MCI who were taking an antihypertensive at baseline, had at least two follow-up visits, and had postmortem neuropathological data. Participants were old (M = 83.1 years), 32% male, well educated (M = 15.7 years), and 9.2% Black. RESULTS: RAS medication users (N = 38) were less likely to progress to AD than non-RAS users (N = 45). RAS users exhibited fewer neurofibrillary tangles than non-RAS users in the hippocampal CA1 region (p < 0.01), entorhinal cortex (p = 0.03), and the angular gyrus, inferior temporal, mid-frontal cortex, and superior frontal (p = 0.01). CONCLUSION: Prevention or clearance of neurofibrillary tangles represents a mechanism by which RAS medications may slow disease progression.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31246244

RESUMO

BACKGROUND: Gait speed is a robust non-specific predictor of health outcomes. We examined if combinations of gait speed and other mobility metrics are associated with specific health outcomes. METHODS: A sensor (triaxial accelerometer and gyroscope) placed on the lower-back, measured mobility in the homes of 1249 older adults (77% female; 80.0, SD=7.72 years). Twelve gait scores were extracted from 5 performances including: a) walking, b) transition from sit to stand, c) transition from stand to sit, d) turning, and e) standing posture. Using separate Cox proportional hazards models, we examined which metrics were associated with time to mortality, incident ADL disability (ADL), mobility disability mild cognitive impairment (MCI) and Alzheimer's disease (AD) dementia. We employed a single integrated analytic framework to determine which gait scores survived to predict each outcome. RESULTS: During 3.6 years of follow-up, 10 of the 12 gait scores predicted one or more of the five health outcomes. In further analyses, different combinations of 2-3 gait scores survived backward elimination and were associated with the five outcomes. Sway was one of three scores which predicted ADL disability, but was not included in the final models for other outcomes. Gait speed was included along with other metrics in the final models predicting mortality and ADL disability but not for other outcomes. CONCLUSIONS: When analyzing multiple mobility metrics together, different combinations of mobility metrics are related to specific adverse health outcomes. Digital technology enhances our understanding of impaired mobility and may provide mobility biomarkers that predict distinct health outcomes.

4.
Neuropsychology ; 2019 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-31204814

RESUMO

OBJECTIVE: Greater financial and health literacy are associated with better cognition; however, research suggests that some individuals exhibit differences, or discrepancies, in these abilities in old age. We investigated discrepancies between literacy and cognition and factors associated with such discrepancies in older adults without dementia. METHOD: Participants (N = 714; Mage = 81.4; education: M = 15.4; 75.4% female; 5.2% non-White) from the Rush Memory and Aging Project completed cognitive assessments and a financial and health literacy measure that yielded a total literacy score. Participants were characterized into three groups: (a) total literacy scores that are more than one standard deviation (1 SD) above cognition (L > C), (b) total literacy scores falling more than 1 SD below cognition (L < C), and (c) total literacy within 1 SD of cognition (L = C). Logistic regressions were employed to investigate associations between demographic and psychosocial variables and discrepancy group status. RESULTS: Of the 714 participants, 24% showed significant discrepancies. In fully adjusted models, in reference to the L = C group, male sex was associated with greater odds of being in the L > C group (odds ratio [OR] = 2.32, 95% CI [1.33, 4.03], p = .003) and lower odds of being in the L < C group (OR = 0.31, 95% CI [0.14, 0.66], p = .002), higher income was associated with lower odds of being in either discrepancy group (L < C OR = 0.87, 95% CI [0.79, 0.96], p = .004; L > C OR = 0.86, 95% CI [0.76, 0.96], p = .007), and higher trust was associated with lower odds of being in the L > C group (OR = 0.92, 95% CI [0.85, 0.99], p = .030). CONCLUSIONS: Findings support literacy and cognition as partially dissociable constructs and highlight important factors associated with discrepancies between literacy and cognition. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

5.
Brain Res ; 1719: 11-16, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31128096

RESUMO

Alzheimer's dementia is the leading cause of dementia in older adults and women are disproportionately burdened. It is increasingly recognized that dementia in older persons is related to the co-occurrence of mixed pathologies in the brain, but few studies have examined whether the frequency of common pathologies vary by sex. We examined the frequency of the most common mixed pathologies that underlie Alzheimer's dementia in aging, including Alzheimer's disease (AD) in combination with Lewy Bodies, cerebrovascular disease (CVD) pathology, or TDP-43/Hippocampal sclerosis, and determined whether the patterns differed for women and men in a combined cohort of over 1500 older community-dwelling adults. We found in separate models that women were significantly more likely to have AD and CVD pathology than men, and men were more likely to have "pure" Lewy Body disease, in models adjusted for age at death, education, race, and the APOE-e4 allele. Although AD with TDP-43/Hippocampal sclerosis pathology was greater in number in women than men, the difference was not significant after adjustments for age at death and other confounders. Together these findings suggest sex differences in mixed pathology, specifically AD with CVD in older adults from the community.

6.
Alzheimer Dis Assoc Disord ; 33(3): 254-259, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31058682

RESUMO

PURPOSE: Heightened Alzheimer disease (AD) risk among African Americans represents a racial disparity in aging. This study examines perceptions of AD risk factors among nondemented older African Americans. METHODS: Participants indicated how important nine factors were in increasing one's AD risk using a Likert-type scale with endpoints 1=not at all important to 4=extremely important. We examined perceptions of AD risk factors as a function of age, education, gender, and global cognition using separate logistic regression models. PATIENTS: Participants were from The Minority Aging Research Study (N=610) with a mean age of 74.5 years, a mean education of 14.9 years, and 24% were men. RESULTS: Of the AD risk factors, predictors were significantly related to genetics and God's Will. Younger participants (est.=-0.06, P=0.02) and those with more education (est.=0.14, P=0.02) were more likely to report genetics as extremely important. Participants with more education were less likely to indicate God's Will as extremely important (est.=-0.14, P<0.0005). CONCLUSIONS: Among older African Americans, age and education were important characteristics for the perception of AD risk factors. Findings can facilitate designing effective, culturally competent educational tools for meaningful engagement with older African Americans about AD.

7.
Artigo em Inglês | MEDLINE | ID: mdl-30882155

RESUMO

OBJECTIVE: Investigate associations of early-life residence and school segregation with cognitive change in the Minority Aging Research Study. METHODS: 498 Blacks (age~73.5;75%=female) without dementia at baseline self-reported State of birth, residence at age 12, and school segregation status. Census Bureau definitions of South and Northeast/Midwest were used to categorize early-life residence. We evaluated global cognition and 5 cognitive domains at baseline and annually for ~7.5 years. Linear mixed-effects models examined the associations of region of birth and residence at age 12 with baseline level and longitudinal change in cognition. Additional models examined school segregation experience. RESULTS: ~65% of Southern born participants still lived in the South at age 12. Southern birth was associated with lower baseline global cognition and all cognitive domains (p-values<0.02) compared to Northern birth, but not cognitive change. A similar profile was seen for Southern residence at age 12. Segregation experience significantly modified associations of residence at age 12 on levels of cognition. Participants residing in the South attending a legally desegregated school demonstrated lower baseline levels of cognition (global, semantic, and working memory) than their Northeast/Midwest counterparts attending a legally desegregated or segregated school as well as their Southern counterparts attending a legally segregated school. This profile for participants attending a desegregated school in the South held for processing speed and visuospatial ability in comparisons to Northeast/Midwest counterparts, particularly those attending a legally desegregated school. CONCLUSION: Baseline cognition was poorer in individuals born and residing in the South, particularly those attending desegregated schools at age 12.

8.
Neurology ; 92(16): e1821-e1830, 2019 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-30894446

RESUMO

OBJECTIVE: To examine whether indices of Parkinson disease (PD) pathology and other brain pathologies are associated with the progression of parkinsonism in older adults. METHODS: We used data from decedents who had undergone annual clinical testing prior to death and structured brain autopsy. Parkinsonism was based on assessment with a modified Unified Parkinson's Disease Rating Scale and a clinical diagnosis of PD was based on medical history. We used a series of mixed-effects models controlling for age and sex to investigate the association of PD pathology (nigral neuronal loss and Lewy bodies) and indices of 8 other brain pathologies with the progression of parkinsonism prior to death. RESULTS: During an average of 8.5 years' follow-up, more than half (771/1,430, 53.9%) developed parkinsonism proximate to death. On average, parkinsonism was progressive (estimate 0.130, SE 0.005, p < 0.001) in all older adults, but more rapid in adults with a clinical diagnosis of PD (n = 52; 3.6%) (estimate 0.066, SE 0.021, p < 0.001). Progression of parkinsonism was more rapid in adults with PD pathology (estimate 0.087, SE 0.013, p < 0.001). Alzheimer disease and several cerebrovascular pathologies were all independently associated with more rapid progression (all p values <0.05). The association between a higher person-specific weighted pathology score and more rapidly progressive parkinsonism did not differ between individuals with and without a clinical diagnosis of PD (estimate 0.003, SE 0.047, p = 0.957). CONCLUSION: The rate of progressive parkinsonism in older adults with and without a clinical diagnosis of PD is related to the burden of mixed brain pathologies.

10.
Gait Posture ; 67: 224-229, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30380506

RESUMO

BACKGROUND: When older adults turn to sit, about 80% of the subjects complete the turn before starting to sit i.e., a distinct-strategy, while in about 20%, part of the turning and sitting take place concurrently, i.e., an overlapping-strategy. A prolonged duration of the separation between tasks in the distinct-strategy (D-interval) and a prolonged duration of the overlap interval in overlapping-strategy (O-interval) are related to worse motor symptoms and poorer cognition. In the present study, we evaluated what strategy is employed by patients with Parkinson's disease (PD) when they transition from turning to sitting. METHODS: 96 participants with PD performed turn to sit as part of the Timed Up and Go test, both with and without medications, while wearing a body-fixed sensor. We quantified the turn-to-sit transition and determined which strategy (distinct or overlapping) was employed. We then stratified the cases and used regression models adjusted for age, gender, height, and weight to examine the associations of the D-interval or O-interval with parkinsonian features and cognition. RESULTS: Most patients (66%) employed the overlapping-strategy, both off and on anti-parkinsonian medications. Longer O-intervals were associated with longer duration of PD, more severe PD motor symptoms, a higher postural-instability-gait-disturbance (PIGD) score, and worse freezing of gait. Longer D-intervals were not associated with disease duration or PD motor symptoms. Neither the D- nor O-intervals were related to cognitive function. Individuals who employed the overlapping-strategy had more severe postural instability (i.e., higher PIGD scores), as compared to those who used the distinct-strategy. SIGNIFICANCE: In contrast to older adults without PD, most patients with PD utilize the overlapping strategy. Poorer postural and gait control are associated with the strategy choice and with the duration of concurrent performance of turning and sitting. Additional work is needed to further explicate the mechanisms underlying these strategies and their clinical implications.


Assuntos
Cognição/fisiologia , Transtornos Neurológicos da Marcha/fisiopatologia , Doença de Parkinson/fisiopatologia , Equilíbrio Postural/fisiologia , Dispositivos Eletrônicos Vestíveis/estatística & dados numéricos , Acelerometria/instrumentação , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Técnicas de Diagnóstico Neurológico/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Postura Sentada , Estudos de Tempo e Movimento
11.
J Am Geriatr Soc ; 67(4): 734-740, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30584655

RESUMO

OBJECTIVES: To examine the effects of age and race on the association of apolipoprotein E (APOE) genotypes with cognitive decline in a population sample. DESIGN: Longitudinal study of 18 years' duration. SETTING: Biracial urban US population sample. PARTICIPANTS: There were a total of 5807 participants, 60% African American (AA) and 40% European American (EA). MEASUREMENTS: A composite cognitive function based on individual tests of episodic memory, perceptual speed, and the Mini-Mental State Examination. RESULTS: The frequencies of APOE ε2/ε3 (14% vs 12%), ε2/ε4 (4% vs 2%), ε3/ε4 (29% vs 22%), and ε4/ε4 (4% vs 2%) genotypes were higher among AAs than EAs. After adjusting for demographic factors, the rate of decline in global cognition was twice as high among participants with the APOE ε4/ε4 genotype compared to participants with the APOE ε3/ε3 genotype (0.097 vs 0.048 SD units [SDUs] per year; P < .0001). This doubling was not different between AAs (0.091 vs 0.045 SDUs per year) and EAs (0.118 vs 0.059 SDUs per year) (Pinteraction = .63). The APOE ε3/ε4 genotype was associated with a higher rate of decline with age (Pinteraction = .021), while the APOE ε2/ε4 genotype (Pinteraction = .016) and the APOE ε2/ε3 genotype (Pinteraction = .043) were associated with a lower rate of decline with higher age. The APOE ε2/ε2 genotype was associated with a lower rate of decline in episodic memory, while the APOE ε2/ε4 was associated with a higher rate of decline in episodic memory and perceptual speed. CONCLUSIONS: The association of the APOE genotypes with cognitive decline was not different between AAs and EAs. However, individuals with different APOE genotypes showed a lower or a higher rate of decline with age. J Am Geriatr Soc 67:734-740, 2019.

12.
Alzheimers Dement ; 2018 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-30321502

RESUMO

INTRODUCTION: Apolipoprotein E (APOE) is a susceptibility gene for late-onset Alzheimer's disease neuropathology; less is known about the relationship between APOE and cerebrovascular disease (CVD) neuropathology. METHODS: We investigated associations of APOE status with arteriolosclerosis, macroinfarcts and microinfarcts, and atherosclerosis in 1383 adults (65.9-108.2 years at death) with and without dementia. Excluding ε2/ε4 carriers, multivariable regressions for each CVD-related neuropathology compared ε4 and ε2 carriers to ε3/ε3 carriers adjusting for confounders including age and Alzheimer's neuropathology. RESULTS: Three hundred forty-two individuals (24.7%; ∼87.7 years at death; 39.9% nondemented) were ε3/ε4 or ε4/ε4, and 180 (13.0%; ∼89.9 years at death; 66.6% nondemented) were ε2/ε3 or ε2/ε2. ε4 carriers had higher odds of macroinfarcts (odds ratio = 1.41, 95% confidence interval: 1.02-1.94, P = .03), whereas ε2 carriers had higher odds of moderate-to-severe arteriolosclerosis (odds ratio = 1.68, 95% confidence interval: 1.15-2.45, P = .006) compared to ε3/ε3 carriers. Age-stratified analyses suggested that these relationships were driven by ε4 carriers <90 years at death and ε2 carriers ≥90 years at death, respectively. DISCUSSION: APOE differentially affects type and timing of CVD-related neuropathology.

13.
Alzheimers Dement ; 2018 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-30195482

RESUMO

INTRODUCTION: The trends in prevalence and incidence of Alzheimer's disease (AD) dementia remain uncertain. METHODS: A sample of 2794 participants with a clinical diagnosis for AD dementia were included. RESULTS: The 2010 census standardized prevalence of AD dementia was 14.5% (95% CI = 13.7-15.3), and annual incidence was 2.3% (1.7-2.9). Both prevalence and incidence showed substantial variation over time, but no secular trends. The prevalence of AD dementia did not change significantly from 14.6% (95% CI = 13.0, 16.2) in 1994-1997 to 14.7% (95% CI = 13.2, 16.2) in 2010-2012 (P = .84). The annual incidence of AD dementia was 2.8% (95% CI = 2.2, 3.2) in 1998-2000 and 2.2% (95% CI = 1.6, 2.8) in 2004-2006 (P = .20) and remained steady in 2010-2012. The prevalence and incidence among African Americans were approximately twice than those among European Americans. CONCLUSIONS: The prevalence and incidence of AD dementia showed substantial variation between 1994 and 2012, but no secular trend.

14.
PLoS Med ; 15(9): e1002647, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30180184

RESUMO

BACKGROUND: There are few data concerning the association between season and cognition and its neurobiological correlates in older persons-effects with important translational and therapeutic implications for the diagnosis and treatment of Alzheimer disease (AD). We aimed to measure these effects. METHODS AND FINDINGS: We analyzed data from 3,353 participants from 3 observational community-based cohort studies of older persons (the Rush Memory and Aging Project [MAP], the Religious Orders Study [ROS], and the Minority Aging Research Study [MARS]) and 2 observational memory-clinic-based cohort studies (Centre de Neurologie Cognitive [CNC] study at Lariboisière Hospital and the Sunnybrook Dementia Study [SDS]). We performed neuropsychological testing and, in subsets of participants, evaluated cerebrospinal fluid AD biomarkers, standardized structured autopsy measures, and/or prefrontal cortex gene expression by RNA sequencing. We examined the association between season and these variables using nested multiple linear and logistic regression models. There was a robust association between season and cognition that was replicated in multiple cohorts (amplitude = 0.14 SD [a measure of the magnitude of seasonal variation relative to overall variability; 95% CI 0.07-0.23], p = 0.007, in the combined MAP, ROS, and MARS cohorts; amplitude = 0.50 SD [95% CI 0.07-0.66], p = 0.017, in the SDS cohort). Average composite global cognitive function was higher in the summer and fall compared to winter and spring, with the difference equivalent in cognitive effect to 4.8 years' difference in age (95% CI 2.1-8.4, p = 0.002). Further, the odds of meeting criteria for mild cognitive impairment or dementia were higher in the winter and spring (odds ratio 1.31 [95% CI 1.10-1.57], p = 0.003). These results were robust against multiple potential confounders including depressive symptoms, sleep, physical activity, and thyroid status and persisted in cases with AD pathology. Moreover, season had a marked effect on cerebrospinal fluid Aß 42 level (amplitude 0.30 SD [95% CI 0.10-0.64], p = 0.003), which peaked in the summer, and on the brain expression of 4 cognition-associated modules of co-expressed genes (m6: amplitude = 0.44 SD [95% CI 0.21-0.65], p = 0.0021; m13: amplitude = 0.46 SD [95% CI 0.27-0.76], p = 0.0009; m109: amplitude = 0.43 SD [95% CI 0.24-0.67], p = 0.0021; and m122: amplitude 0.46 SD [95% CI 0.20-0.71], p = 0.0012), which were in phase or anti-phase to the rhythms of cognition and which were in turn associated with binding sites for several seasonally rhythmic transcription factors including BCL11A, CTCF, EGR1, MEF2C, and THAP1. Limitations include the evaluation of each participant or sample once per annual cycle, reliance on self-report for measurement of environmental and behavioral factors, and potentially limited generalizability to individuals in equatorial regions or in the southern hemisphere. CONCLUSIONS: Season has a clinically significant association with cognition and its neurobiological correlates in older adults with and without AD pathology. There may be value in increasing dementia-related clinical resources in the winter and early spring, when symptoms are likely to be most pronounced. Moreover, the persistence of robust seasonal plasticity in cognition and its neurobiological correlates, even in the context of concomitant AD pathology, suggests that targeting environmental or behavioral drivers of seasonal cognitive plasticity, or the key transcription factors and genes identified in this study as potentially mediating these effects, may allow us to substantially improve cognition in adults with and without AD.

15.
Artigo em Inglês | MEDLINE | ID: mdl-30102393

RESUMO

Objective: To test whether race (specifically Black or White) moderates the relationship between memory complaints and depressive symptoms in cognitively normal older adults, and if these relationships vary by memory complaint characteristics. Methods: Data from Black (n = 551) and White (n = 1158) cognitively intact participants (Mage = 77.1, SD = 7.5; 76.6% female) in the Minority Aging Research Study and the Rush Memory and Aging Project were used. Participants completed annual clinical evaluations, including the Center for Epidemiologic Studies Depression scale and two memory complaint questions, over periods of up to 18 years. Ordinal mixed effects models were used to examine within-person relationships between memory complaints and depressive symptoms over time, as well as whether race moderated these associations. Results: Reports of greater memory change over time were associated with more depressive symptoms for both Black and White older adults. However, reports of greater frequency of memory problems were related to depressive symptoms for Black older adults only. Conclusion: Findings suggest differential associations between memory complaints and depressive symptoms in cognitively normal Black and White older adults and call for future research to examine the influence of race and related factors on memory complaints and depressive symptoms.

16.
Neuropsychology ; 32(8): 931-940, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30047756

RESUMO

OBJECTIVE: To assess the prevalence, antecedents, and consequences of unawareness of memory impairment in dementia. METHOD: Persons (n = 1,862) from a geographically defined community without dementia at enrollment subsequently underwent clinical classification (248 with dementia, 611 with mild cognitive impairment, 1,003 with no cognitive impairment), memory testing, and self-appraisal of memory. Memory performance was regressed on self-appraised memory, and the residuals served as an index of memory awareness. After clinical classification, participants completed brief cognitive testing at 3-year intervals for up to 15 years. RESULTS: When unawareness was defined as a score at or below thresholds ranging from the 15th to 25th percentiles, it was more common in dementia (67%-83%) and mild cognitive impairment (15%-33%) than in no cognitive impairment (2%-6%; all p < .001). A continuous measure of awareness (M = 0.00, SD = 0.61) was reduced by 0.37-unit in mild cognitive impairment (SE = 0.04, p < .001) and 1.04-unit in dementia (SE = 0.06), p < .001) compared with those without cognitive impairment, and these associations were weaker in Black persons than White persons (estimate for dementia by race = 0.37, SE = 0.12, p = .003; estimate for mild cognitive impairment by race = 0.30, SE = 0.08, p < .001). Higher premorbid neuroticism was associated with better memory awareness in dementia. Higher memory awareness was not related to mortality in mild cognitive impairment or dementia but had a marginal association with slower cognitive decline in mild cognitive impairment. CONCLUSIONS: Unawareness of memory impairment is a common manifestation of dementia, particularly in White persons, but is not strongly related to adverse disease outcomes. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

17.
Neurology ; 91(6): e517-e525, 2018 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-29997190

RESUMO

OBJECTIVE: To examine associations of average and change in late-life blood pressure (BP) with cerebrovascular and Alzheimer disease (AD) neuropathology in a large group of decedents followed longitudinally in vivo. METHODS: This clinical-pathologic study was derived from prospective, community-based cohort studies of aging with similar design and data collection. Measurements of systolic BP (SBP) and diastolic BP (DBP) were obtained annually (mean follow-up 8 years, SD = 4.8). Postmortem neuropathologic evaluations documented diseases of aging. Using regression analyses, we examined associations of average and decline in late-life SBP, and separately in DBP, with neuropathology. RESULTS: In 1,288 persons (mean age at death = 88.6 years; 65% women), the mean standardized person-specific SBP across the study was 134 (SD = 13) and DBP was 71 (SD = 8) mm Hg. The odds of brain infarcts were increased for participants with a higher mean SBP. Specifically, a person with a 1 SD SBP above the mean (147 vs 134 mm Hg) would have a 46% increased odds of having one or more infarcts, and an increased odds of gross infarct (46%) and microinfarct (36%). Furthermore, a more rapidly declining SBP slope over time increased the odds of one or more infarcts. Mean DBP, not slope, was related to brain infarcts. AD pathology analyses showed an association of a higher mean SBP with higher number of tangles (p = 0.038) but not plaques or other pathology (all p > 0.06). Changes in BP were not significantly related to AD pathology. CONCLUSIONS: Higher average late-life SBP and DBP, and independently a faster decline in SBP, are associated with increasing number of brain infarcts, including gross and microinfarcts. We found some evidence for a relation of SBP with AD, specifically tangles. Both average and decline in BP are related to brain disease.

18.
Acta Neuropathol ; 136(6): 857-872, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29967939

RESUMO

Cerebrospinal fluid (CSF) levels of amyloid-ß 42 (Aß42) and tau have been evaluated as endophenotypes in Alzheimer's disease (AD) genetic studies. Although there are sex differences in AD risk, sex differences have not been evaluated in genetic studies of AD endophenotypes. We performed sex-stratified and sex interaction genetic analyses of CSF biomarkers to identify sex-specific associations. Data came from a previous genome-wide association study (GWAS) of CSF Aß42 and tau (1527 males, 1509 females). We evaluated sex interactions at previous loci, performed sex-stratified GWAS to identify sex-specific associations, and evaluated sex interactions at sex-specific GWAS loci. We then evaluated sex-specific associations between prefrontal cortex (PFC) gene expression at relevant loci and autopsy measures of plaques and tangles using data from the Religious Orders Study and Rush Memory and Aging Project. In Aß42, we observed sex interactions at one previous and one novel locus: rs316341 within SERPINB1 (p = 0.04) and rs13115400 near LINC00290 (p = 0.002). These loci showed stronger associations among females (ß = - 0.03, p = 4.25 × 10-8; ß = 0.03, p = 3.97 × 10-8) than males (ß = - 0.02, p = 0.009; ß = 0.01, p = 0.20). Higher levels of expression of SERPINB1, SERPINB6, and SERPINB9 in PFC was associated with higher levels of amyloidosis among females (corrected p values < 0.02) but not males (p > 0.38). In total tau, we observed a sex interaction at a previous locus, rs1393060 proximal to GMNC (p = 0.004), driven by a stronger association among females (ß = 0.05, p = 4.57 × 10-10) compared to males (ß = 0.02, p = 0.03). There was also a sex-specific association between rs1393060 and tangle density at autopsy (pfemale = 0.047; pmale = 0.96), and higher levels of expression of two genes within this locus were associated with lower tangle density among females (OSTN p = 0.006; CLDN16 p = 0.002) but not males (p ≥ 0.32). Results suggest a female-specific role for SERPINB1 in amyloidosis and for OSTN and CLDN16 in tau pathology. Sex-specific genetic analyses may improve understanding of AD's genetic architecture.

19.
Neurol Neuroimmunol Neuroinflamm ; 5(4): e467, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29904644

RESUMO

Objective: HIV infection sets off an immediate immune response and inflammatory cascade that can lead to neuronal injury and cognitive impairment, but the relationship between immune markers, regional brain volumes, and cognition remains understudied in HIV-infected adults. Methods: Cross-sectional associations were examined between serum immune markers of activation (neopterin) and inflammation (interleukin [IL]-1ß, IL-6, tumor necrosis factor alpha, and C-reactive protein) with regional brain volumes (cortical, subcortical, total gray matter, hippocampus, and subfields) and cognition in 66 HIV-infected, virally suppressed, adults who underwent 3.0-T MRI as part of the Research Core of the Rush Center of Excellence on Disparities in HIV and Aging. Immune markers were assayed from frozen plasma, values were entered into linear regression models as predictors of regional brain volumes, and interactive effects of immune response and regional brain volumes on cognition were examined. Results: No inflammatory marker was associated with any regional brain volume. Higher neopterin level was associated with lower total hippocampal, presubiculum, and cornu ammonis (CA) subfield volumes. Higher neopterin level and lower total hippocampal volume were independently associated with lower episodic memory, and neopterin level fully mediated the effect of hippocampal atrophy on episodic memory. Higher neopterin levels were associated with lower presubiculum, CA1, and CA4/dentate volumes and lower semantic memory, working memory, and global cognition. Conclusion: Immune activation in response to HIV infection, measured by neopterin, has a deleterious and targeted effect on regional brain structure, which can be visualized with clinically available MRI measures of hippocampus and its subfields, and this effect is associated with lower cognitive function.

20.
Alzheimers Dement ; 14(9): 1171-1183, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29907423

RESUMO

INTRODUCTION: Precision medicine methodologies and approaches have advanced our understanding of the clinical presentation, development, progression, and management of Alzheimer's disease (AD) dementia. However, sex and gender have not yet been adequately integrated into many of these approaches. METHODS: The Society for Women's Health Research Interdisciplinary Network on AD, comprised of an expert panel of scientists and clinicians, reviewed ongoing and published research related to sex and gender differences in AD. RESULTS: The current review is a result of this Network's efforts and aims to: (1) highlight the current state-of-the-science in the AD field on sex and gender differences; (2) address knowledge gaps in assessing sex and gender differences; and (3) discuss 12 priority areas that merit further research. DISCUSSION: The exclusion of sex and gender has impeded faster advancement in the detection, treatment, and care of AD across the clinical spectrum. Greater attention to these differences will improve outcomes for both sexes.

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