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1.
JAMA Neurol ; 81(3): 233-239, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38315471

RESUMEN

Importance: A healthy lifestyle is associated with better cognitive functioning in older adults, but whether this association is independent of the accumulation of dementia-related pathologies in the brain is uncertain. Objective: To determine the role of postmortem brain pathology, including ß-amyloid load, phosphorylated tau tangles, cerebrovascular pathology, and other brain pathologies, in the association between lifestyle and cognition proximate to death. Design, Setting, and Participants: This cohort study used data from the Rush Memory and Aging Project, a longitudinal clinical-pathologic study with autopsy data from 1997 to 2022 and up to 24 years of follow-up. Participants included 754 deceased individuals with data on lifestyle factors, cognitive testing proximate to death, and a complete neuropathologic evaluation at the time of these analyses. Data were analyzed from January 2023 to June 2023. Exposures: A healthy lifestyle score was developed based on self-reported factors, including noncurrent smoking, at least 150 minutes of physical activity per week, limiting alcohol consumption, a Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet score higher than 7.5, and a late-life cognitive activity score higher than 3.2. The lifestyle score ranges from 0 to 5, with higher scores reflecting a healthier lifestyle. Main Outcomes and Measures: The global cognitive score was derived from a battery of nineteen standardized tests. Brain pathology measures included ß-amyloid load, phosphorylated tau tangles, global Alzheimer disease pathology, vascular brain pathologies, Lewy body, hippocampal sclerosis, and TAR DNA-binding protein 43. Results: Of 586 included decedents, 415 (70.8%) were female, 171 (29.2%) were male, and the mean (SD) age at death was 90.9 (6.0) years. Higher lifestyle score was associated with better global cognitive functioning proximate to death. In the multivariable-adjusted model, a 1-point increase in lifestyle score was associated with 0.216 (SE = 0.036, P < .001) units higher in global cognitive scores. Neither the strength nor the significance of the association changed substantially when common dementia-related brain pathologies were included in the multivariable-adjusted models. The ß estimate after controlling for the ß-amyloid load was 0.191 (SE = 0.035; P < .001). A higher lifestyle score was associated with lower ß-amyloid load in the brain (ß = -0.120; SE = 0.041; P = .003), and 11.6% of the lifestyle-cognition association was estimated through ß-amyloid load. Conclusions and Relevance: This study found that in older adults, a healthy lifestyle may provide a cognitive reserve to maintain cognitive abilities independently of common neuropathologies of dementia.


Asunto(s)
Enfermedad de Alzheimer , Humanos , Masculino , Femenino , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Enfermedad de Alzheimer/patología , Cognición , Encéfalo/patología , Péptidos beta-Amiloides/metabolismo , Estilo de Vida Saludable
2.
J Alzheimers Dis ; 95(2): 407-409, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37545243

RESUMEN

In a recent issue of the Journal of Alzheimer's Disease, Zinman et al. investigated the role of sex in the risk of cognitive impairment in 5,969 patients with a stroke or transient ischemic attacks. Using a short validated clinical screening tool, they noted that men had a 34% higher risk of screening positive for post-stroke cognitive impairment after adjusting for age, education, and stroke severity compared to women. This study highlights that more large, prospective, and multicenter studies are needed to evaluate sex-specific changes after a stroke since sex differences exist in many aspects of stroke presentation and management.


Asunto(s)
Enfermedad de Alzheimer , Disfunción Cognitiva , Ataque Isquémico Transitorio , Accidente Cerebrovascular , Humanos , Femenino , Masculino , Estudios Prospectivos , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/epidemiología , Disfunción Cognitiva/psicología , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/diagnóstico , Enfermedad de Alzheimer/psicología
3.
N Engl J Med ; 389(7): 602-611, 2023 Aug 17.
Artículo en Inglés | MEDLINE | ID: mdl-37466280

RESUMEN

BACKGROUND: Findings from observational studies suggest that dietary patterns may offer protective benefits against cognitive decline, but data from clinical trials are limited. The Mediterranean-DASH Intervention for Neurodegenerative Delay, known as the MIND diet, is a hybrid of the Mediterranean diet and the DASH (Dietary Approaches to Stop Hypertension) diet, with modifications to include foods that have been putatively associated with a decreased risk of dementia. METHODS: We performed a two-site, randomized, controlled trial involving older adults without cognitive impairment but with a family history of dementia, a body-mass index (the weight in kilograms divided by the square of the height in meters) greater than 25, and a suboptimal diet, as determined by means of a 14-item questionnaire, to test the cognitive effects of the MIND diet with mild caloric restriction as compared with a control diet with mild caloric restriction. We assigned the participants in a 1:1 ratio to follow the intervention or the control diet for 3 years. All the participants received counseling regarding adherence to their assigned diet plus support to promote weight loss. The primary end point was the change from baseline in a global cognition score and four cognitive domain scores, all of which were derived from a 12-test battery. The raw scores from each test were converted to z scores, which were averaged across all tests to create the global cognition score and across component tests to create the four domain scores; higher scores indicate better cognitive performance. The secondary outcome was the change from baseline in magnetic resonance imaging (MRI)-derived measures of brain characteristics in a nonrandom sample of participants. RESULTS: A total of 1929 persons underwent screening, and 604 were enrolled; 301 were assigned to the MIND-diet group and 303 to the control-diet group. The trial was completed by 93.4% of the participants. From baseline to year 3, improvements in global cognition scores were observed in both groups, with increases of 0.205 standardized units in the MIND-diet group and 0.170 standardized units in the control-diet group (mean difference, 0.035 standardized units; 95% confidence interval, -0.022 to 0.092; P = 0.23). Changes in white-matter hyperintensities, hippocampal volumes, and total gray- and white-matter volumes on MRI were similar in the two groups. CONCLUSIONS: Among cognitively unimpaired participants with a family history of dementia, changes in cognition and brain MRI outcomes from baseline to year 3 did not differ significantly between those who followed the MIND diet and those who followed the control diet with mild caloric restriction. (Funded by the National Institute on Aging; ClinicalTrials.gov number, NCT02817074.).


Asunto(s)
Disfunción Cognitiva , Demencia , Dieta Mediterránea , Anciano , Anciano de 80 o más Años , Humanos , Encéfalo/diagnóstico por imagen , Cognición , Disfunción Cognitiva/prevención & control , Demencia/prevención & control , Dieta Hiposódica , Restricción Calórica
5.
Neurol Clin ; 41(2): 343-358, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-37030962

RESUMEN

Reviewing the research presented in this article, it is evident that from an epidemiological perspective, it is important to evaluate the extent to which findings of sex and gender differences in Alzheimer's dementia (AD) are due to differences in longevity, survival bias, and comorbidities. Medical, genetic, psychosocial, and behavioral factors, in addition to hormonal factors, can differentially affect the risk and progression of AD in women versus men. Further, evaluation of sex differences in AD progression and the trajectory of change in cognitive function, neuroimaging, cerebrospinal fluid (CSF), and blood-based biomarkers of AD is needed. Finally, identifying sex differences in AD biomarkers and change across the lifespan is critical for the planning of prevention trials to reduce the risk of developing AD.


Asunto(s)
Enfermedad de Alzheimer , Femenino , Humanos , Masculino , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/epidemiología , Factores Sexuales , Caracteres Sexuales , Progresión de la Enfermedad , Biomarcadores , Proteínas tau
6.
Neurology ; 100(22): e2259-e2268, 2023 05 30.
Artículo en Inglés | MEDLINE | ID: mdl-36889921

RESUMEN

BACKGROUND AND OBJECTIVES: Diet may reduce Alzheimer dementia risk and slow cognitive decline, but the understanding of the relevant neuropathologic mechanisms remains limited. The association of dietary patterns with Alzheimer disease (AD) pathology has been suggested using neuroimaging biomarkers. This study examined the association of Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) and Mediterranean dietary patterns with ß-amyloid load, phosphorylated tau tangles, and global AD pathology in postmortem brain tissue of older adults. METHODS: Autopsied participants of the Rush Memory and Aging Project with complete dietary information (collected through a validated food frequency questionnaire) and AD pathology data (ß-amyloid load, phosphorylated tau tangles, and global AD pathology [summarized neurofibrillary tangles and neuritic and diffuse plaques]) were included in this study. Linear regression models controlled for age at death, sex, education, APOE-ε4 status, and total calories were used to investigate the dietary patterns (MIND and Mediterranean diets) and dietary components associated with AD pathology. Further effect modification was tested for APOE-ε4 status and sex. RESULTS: Among our study participants (N = 581, age at death: 91.0 ± 6.3 years; mean age at first dietary assessment: 84.2 ± 5.8 years; 73% female; 6.8 ± 3.9 years of follow-up), dietary patterns were associated with lower global AD pathology (MIND: ß = -0.022, p = 0.034, standardized ß = -2.0; Mediterranean: ß = -0.007, p = 0.039, standardized ß = -2.3) and specifically less ß-amyloid load (MIND: ß = -0.068, p = 0.050, standardized ß = -2.0; Mediterranean: ß = -0.040, p = 0.004, standardized ß = -2.9). The findings persisted when further adjusted for physical activity, smoking, and vascular disease burden. The associations were also retained when participants with mild cognitive impairment or dementia at the baseline dietary assessment were excluded. Those in the highest tertile of green leafy vegetables intake had less global AD pathology when compared with those in the lowest tertile (tertile 3 vs tertile 1: ß = -0.115, p = 0.0038). DISCUSSION: The MIND and Mediterranean diets are associated with less postmortem AD pathology, primarily ß-amyloid load. Among dietary components, higher green leafy vegetable intake was associated with less AD pathology.


Asunto(s)
Enfermedad de Alzheimer , Disfunción Cognitiva , Dieta Mediterránea , Humanos , Femenino , Anciano , Anciano de 80 o más Años , Masculino , Enfermedad de Alzheimer/patología , Péptidos beta-Amiloides , Apolipoproteínas E
7.
Eur J Epidemiol ; 38(4): 427-434, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36867286

RESUMEN

Neurofilament light chain (NfL), a neuron-specific protein, has been related to several neurodegenerative diseases. In addition, elevated levels of NfL have also been observed in patients admitted to the hospital for stroke, suggesting that NfL as a biomarker may extend well beyond neurodegenerative diseases. Therefore, using data from the Chicago Health and Aging Project (CHAP), a population-based cohort study, we prospectively investigated the association of serum NfL levels with incident stroke and brain infarcts. During a follow-up of 3603 person-years, 133 (16.3%) individuals developed incident stroke, including ischemic and hemorrhagic. The HR (95%CI) of incident stroke was 1.28 (95%CI 1.10-1.50) per 1 standard deviation (SD) increase of log10 NfL serum levels. Compared to participants in the first tertile of NfL (i.e., lower levels), the risk of stroke was 1.68 times higher (95%CI 1.07-2.65) in those in the second tertile and 2.35 times higher (95%CI 1.45-3.81) in those in the third tertile of NfL. NfL levels were also positively associated with brain infarcts; 1-SD in log10 NfL levels was associated with 1.32 (95%CI 1.06-1.66) higher odds of one or more brain infarcts. These results suggest that NfL may serve as a biomarker of stroke in older adults.


Asunto(s)
Enfermedades Neurodegenerativas , Accidente Cerebrovascular , Anciano , Humanos , Biomarcadores , Infarto Encefálico/epidemiología , Infarto Encefálico/metabolismo , Estudios de Cohortes , Filamentos Intermedios/metabolismo , Enfermedades Neurodegenerativas/epidemiología , Enfermedades Neurodegenerativas/metabolismo , Estudios Prospectivos , Accidente Cerebrovascular/epidemiología , Incidencia
8.
Alzheimers Dement ; 19(8): 3555-3562, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-36825796

RESUMEN

INTRODUCTION: Intervention of Alzheimer's dementia hinges on early diagnosis and advanced planning. This work utilizes the cognitive clock, a novel indicator of brain health, to develop a dementia prediction model that can be easily applied in broad settings. METHODS: Data came from over 3000 community-dwelling older adults. Cognitive age was estimated by aligning Mini-Mental State Examination (MMSE) scores to a clock that represents the typical cognitive aging profile. We identified a mean cognitive age at Alzheimer's dementia onset and predicted the corresponding chronological age at person-specific level. RESULTS: The mean chronological age at baseline was 78 years. A total of 881 (28%) participants developed Alzheimer's dementia. The mean cognitive age at onset was 91 years. The predicted chronological age at onset had a mean (standard deviation) of 87.6 (6.7) years. The model's prediction accuracy was supported by multiple testing statistics. DISCUSSION: Our model offers an easy-to-use tool for predicting person-specific age at Alzheimer's dementia onset.


Asunto(s)
Enfermedad de Alzheimer , Disfunción Cognitiva , Humanos , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/diagnóstico , Encéfalo , Vida Independiente , Cognición
9.
Alzheimers Dement ; 19(7): 3087-3097, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-36708229

RESUMEN

OBJECTIVE: Investigate associations between the LIfestyle for BRAin Health (LIBRA) risk score with odds of mild cognitive impairment (MCI) diagnosis and cognitive function, incorporating concussion history. METHODS: Former National Football League (NFL) players (N = 1050; mean age = 64.8 ± 9.0-years) completed initial testing for integration of concussion history into LIBRA scores (i.e., modified-LIBRA) and completed the Brief Test of Adult Cognition by Telephone (BTACT). Modified-LIBRA score (including concussion history) associations with odds of MCI and cognitive dysfunction were assessed via logistic and linear regression. RESULTS: The highest quartile LIBRA scores were six times more likely to have a diagnosis of MCI compared to the lowest quartile (OR = 6.27[3.61, 10.91], p < 0.001). Modified-LIBRA scores significantly improved model fit for odds of MCI above original LIBRA scores (χ2 (1) = 7.76, p = 0.005) and accounted for a greater fraction of variance in executive function (ΔR2  = 0.02, p = 0.003) and episodic memory (ΔR2  = 0.02, p = 0.002). CONCLUSIONS: Modified-LIBRA score, incorporating concussion history, may help monitoring risk status in former contact sport athletes, by targeting modifiable, lifestyle-related risk factors.


Asunto(s)
Conmoción Encefálica , Fútbol Americano , Adulto , Humanos , Anciano , Persona de Mediana Edad , Encéfalo , Cognición , Conmoción Encefálica/diagnóstico , Estilo de Vida , Factores de Riesgo
10.
J Alzheimers Dis ; 91(3): 961-976, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36530086

RESUMEN

BACKGROUND: Biological biomarkers yielded from positron emission tomography (PET) brain scans serve as a pathway to understanding Alzheimer's disease pathology. PET brain scan data remain limited for populations traditionally under-included in aging research. OBJECTIVE: The purpose of this qualitative study was to examine participant-identified barriers to PET brain scan consent and characterize participant-informed elements of educational materials needed to facilitate PET brain scan participation among older Black and Latino adults. METHODS: Participants (N = 31) were older adults (mean age = 71 years) who self-identified as either non-Latino Black (n = 15) or Latino (n = 16). Each participant took part in a one-time, in-depth individual interview. Researchers analyzed data guided by a Grounded Theory Approach with both Open Coding and Constant Comparative Coding. RESULTS: Four overarching themes emerged across all participants: 1) knowledge limitations; 2) requirements for consent; 3) motivators for participation; and 4) social networks. Within the four themes, there were differences based on participant ethnoracial group. For example, for Theme Three, older Black adults indicated that they would expect compensation for PET brain scan participation. Conversely, older Latinos stated that they would appreciate, but not anticipate, a financial incentive. All participants stressed the importance of written educational materials with subsequent verbal discussions with studystaff. CONCLUSION: Findings inform the development and implementation of scientifically-relevant and culturally-cognizant engagement approaches, educational materials, and recruitment strategies to increase PET brain scan participation by diverse older adults.


Asunto(s)
Encéfalo , Tomografía de Emisión de Positrones , Humanos , Anciano , Encéfalo/diagnóstico por imagen , Investigación Cualitativa , Motivación
11.
Neurology ; 100(8): e874-e883, 2023 02 21.
Artículo en Inglés | MEDLINE | ID: mdl-36446595

RESUMEN

BACKGROUND AND OBJECTIVES: Recent studies suggest the utility of blood biomarkers in detecting changes in neurodegenerative disorders. The objective of our research was to test the hypothesis that the longitudinal changes in total tau (t-tau), neurofilament light chain (Nf-L), and glial fibrillary acidic protein (GFAP) are associated with structural MRI and the development of clinical Alzheimer disease (AD) and cognitive decline. METHODS: Data came from a population-based sample with serum concentrations of t-tau, Nf-L, and GFAP and cognitive characteristics measured over 17 years. The inclusion criteria for this investigation were based on participants with blood samples, cognitive function testing, and clinical diagnosis for AD. The longitudinal changes in the serum biomarkers were examined using linear mixed models for log10-transformed concentrations. RESULTS: In 1,327 participants (60% Black participants and 60% women, the concentration of t-tau increased annually by 4.8% (95% CI = 4.0-5.6) and Nf-L by 5.9% (95% CI = 5.4-6.4). The longitudinal change in GFAP was higher among Black participants than among White participants (4.4% vs 3.5% per year, p = 0.028). Baseline MRI characteristics were associated with the longitudinal changes in serum biomarkers of clinical AD. Specifically, a higher baseline third ventricular volume was associated with a higher rate of increase in the concentration of t-tau, and white matter hyperintensities predicted a higher rate of increase in Nf-L. The rate of change in concentrations of t-tau, Nf-L, and GFAP was significantly higher among those who developed clinical AD than in those with no cognitive impairment. For each standard deviation unit decline in global cognition, longitudinal change in t-tau increased by 81% (95% CI = 76-86), Nf-L by 113% (95% CI = 105-120), and GFAP by 66% (95% CI = 62-70). DISCUSSION: Blood biomarkers showed significant longitudinal changes corresponding to cognitive decline, clinical AD, and structural MRI characteristics. Our findings show that longitudinal changes in serum biomarkers were associated with several cognitive endophenotypes. CLASSIFICATION OF EVIDENCE: The study found Class II evidence that longitudinal changes in serum t-tau, Nf-L, and GFAP were associated with cognitive decline and the development of clinical AD in people older than 65 years.


Asunto(s)
Enfermedad de Alzheimer , Disfunción Cognitiva , Humanos , Femenino , Masculino , Enfermedad de Alzheimer/complicaciones , Proteínas tau , Biomarcadores , Cognición , Imagen por Resonancia Magnética , Disfunción Cognitiva/psicología , Péptidos beta-Amiloides
12.
J Int Neuropsychol Soc ; 29(6): 582-593, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-36039970

RESUMEN

OBJECTIVES: Subjective cognitive difficulties (SCDs) are associated with factors commonly reported in older adults and former contact sport athletes, regardless of objective cognitive decline. We investigated the relative contribution of these factors to SCD in former National Football League (NFL)-players with and without a diagnosis of mild cognitive impairment (MCI). METHODS: Former NFL players (n = 907) aged ≥ 50 years (mean = 64.7 ± 8.9), with (n = 165) and without (n = 742) a diagnosis of MCI completed health questionnaires. Multivariable regression and dominance analyses determined the relative importance of SCD factors on SCD: 1) depression, 2) anxiety, 3) sleep disturbance, 4) pain interference, 5) ability to participate in social roles and activities, 6) stress-related events, 7) fatigue, 8) concussion history, and 9) education. SCD outcomes included Neuro-QoL Emotional-Behavioral Dyscontrol and the PROMIS Cognitive Function. Fisher's z-transformation compared comorbid contributing factors to SCD across MCI and non-MCI groups. RESULTS: Complete dominance of anxiety was established over most comorbid factors across the MCI and non-MCI groups. Fatigue also exhibited complete dominance over most comorbid factors, though its influence in the MCI group was less robust (general dominance). Average contributions to variance accounted for by comorbid factors to ratings of SCD across MCI and non-MCI groups did not statistically differ (Z-statistics <1.96, ps>.05). CONCLUSIONS: Anxiety and fatigue are the most robust factors associated with SCD in former professional football players across various combinations of clinical presentations (different combinations of comorbid factors), regardless of documented cognitive impairment. Self-reported deficits may be less reliable in detecting objective impairment in the presence of these factors, with multidimensional assessment being ideal.


Asunto(s)
Conmoción Encefálica , Disfunción Cognitiva , Fútbol Americano , Humanos , Anciano , Calidad de Vida , Disfunción Cognitiva/psicología , Conmoción Encefálica/complicaciones , Conmoción Encefálica/epidemiología , Conmoción Encefálica/diagnóstico , Cognición
13.
Am Heart J Plus ; 26: 100266, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38510193

RESUMEN

Study objective: We sought to evaluate the sex-based disparities and comparative in-hospital outcomes of principal AF hospitalizations in patients with and without dementia, which have not been well-studied. Design: This is a non-interventional retrospective cohort study. Setting and participants: We identified principal hospitalizations of AF in the National Inpatient Sample in adults (≥18 years old) between January 2016 and December 2019. Main outcome measure: In-hospital mortality. Results: Of 378,230 hospitalized patients with AF, 49.2 % (n = 186,039) were females and 6.1 % (n = 22,904) had dementia. The mean age (SD) was 71 (13) years. Patients with dementia had higher odds of in-hospital mortality {adjusted odds ratio (aOR): 1.48, 95 % confidence interval (CI): 1.34, 1.64, p < 0.001} and nontraumatic intracerebral hemorrhage (aOR: 1.60, 95 % CI: 1.04, 2.47, p = 0.032), but they had lower odds of catheter ablation (0.39, 95 % CI: 0.35, 0.43, p < 0.001) and electrical cardioversion (aOR: 0.33, 95 % CI: 0.31, 0.35, p < 0.001). In patients with AF and dementia, compared to males, females had similar in-hospital mortality (aOR: 1.00, 95 % CI: 0.93, 1.07, p = 0.960), fewer gastrointestinal bleeds (aOR: 0.92, 95 % CI: 0.85, 0.99, p = 0.033), lower odds of getting catheter ablation (aOR: 0.79, 95 % CI: 0.76, 0.81, p < 0.001), and less likelihood of getting electrical cardioversion (aOR: 0.78, 95 % CI: 0.76, 0.79, p < 0.001). Conclusions: Patients with AF and dementia have higher mortality and a lower likelihood of getting catheter ablation and electrical cardioversion.

14.
Ann Neurol ; 92(5): 729-744, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36151869

RESUMEN

OBJECTIVE: To determine the characteristics of participants with amyloid-related imaging abnormalities (ARIA) in a trial of gantenerumab or solanezumab in dominantly inherited Alzheimer disease (DIAD). METHODS: 142 DIAD mutation carriers received either gantenerumab SC (n = 52), solanezumab IV (n = 50), or placebo (n = 40). Participants underwent assessments with the Clinical Dementia Rating® (CDR®), neuropsychological testing, CSF biomarkers, ß-amyloid positron emission tomography (PET), and magnetic resonance imaging (MRI) to monitor ARIA. Cross-sectional and longitudinal analyses evaluated potential ARIA-related risk factors. RESULTS: Eleven participants developed ARIA-E, including 3 with mild symptoms. No ARIA-E was reported under solanezumab while gantenerumab was associated with ARIA-E compared to placebo (odds ratio [OR] = 9.1, confidence interval [CI][1.2, 412.3]; p = 0.021). Under gantenerumab, APOE-ɛ4 carriers were more likely to develop ARIA-E (OR = 5.0, CI[1.0, 30.4]; p = 0.055), as were individuals with microhemorrhage at baseline (OR = 13.7, CI[1.2, 163.2]; p = 0.039). No ARIA-E was observed at the initial 225 mg/month gantenerumab dose, and most cases were observed at doses >675 mg. At first ARIA-E occurrence, all ARIA-E participants were amyloid-PET+, 60% were CDR >0, 60% were past their estimated year to symptom onset, and 60% had also incident ARIA-H. Most ARIA-E radiologically resolved after dose adjustment and developing ARIA-E did not significantly increase odds of trial discontinuation. ARIA-E was more frequently observed in the occipital lobe (90%). ARIA-E severity was associated with age at time of ARIA-E. INTERPRETATION: In DIAD, solanezumab was not associated with ARIA. Gantenerumab dose over 225 mg increased ARIA-E risk, with additional risk for individuals APOE-ɛ4(+) or with microhemorrhage. ARIA-E was reversible on MRI in most cases, generally asymptomatic, without additional risk for trial discontinuation. ANN NEUROL 2022;92:729-744.


Asunto(s)
Enfermedad de Alzheimer , Humanos , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/genética , Estudios Transversales , Péptidos beta-Amiloides , Amiloide , Biomarcadores , Apolipoproteínas E
15.
J Alzheimers Dis ; 89(2): 745-754, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35938251

RESUMEN

BACKGROUND: Patients with stroke are at a higher risk of cognitive impairment and Alzheimer's disease dementia. OBJECTIVE: To quantify the role of lifestyle pre-stroke, post-stroke, and changes in lifestyle before and after stroke with cognitive decline in community-dwelling stroke survivors. METHODS: Utilizing data from the Chicago Health and Aging Project, a population-based cohort study, we studied 1,078 individuals with stroke (662 incident and 416 prevalent) who underwent cognitive testing during the study period. A healthy lifestyle score was defined by scoring four behaviors: non-smoking, exercising, being cognitively active, and having a high-quality diet. The global cognitive score was derived from a comprehensive battery of 4 standardized tests. RESULTS: The mean age at incident stroke was 78.2 years, and 60.1% were women. A healthy lifestyle pre-incident stroke was associated with a slower rate of cognitive decline after stroke. Participants with 3-4 healthy lifestyle factors pre-incident stroke had a slower cognitive decline after stroke by 0.046 units/year (95% CI 0.010, 0.083), or 47.7% slower, than participants with 0-1 healthy lifestyle factor. Lifestyle score post-prevalent stroke was not associated with cognitive decline. Changes in lifestyle behaviors from pre- to post-incident stroke were related to cognitive decline after stroke. Individuals who deteriorated their lifestyle quality after stroke had a faster cognitive decline by 0.051 units/year (ß -0.051, 95% CI -0.090, -0.012) than participants with no change in lifestyle score. CONCLUSION: A healthy lifestyle pre-stroke was associated with a slower rate of cognitive decline in stroke survivors, highlighting the importance of primary prevention. After the stroke, changes in lifestyle behaviors may influence the cognitive abilities of older adults as they age.


Asunto(s)
Disfunción Cognitiva , Accidente Cerebrovascular , Anciano , Cognición , Disfunción Cognitiva/complicaciones , Disfunción Cognitiva/etiología , Estudios de Cohortes , Femenino , Humanos , Vida Independiente , Estilo de Vida , Masculino , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/psicología , Sobrevivientes
16.
J Alzheimers Dis ; 90(3): 953-962, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35938255

RESUMEN

The brain changes of Alzheimer's disease and other degenerative dementias begin long before cognitive dysfunction develops, and in people with subtle cognitive complaints, clinicians often struggle to predict who will develop dementia. The public increasingly sees benefits to accessing dementia risk evidence (DRE) such as biomarkers, predictive algorithms, and genetic information, particularly as this information moves from research to demonstrated usefulness in guiding diagnosis and clinical management. For example, the knowledge that one has high levels of amyloid in the brain may lead one to seek amyloid reducing medications, plan for disability, or engage in health promoting behaviors to fight cognitive decline. Researchers often hesitate to share DRE data, either because they are insufficiently validated or reliable for use in individuals, or there are concerns about assuring responsible use and ensuring adequate understanding of potential problems when one's biomarker status is known. Concerns include warning people receiving DRE about situations in which they might be compelled to disclose their risk status potentially leading to discrimination or stigma. The Advisory Group on Risk Evidence Education for Dementia (AGREEDementia) welcomes all concerned with how best to share and use DRE. Supporting understanding in clinicians, stakeholders, and people with or at risk for dementia and clearly delineating risks, benefits, and gaps in knowledge is vital. This brief overview describes elements that made this group effective as a model for other health conditions where there is interest in unfettered collaboration to discuss diagnostic uncertainty and the appropriate use and communication of health-related risk information.


Asunto(s)
Enfermedad de Alzheimer , Disfunción Cognitiva , Demencia , Humanos , Demencia/diagnóstico , Enfermedad de Alzheimer/diagnóstico , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/terapia , Amiloide , Biomarcadores
17.
J Am Geriatr Soc ; 70(11): 3185-3194, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-35920078

RESUMEN

BACKGROUND: Over 5 million older Americans are victims of financial exploitation, schemes, and/or scams per year. Such victimization is associated with increased hospitalizations, admittance to skilled nursing facilities, and lower 5-year all-cause mortality survival rates. Despite this, associations with medical comorbidities like elevated blood pressure (BP) have not been examined. METHODS: We investigated the association of self-reported fraud victimization (presence/absence) with objectively measured BP metrics leveraging cross-sectional and longitudinal data from over 1200 non-demented adults (75% female; age ~81 years) from the Rush Memory and Aging Project. We first examined cross-sectional associations between baseline fraud victimization and BP, then used longitudinal data to test the hypothesis that fraud victimization is associated with increases in BP after incident fraud. During up to 11 years of annual observation, participants were queried for fraud victimization and underwent serial BP measurements to calculate per visit averages of systolic and diastolic BP, mean arterial pressure (MAP), and pulse pressure. RESULTS: Cross-sectional analyses established that fraud victimization at baseline was associated with higher BP values. Next, using longitudinal changepoint analyses, we showed that fraud victimization was associated with elevations in BP among men but not women. Specifically, men who reported incident fraud exhibited increases in all BP metrics post-fraud. CONCLUSION: Results suggest an important link between fraud victimization and BP, particularly among men. Older men showed significant elevations in BP after incident fraud that, compounded over time, may portend other adverse health outcomes.


Asunto(s)
Víctimas de Crimen , Hipertensión , Femenino , Humanos , Masculino , Anciano , Anciano de 80 o más Años , Presión Sanguínea/fisiología , Autoinforme , Caracteres Sexuales , Estudios Transversales , Hipertensión/complicaciones , Fraude
18.
J Alzheimers Dis ; 90(3): 1001-1009, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35723099

RESUMEN

BACKGROUND: Study participants, patients, and care partners are key stakeholders in research and have asked for greater inclusion in the dissemination of scientific learning. However, the participation of general audiences in scientific conferences dedicated to Alzheimer's disease and Alzheimer's disease related dementias (AD/ADRD) is not widely supported or studied. OBJECTIVE: Our objectives were to evaluate the interest, level of engagement, and impact of including general audiences in a virtual dementia conference. METHODS: A diverse group of lay participants, identified via community-based health advocacy groups and research centers, were invited to attend the 2021 Alzheimer's Association International Conference (AAIC), with optional small-group discussions. Participants received complimentary access to all scientific sessions and were supported via navigation tips, recommended sessions, and a glossary of frequently used terms and acronyms. RESULTS: Lay participants demonstrated a high level of engagement, even among those that were research-naïve, attending virtual sessions for an average of 11.7 hours across the five days and recommending a variety of sessions to each other on topics extending from prevention of dementia to new therapies and care. Most participants said they would attend the conference again and rated the quality of interaction as high, while requesting more opportunities to engage directly with researchers. CONCLUSION: General audiences, in particular research participants, are advocating for greater participation in scientific conferences. This program can serve as a model to accomplish inclusion; thereby acknowledging their invaluable contribution to science.


Asunto(s)
Enfermedad de Alzheimer , Humanos , Enfermedad de Alzheimer/terapia
19.
J Alzheimers Dis ; 88(2): 653-661, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35694918

RESUMEN

BACKGROUND: An anthocyanidin, pelargonidin, primarily found in berries, has antioxidant and anti-inflammatory properties, and is associated with better cognition and reduced Alzheimer's dementia risk. OBJECTIVE: This study investigated if pelargonidin or berry intake is associated with Alzheimer's disease (AD) neuropathology in human brains. METHODS: The study was conducted among 575 deceased participants (age at death = 91.3±6.1 years; 70% females) of the Rush Memory and Aging Project, with dietary data (assessed using a food frequency questionnaire) and neuropathological evaluations. Calorie-adjusted pelargonidin intake was modeled in quartiles and berry intake as continuous (servings/week). Mean amyloid-beta load and phosphorylated tau neuronal neurofibrillary tangle density across multiple cortical regions were assessed using immunohistochemistry. Global AD pathology burden, a quantitative summary score of neurofibrillary tangles, and diffuse and neuritic plaques using Bielschowsky silver stains in multiple brain regions, was also assessed. RESULTS: In a linear regression model adjusted for age at death, sex, education, APOE ɛ4 status, vitamin E, and vitamin C, participants in the highest quartile of pelargonidin intake when compared to those in the lowest quartile, had less amyloid-ß load (ß (SE) = -0.293 (0.14), p = 0.038), and fewer phosphorylated tau tangles (ß (SE) = -0.310, p = 0.051). Among APOE ɛ4 non-carriers, higher strawberry (ß (SE) = -0.227 (0.11), p = 0.037) and pelargonidin (Q4 versus Q1: ß (SE) = -0.401 (0.16), p = 0.011; p trend = 0.010) intake was associated with less phosphorylated tau tangles, no association was observed in APOE ɛ4 carriers. Berry intake was not associated with AD pathology. However, excluding participants with dementia or mild cognitive impairment at baseline, strawberry (p = 0.004) and pelargonidin (ptrend = 0.007) intake were associated with fewer phosphorylated tau tangles. CONCLUSION: Higher intake of pelargonidin, a bioactive present in strawberries, is associated with less AD neuropathology, primarily phosphorylated tau tangles.


Asunto(s)
Enfermedad de Alzheimer , Anciano de 80 o más Años , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/patología , Péptidos beta-Amiloides/metabolismo , Antocianinas , Apolipoproteínas E , Encéfalo/patología , Femenino , Frutas/metabolismo , Humanos , Masculino , Ovillos Neurofibrilares/patología , Proteínas tau/metabolismo
20.
J Genet Couns ; 31(4): 989-997, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35460578

RESUMEN

As more is understood about the hereditary nature of disease risk, the utility of genetic testing within cardiovascular medicine is increasingly being explored. Although testing may afford more personalized risk stratification, there is a paucity of information regarding patient knowledge, attitudes, and beliefs toward genetic testing among cardiology patients. Participants (n = 530) recruited primarily from a cardiology clinic filled out a 41-item written questionnaire assessing knowledge, beliefs, and attitudes toward genetic testing, motivators and detractors for considering genetic testing, and perceived likelihood for behavior change after hypothetical genetic testing risk stratification. Path analysis was used to test the hypothetical models predicting the likelihood of getting a genetic test and making behavior changes following genetic testing. The patient population was late-middle-aged (59.0 ± 14.5 years), majority women (61.5%), and about half reported having a bachelor's degree. 58.1% of participants self-identified as White, 25.7% as African American or Black, 6.8% as Spanish, Latino, or Hispanic, 3.0% as Asian or Pacific Islander, and 0.5% as Native American. Gender (being a woman) and more years of education were related to greater knowledge about genetic testing. Racial identity and years of education were related to beliefs about genetic testing. Beliefs, but not knowledge, were related to more positive attitudes and a higher likelihood of pursuing genetic testing. Positive attitudes were related to greater perceived personal control (PPC). Furthermore, attitudes and PPC were related to higher likelihood of lifestyle change after genetic testing. These results highlight the need to integrate the experiences of racialized communities into education/counseling efforts. Most educational counseling efforts lack a nuanced discussion of social determinants of health or beliefs. In addition to factual information, educational counseling must also address people's beliefs, concerns, and the intersecting experiences and identities, which shape patients' relationships with the evolving landscape of healthcare and personalized medicine.


Asunto(s)
Actitud , Cardiología , Negro o Afroamericano , Instituciones de Atención Ambulatoria , Femenino , Pruebas Genéticas , Conocimientos, Actitudes y Práctica en Salud , Humanos , Persona de Mediana Edad , Encuestas y Cuestionarios
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