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1.
J Alzheimers Dis ; 2021 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-33935076

RESUMO

BACKGROUND: Self-reported discrimination is a source of psychosocial stress that has been previously associated with poor cognitive function in older African Americans without dementia. OBJECTIVE: Here, we examine the association of discrimination with dementia and cognitive impairment in racially diverse older Brazilians. METHODS: We included 899 participants 65 years or older (34.3% Black) from the Pathology, Alzheimer's and Related Dementias Study (PARDoS), a community-based study of aging and dementia. A structured interview with informants of the deceased was conducted. The interview included the Clinical Dementia Rating (CDR) Scale for the diagnosis of dementia and cognitive impairment proximate to death and the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) as a second measure of cognitive impairment. Informant-reported discrimination was assessed using modified items from the Major and Everyday Discrimination Scales. RESULTS: Discrimination was reported by informants of 182 (20.2%) decedents and was more likely reported by informants of Blacks than Whites (25.3% versus 17.6%, p = 0.006). Using the CDR, a higher level of informant-reported discrimination was associated with higher odds of dementia (OR: 1.24, 95% CI 1.08 -1.42, p = 0.002) and cognitive impairment (OR: 1.21, 95% CI: 1.06 -1.39, p = 0.004). Similar results were observed using the IQCODE (estimate: 0.07, SE: 0.02, p = 0.003). The effects were independent of race, sex, education, socioeconomic status, major depression, neuroticism, or comorbidities. CONCLUSION: Higher level of informant-reported discrimination was associated with higher odds of dementia and cognitive impairment in racially diverse older Brazilians.

2.
Acta Neuropathol Commun ; 9(1): 71, 2021 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-33858515

RESUMO

Insulin is an important hormone for brain function, and alterations in insulin metabolism may be associated with neuropathology. We examined associations of molecular markers of brain insulin signaling with cerebrovascular disease. Participants were enrolled in the Religious Orders Study (ROS), an ongoing epidemiologic community-based, clinical-pathologic study of aging from across the United States. Using cross-sectional analyses, we studied a subset of ROS: 150 persons with or without diabetes, matched 1:1 by sex on age-at-death and education. We used ELISA, immunohistochemistry, and ex vivo stimulation with insulin, to document insulin signaling in postmortem midfrontal gyrus cortex tissue. Postmortem neuropathologic data identified cerebrovascular disease including brain infarcts, classified by number (as none for the reference; one; and more than one), size (gross and microscopic infarcts), and brain region/location (cortical and subcortical). Cerebral vessel pathologies were assessed, including severity of atherosclerosis, arteriolosclerosis, and amyloid angiopathy. In separate regression analyses, greater AKT1 phosphorylation at T308 following ex vivo stimulation with insulin (OR = 1.916; estimate = 0.650; p = 0.007) and greater pS616IRS1 immunolabeling in neuronal cytoplasm (OR = 1.610; estimate = 0.476; p = 0.013), were each associated with a higher number of brain infarcts. Secondary analyses showed consistent results for gross infarcts and microinfarcts separately, but no other association including by infarct location (cortical or subcortical). AKT S473 phosphorylation following insulin stimulation was associated with less amyloid angiopathy severity, but not with other vessel pathology including atherosclerosis and arteriolosclerosis. In summary, insulin resistance in the human brain, even among persons without diabetes, is associated with cerebrovascular disease and especially infarcts. The underlying pathophysiologic mechanisms need further elucidation. Because brain infarcts are known to be associated with lower cognitive function and dementia, these data are relevant to better understanding the link between brain metabolism and brain function.

3.
Neurology ; 2021 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-33853892

RESUMO

OBJECTIVE: We tested the hypothesis that an inverse association exists between diabetes mellitus (DM) and hemoglobin A1C (A1C) with Transactive response DNA binding protein 43 (TDP-43) levels in older adults. METHODS: We leveraged antemortem and postmortem data of decedents from three community-based clinical-pathological studies. DM status, A1C levels, and medications for DM were documented annually. TDP-43 cytoplasmic inclusions, evaluated in 6 brain regions using immunohistochemistry, were used to obtain a semiquantitative TDP-43 score (0-5) in each region, and scores were averaged across regions to obtain a TDP-43 severity score. We used linear regressions to test the association of DM and A1C with the TDP-43 severity score. RESULTS: On average, participants (n=817) were 90 years old at the time of death, three fourth were women, and one fourth had DM. The mean A1C was 6.0% (SD=0.6). TDP-43 was observed in 54% of participants, and the mean TDP-43 score was 0.7 (range 0-4.5). A higher level of A1C was associated with a lower TDP-43 score (estimate=-0.156, S.E.=0.060, p=0.009) while DM had a borderline inverse association with the TDP-43 score (estimate=-0.163, S.E.=0.087, p=0.060). The association of higher levels of A1C with lower TDP-43 scores persisted after further adjustment by Apolipoprotein ε4, vascular risk factors, stroke, and hypoglycemic medications. Exclusion of the oldest old participants did not change the results. CONCLUSION: Overall, the results suggest that a high level of A1C is associated with less TDP-43 proteinopathy in older persons while the relationship of DM with TDP-43 needs further study.

4.
Stroke ; : STROKEAHA120030226, 2021 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-33840227

RESUMO

BACKGROUND AND PURPOSE: The general cardiovascular Framingham risk score (FRS) identifies adults at increased risk for stroke. We tested the hypothesis that baseline FRS is associated with the presence of postmortem cerebrovascular disease (CVD) pathologies. METHODS: We studied the brains of 1672 older decedents with baseline FRS and measured CVD pathologies including macroinfarcts, microinfarcts, atherosclerosis, arteriolosclerosis, and cerebral amyloid angiopathy. We employed a series of logistic regressions to examine the association of baseline FRS with each of the 5 CVD pathologies. RESULTS: Average age at baseline was 80.5±7.0 years and average age at death was 89.2±6.7 years. A higher baseline FRS was associated with higher odds of macroinfarcts (odds ratio, 1.10 [95% CI, 1.07-1.13], P<0.001), microinfarcts (odds ratio, 1.04 [95% CI, 1.01-1.07], P=0.009), atherosclerosis (odds ratio, 1.07 [95% CI, 1.04-1.11], P<0.001), and arteriolosclerosis (odds ratio, 1.04 [95% CI, 1.01-1.07], P=0.005). C statistics for these models ranged from 0.537 to 0.595 indicating low accuracy for predicting CVD pathologies. FRS was not associated with the presence of cerebral amyloid angiopathy. CONCLUSIONS: A higher FRS score in older adults is associated with higher odds of some, but not all, CVD pathologies, with low discrimination at the individual level. Further work is needed to develop a more robust risk score to identify adults at risk for accumulating CVD pathologies.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33377540

RESUMO

OBJECTIVE: Exposure to negative life events (NLEs) and neuroticism are associated with dementia. It is unknown whether neuroticism explains or modifies the association of NLEs with dementia in older Black and White Brazilians. METHODS: A total of 1747 decedents 65 years and older White and Black (11% Black and 23% Mixed) Brazilians, 53% women, were included in the analyses. Data were obtained in a face-to-face interview with an informant (71% their children) who knew the decedents for 47 years on average. Dementia was classified using the Clinical Dementia Rating. NLEs were assessed with a 10-item scale involving common problems (e.g., death, illness, alcoholism, and financial). Neuroticism was assessed with a 6-item neuroticism scale adapted from the NEO Five-Factor Inventory. Models adjusted for age, sex, and education. Black and mixed-race were combined in the analyses. RESULTS: NLEs (median of 2) were more common in Blacks than Whites (2.04 vs. 1.82, p = 0.007). More NLEs increased the odds of dementia (OR = 1.112, ß = 0.106, p = 0.002), similarly in Blacks and Whites (ßinteraction  = 0.046, p = 0.526). More NLEs were also associated with higher neuroticism (ß = 0.071, p < 0.0001), in Whites but not in Blacks (ßinteraction  = -0.048, p = 0.006). Neuroticism was associated with higher odds of dementia (OR = 1.658, ß = 0.506, p=<0.001), in Whites but not in Blacks (ßinteraction  = -0.420, p = 0.040). Overall, 34% of the effect of NLEs on dementia was associated with the underlying neuroticism trait in Whites (65%, Indirect OR = 1.060, p < 0.001) but no association was evident in Blacks (6%, Indirect OR = 1.008, p = 0.326). Neuroticism did not moderate the association of NLEs with dementia (OR = 0.979, ß = -0.021, p = 0.717). CONCLUSION: The association of NLEs and dementia is partially explained by neuroticism in older White but not in Blacks Brazilians.

6.
J Alzheimers Dis ; 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33185594

RESUMO

BACKGROUND: Vascular mechanisms may contribute to the accumulation of AD pathology. OBJECTIVE: We examined whether the burden of vascular risk factors proximate to death is associated with amyloid-ß and tau levels or modified their known association. METHODS: We examined the brains of 1, 585 participants from two longitudinal community-based studies of older adults. Amyloid-ß and tau were quantified by postmortem examination. The burden of vascular risk factors was summarized by calculating the Framingham general cardiovascular risk score (FRS) proximate to death. Using linear regressions, we examined the association of the FRS with the amyloid-ß and tau levels and examined if the FRS modified the association of the amyloid-ß with tau. RESULTS: On average, participants were nearly 90 years old and two-thirds were women. The FRS was not associated with amyloid-ß (Spearman r  = -0.00, p  = 0.918) or tau (r = 0.01, p = 0.701). However, the FRS as a whole (estimate = -0.022, SE = 0.008, p = 0.009), and specifically the systolic blood pressure (SBP) component (estimate = -0.033, SE = 0.012, p = 0.009), modified the association of the amyloid-ß with tau. Further analysis showed that the association between amyloid-ß and tau was stronger at lower levels of SBP. CONCLUSION: Late-life vascular risk scores were not related to postmortem levels of amyloid-ß or tau. However, lower levels of vascular risk scores and SBP were associated with a stronger association between amyloid-ß and tau. These data suggest that vascular risk factors may modify the relation of AD pathology markers to one another.

7.
J Am Geriatr Soc ; 68(11): 2662-2667, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32978794

RESUMO

BACKGROUND/OBJECTIVES: The purpose of this study was to: (1) examine relationships between body mass index (BMI) stability and cognitive decline in older African Americans; and (2) investigate differences in the relationships between women and men. DESIGN: The present study is a secondary data analysis of the Minority Aging Research Study, which is a longitudinal, cohort study of risk factors for cognitive decline and Alzheimer's disease among older African Americans living in the Chicago, IL, area. The study entails annual clinical evaluations, including measures of 19 neuropsychological tests that represent five cognitive domains, including episodic, semantic, and working memory, perceptual speed, and visuospatial ability. PARTICIPANTS: Participants (n = 671; mean age = 73.5 years; standard deviation = 6.2 years) were included in the present analysis if they were dementia free at baseline and completed at least two clinical evaluations, on average 1 year apart, that included valid cognitive and BMI assessments. RESULTS: Mixed-effects models showed higher baseline BMI was related to slower global cognitive decline, whereas changes in BMI (instability) were related to faster global cognitive decline. These effects were the same for four of five cognitive domains and remained after controlling for various health characteristics. However, women and men did not differ in any of the relationships. CONCLUSION: Higher BMI is related to slower cognitive decline in older African Americans, but greater BMI instability is related to faster decline. Stability of BMI should be considered in the cognitive aging of African Americans.

8.
Ann Neurol ; 88(3): 513-525, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32557841

RESUMO

OBJECTIVE: To examine associations of molecular markers of brain insulin signaling with Alzheimer disease (AD) and cognition among older persons with or without diabetes. METHODS: This clinical-pathologic study was derived from a community-based cohort study, the Religious Orders Study. We studied 150 individuals (mean age at death =87 years, 48% women): 75 with and 75 without diabetes (matched by sex on age at death and education). Using enzyme-linked immunosorbent assay, immunohistochemistry, and ex vivo stimulation of brain tissue with insulin, we assessed insulin signaling in the postmortem middle frontal gyrus cortex. Postmortem data documented AD neuropathology. Clinical evaluations documented cognitive function proximate to death, based on 17 neuropsychological tests. In adjusted regression analyses, we examined associations of brain insulin signaling with diabetes, AD, and level of cognition. RESULTS: Brain insulin receptor substrate-1 (IRS1) phosphorylation (pS307 IRS1/total IRS1) and serine/threonine-protein kinase (AKT) phosphorylation (pT308 AKT1/total AKT1) were similar in persons with or without diabetes. AKT phosphorylation was associated with the global AD pathology score (p = 0.001). In contrast, IRS1 phosphorylation was not associated with AD (p = 0.536). No other associations of insulin signaling were found with the global AD score, including when using the ex vivo brain insulin stimulation method. In secondary analyses, normalized pT308 AKT1 was positively correlated with both the amyloid burden and tau tangle density, and no other associations of brain insulin signaling with neuropathology were observed. Moreover, normalized pT308 AKT1 was associated with a lower level of global cognitive function (estimate = -0.212, standard error = 0.097; p = 0.031). INTERPRETATION: Brain AKT phosphorylation, a critical node in the signaling of insulin and other growth factors, is associated with AD neuropathology and lower cognitive function. ANN NEUROL 2020;88:513-525.

9.
J Assoc Nurses AIDS Care ; 31(3): 268-278, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31725106

RESUMO

The purpose of our review was to analyze evidence related to physical activity (PA) and cognitive health in people living with HIV (PLWH), appraise psychometric characteristics of study measures, and calculate effect sizes. A computerized database search of the literature published between 1996 and 2017 was examined for correlational and observational studies that included a sample of PLWH, measured PA, and measured cognitive health. Seven articles met the sampling criteria. Of which, six studies used a cross-sectional design; one used a longitudinal design. All but one found significant positive associations between PA and cognitive health in PLWH. Four studies showed a moderate to high effect for PA on cognitive function (Cohen's d values = 0.45-0.58). None reported sample-specific reliability and validity estimates for PA and cognitive health instruments. PA is a modifiable factor that may delay the onset of cognitive impairment and decline among PLWH.


Assuntos
Cognição/fisiologia , Depressão/prevenção & controle , Exercício Físico/psicologia , Infecções por HIV/psicologia , Aptidão Física/psicologia , Adaptação Psicológica , Depressão/psicologia , Humanos , Qualidade de Vida
10.
J Gerontol B Psychol Sci Soc Sci ; 75(4): 783-791, 2020 03 09.
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 = 1,158) 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.


Assuntos
Afro-Americanos/estatística & dados numéricos , Envelhecimento/etnologia , Transtornos Cognitivos/etnologia , Depressão/etnologia , Grupo com Ancestrais do Continente Europeu/estatística & dados numéricos , Transtornos da Memória/etnologia , Afro-Americanos/psicologia , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/psicologia , Cognição , Depressão/psicologia , Grupo com Ancestrais do Continente Europeu/psicologia , Feminino , Humanos , Masculino , Transtornos da Memória/psicologia , Fatores de Risco , Autorrelato
11.
Ann Neurol ; 86(6): 844-852, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31614018

RESUMO

OBJECTIVE: To test the hypothesis that Alzheimer's disease and related neuropathologies contribute to the association between hospitalization and cognitive decline in old age. METHODS: As part of a longitudinal clinical-pathologic cohort study, 526 older persons (mean age at death = 90.9 years, 71% female) without dementia at baseline completed annual cognitive testing and were autopsied at death. Hospitalization information was obtained from linked Medicare claims records. Neuropathologic examination assessed ß-amyloid burden, tau tangle density, neocortical Lewy bodies, hippocampal sclerosis, chronic gross and microscopic cerebral infarcts, and transactive response DNA binding protein 43 kDa. RESULTS: Over a mean of 5.1 years, a total of 1,383 hospitalizations occurred, and the mean annual rate of hospitalization was 0.5 (standard deviation = 0.6, median = 0.4). Higher rate of hospitalization was not directly related to higher burden for any of the neuropathologic markers. Higher rate of hospitalization was associated with more rapid cognitive decline (estimate = -0.042, standard error [SE] = 0.012, p < 0.001), and after controlling for all 7 neuropathologic markers, the association was essentially the same (estimate = -0.040, SE = 0.013, p = 0.002). In a multivariable model with 3-way interactions of neuropathologic markers with hospitalization rate and time, the association between hospitalization rate and faster cognitive decline was greater in persons with more tangle pathology (estimate for interaction = -0.007, SE = 0.002, p = 0.002) and in persons with neocortical Lewy bodies (estimate for interaction = -0.117, SE = 0.042, p = 0.005). INTERPRETATION: Older persons with more hospitalizations experienced faster rates of cognitive decline, and this association was more pronounced in persons with more tau tangle density and with neocortical Lewy body pathologies. ANN NEUROL 2019;86:844-852.


Assuntos
Envelhecimento/patologia , Doença de Alzheimer/epidemiologia , Doença de Alzheimer/patologia , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/patologia , Hospitalização/tendências , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/psicologia , Doença de Alzheimer/psicologia , Disfunção Cognitiva/psicologia , Estudos de Coortes , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Masculino , Medicare/tendências , Doenças do Sistema Nervoso/epidemiologia , Doenças do Sistema Nervoso/patologia , Doenças do Sistema Nervoso/psicologia , Estados Unidos/epidemiologia
12.
Neurobiol Aging ; 84: 119-130, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31539648

RESUMO

Aberrant insulin and adipokine signaling has been implicated in cognitive decline associated with both type 2 diabetes mellitus and neurodegenerative diseases. We established methods that reliably measure insulin, adiponectin and leptin signaling, and their crosstalk, in thawed postmortem mid-frontal cortical tissue from cognitively normal older subjects with a short postmortem interval. Insulin-evoked insulin receptor (IR) activation increases activated, tyrosine-phosphorylated IRß on tyrosine residues 960, 1150, and 1151, insulin receptor substrate-1 recruitment to IRß and phosphorylated RAC-α-serine/threonine-protein kinase. Adiponectin augments, but leptin inhibits, insulin signaling. Adiponectin activates adiponectin receptors to induce APPL1 binding to adiponectin receptor 1 and 2 and T-cadherin and downstream adenosine monophosphate-dependent protein kinase phosphorylation. Insulin inhibited adiponectin-induced signaling. In addition, leptin-induced leptin receptor (OB-R) signaling promotes Janus kinase 2 recruitment to OB-R and Janus kinase 2 and downstream signal transducer and activator of transcription 3 phosphorylation. Insulin enhanced leptin signaling. These data demonstrate insulin and adipokine signaling interactions in human brain. Future studies can use these methods to examine insulin, adiponectin, and leptin metabolic dysregulation in aging and disease states, such as type 2 diabetes and Alzheimer's disease-related dementias.


Assuntos
Adipocinas/metabolismo , Encéfalo/patologia , Insulina/metabolismo , Transdução de Sinais , Envelhecimento/metabolismo , Encéfalo/metabolismo , Humanos , Leptina/metabolismo , Mudanças Depois da Morte
13.
Neuroepidemiology ; 53(1-2): 100-107, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31067547

RESUMO

BACKGROUND: Few data are available on associations of antiphospholipid (aPL) antibodies with cognitive and motor decline in aging, and cerebrovascular disease on in vivo neuroimaging and postmortem neuropathology. METHODS: This longitudinal, clinical-pathologic study (aPL antibodies, brain infarcts, and cognitive and motor decline in aging), was derived from 2 ongoing community-based cohort studies. A panel of 3 aPL antibodies was assayed in serum from 956 older individuals (mean age = 81.1 years; 72% women). Serum was also tested in a subset for markers of inflammation (C-reactive protein [CRP]) and blood-brain barrier breakdown (matrix metalloproteinases, MMPs). Annual clinical evaluations documented cognitive (17 neuropsychological tests) and motor function including parkinsonism. Cerebrovascular disease data were derived from in vivo neuroimaging and postmortem neuropathologic evaluations (699 individuals). We examined associations of aPL with cognitive and motor decline, other serum markers, neuroimaging, and neuropathology. RESULTS: Of 956 individuals, 197 (20.6%) had aPL positivity, defined as positivity on any of the assays, at the time of first measurement. During a mean follow-up of 6.6 years (SD 4), overall aPL positivity was not associated with change in global cognition (estimate = -0.005, SE 0.011; p = 0.622) or parkinsonian signs (estimate = -0.003, SE 0.017; p = 0.860). aPL were not associated with serum CRP or MMPs (both p > 0.268). aPL were not associated with in vivo brain magnetic resonance imaging white matter hyperintensities or infarcts (both p > 0.376). Among those autopsied, aPL were not associated with pathologically confirmed brain infarcts, or cerebral atherosclerosis or arteriolosclerosis (all p≥ 0.447). CONCLUSIONS: In older individuals followed longitudinally, aPL do not relate to cognitive or motor decline, inflammation, or cerebrovascular disease on in vivo neuroimaging or postmortem neuropathology.


Assuntos
Anticorpos Antifosfolipídeos/sangue , Disfunção Cognitiva/sangue , Disfunção Cognitiva/diagnóstico por imagem , Transtornos Motores/sangue , Transtornos Motores/diagnóstico por imagem , Neuroimagem/métodos , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Estudos de Coortes , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Masculino , Neuropatologia
15.
J Affect Disord ; 250: 313-318, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30875674

RESUMO

BACKGROUND: Brain proteins, including Insulin-like Growth Factor Binding Protein 5 (IGFBP-5), have been associated with cognitive dysfunction in aging. Mechanisms linking depression with cognition are poorly understood. We hypothesize that the association of depressive symptoms with cognition is mediated or modified by brain proteins. METHODS: IGFBP-5, HSPB2, AK4, ITPK1 and PLXNB1 were measured in dorsolateral prefrontal cortex in 1057 deceased participants, who underwent annual assessments of depressive symptoms and cognition for a mean of 8.9 years. The average number of depressive symptoms per year before a dementia diagnosis was calculated for each person. RESULTS: A one standard deviation above the mean IGFBP-5 was associated with a 14% higher odds of having more depressive symptoms (p < 0.031). Higher IGFBP-5 was associated with faster decline in global cognition (p < 0.001) and five cognitive domains (p < 0.008), controlling for depressive symptoms. IGFBP-5 moderated the association of depressive symptoms with decline in global cognition (p = 0.045). IGFBP-5 mediated ten percent or less of the total effect of depressive symptoms on decline in global cognition and the cognitive domains (p > 0.070). LIMITATIONS: Participants were volunteers and self-selection bias limits the generalizability of our findings. In addition, we used self-reported data on depressive symptoms. However, we also used data on depression medications as sensitivity analyses to confirm findings. CONCLUSIONS: In old age, brain IGFBP-5 is associated with depressive symptoms and cognition. The association of depressive symptoms with cognitive decline is conditional on IGFBP-5.


Assuntos
Encéfalo/metabolismo , Transtornos Cognitivos/metabolismo , Transtorno Depressivo/metabolismo , Proteína 5 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Idoso , Idoso de 80 Anos ou mais , Transtornos Cognitivos/psicologia , Transtorno Depressivo/psicologia , Feminino , Proteínas de Choque Térmico HSP27/metabolismo , Humanos , Masculino , Córtex Pré-Frontal , Proteômica
16.
Neurology ; 92(8): e831-e840, 2019 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-30674595

RESUMO

OBJECTIVE: To assess whether neurodegenerative pathologies are differentially related to trajectories of change in different cognitive abilities. METHODS: At annual intervals for up to 21 years, 915 older participants in a longitudinal clinical-pathologic cohort study completed a battery of 15 tests from which previously established composite measures of episodic memory, semantic memory, working memory, and perceptual speed were derived. At death, they underwent a neuropathologic examination to quantify Alzheimer disease pathology, Lewy bodies, transactive response DNA-binding protein 43 (TDP-43) pathology, and hippocampal sclerosis plus multiple markers of cerebrovascular disease. Time-varying effect models were used to assess change over time in the relation of neuropathologic markers to cognitive trajectories. RESULTS: Controlling for pathology, decline in perceptual speed was evident about 15 years before death; modest decline in semantic and working memory occurred later; and there was little change in episodic memory. Each neurodegenerative marker was associated with lower episodic memory function beginning about 10 to 16 years before death. As time before death decreased, Alzheimer disease pathology, Lewy bodies, and hippocampal sclerosis were associated with impairment in other cognitive domains but the association of TDP-43 pathology with cognition continued to be mainly confined to episodic memory. CONCLUSIONS: The results suggest that episodic memory impairment is an early sign of multiple neurodegenerative conditions, which primarily differ in their associations with other cognitive systems.


Assuntos
Encéfalo/patologia , Disfunção Cognitiva/fisiopatologia , Memória Episódica , Memória de Curto Prazo , Percepção , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/patologia , Autopsia , Encéfalo/metabolismo , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/patologia , Proteínas de Ligação a DNA/metabolismo , Progressão da Doença , Feminino , Hipocampo/patologia , Humanos , Corpos de Lewy/patologia , Estudos Longitudinais , Masculino , Testes Neuropsicológicos , Esclerose
17.
Neurology ; 92(7): e690-e699, 2019 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-30635482

RESUMO

OBJECTIVE: To determine whether emergent and urgent (nonelective) hospitalizations are associated with faster acceleration of cognitive decline compared to elective hospitalizations, accounting for prehospital decline. METHODS: Data came from the Rush Memory and Aging Project, a prospective cohort study of community-dwelling older persons without baseline dementia. Annual measures of cognition via a battery of 19 tests were linked to 1999 to 2010 Medicare claims records. RESULTS: Of 777 participants, 460 (59.2%) were hospitalized over a mean of 5.0 (SD = 2.6) years; 222 (28.6%) had at least one elective and 418 (53.8%) at least one nonelective hospitalization. Mixed-effects regression models estimated change in global cognition before and after each type of hospitalization compared to no hospitalization, adjusted for age, sex, education, medical conditions, length of stay, surgery, intensive care unit, and comorbidities. Persons who were not hospitalized had a mean loss of 0.051 unit global cognition per year. In comparison, there was no significant difference in rate of decline before (0.044 unit per year) or after (0.048 unit per year) elective hospitalizations. In contrast, decline before nonelective hospitalization was faster (0.076 unit per year; estimate = -0.024, SE = 0.011, p = 0.032), and accelerated by 0.036 unit (SE = 0.005, p < 0.001) to mean loss of 0.112 unit per year after nonelective hospitalizations, more than doubling the rate in those not hospitalized. CONCLUSIONS: Nonelective hospitalizations are related to more dramatic acceleration in cognitive decline compared to elective hospitalizations, even after accounting for prehospital decline. These findings may inform which hospital admissions pose the greatest risk to the cognitive health of older adults.


Assuntos
Disfunção Cognitiva/epidemiologia , Emergências , Hospitalização/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Vida Independente , Masculino , Medicare , Testes de Estado Mental e Demência , Estudos Prospectivos , Estados Unidos/epidemiologia
18.
J Aging Health ; 31(7): 1278-1296, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-29742953

RESUMO

Objective: This study examines the effect of antidepressant medication use and social engagement on the level of depressive symptoms at the time of initially meeting criteria for dementia. Method: Measures of social engagement, medication use, and depressive symptoms from 402 participants with incident dementia were utilized for the study. Proportional odds models adjusted for demographics were constructed with depressive symptoms as the outcome and social network size, perceived social isolation, and antidepressant medication use as independent variables. Results: Each additional person in the social network was associated with a lower depressive symptom score, odds ratio (OR) = 0.93, 95% confidence interval (CI) = [0.90, 0.97], p ≤ .01, and each unit increase in perceived social isolation was associated with a higher depressive symptom score (OR = 4.14, 95% CI = [2.94, 5.85], p ≤ .01). No association was found between antidepressant medication use and depressive symptom score. Discussion: Depression management at the time of dementia diagnosis should probably be directed toward increasing social engagement in older adults.


Assuntos
Afro-Americanos/psicologia , Antidepressivos/uso terapêutico , Demência/psicologia , Depressão/tratamento farmacológico , Depressão/etnologia , Grupo com Ancestrais do Continente Europeu/psicologia , Idoso , Idoso de 80 Anos ou mais , Demência/etnologia , Depressão/psicologia , Feminino , Humanos , Vida Independente , Masculino , Razão de Chances , Isolamento Social
19.
Neurology ; 91(6): e517-e525, 2018 08 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.


Assuntos
Doença de Alzheimer/patologia , Pressão Sanguínea/fisiologia , Encéfalo/patologia , Transtornos Cerebrovasculares/patologia , Hipertensão/patologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/epidemiologia , Transtornos Cerebrovasculares/diagnóstico , Transtornos Cerebrovasculares/epidemiologia , Estudos de Coortes , Feminino , Seguimentos , Humanos , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Masculino , Estudos Prospectivos , Fatores de Risco
20.
Int J Gen Med ; 11: 175-178, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29773952

RESUMO

Background: Remote ischemic preconditioning (RIPC) is a procedure that generates a brief period of ischemia followed by reperfusion. The role of RIPC in protecting myocardial ischemia during hemodialysis is not yet established. The aim of the study was to evaluate RIPC myocardial protection as evaluated by ultrasensitive I troponin in hemodialysis outpatients. Patients and methods: A double-blind randomized trial with two groups: intervention submitted to RIPC and control group without RIPC. Intervention group received RIPC in three consecutive hemodialysis sessions. Blood samples were taken before and after each session. Blood urea nitrogen for calculation of single-pool Kt/v and ultrasensitive I troponin were measured to evaluate dialysis adequacy and myocardial injury. Results: A total of 47 patients were randomized. About 60.8% were men and 54% were diabetic. The mean single-pool Kt/v was 1.51 in the intervention group and 1.49 in control. The ultrasensitive troponin I measured no significant change from the time of collection: before or after dialysis. Conclusion: The RIPC applied in three consecutive sessions did not demonstrate superiority to control, therefore another study tested RIPC in 12 consecutive sessions with a positive result in myocardial protection. In our study, more than half of the patients were diabetic. Diabetic patients have a trend to show a lower response to RIPC because of the greater presence of collateral coronary circulation. In summary, in this model there was no interference of RIPC in ultrasensitive troponin I values, but troponin had a high negative predictive value for myocardial infarction in all tested models.

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