Authors: Harvey, Danielle J. | Beckett, Laurel A. | Mungas, Dan M.
Article Type: Research Article
Abstract: Longitudinal studies of Alzheimer's disease provide information about cognitive decline and predictors of this decline. However, overall cognitive function is comprised of many underlying processes, each of which may respond differently over time and may be affected by different predictors. In addition to studying how these processes decline independently, one might also be interested in how the processes decline together. Multivariate growth models, an extension and modification of random effects models, provide a means of dealing with these issues and enable assessing the association between the processes of interest. This technique allows for separate random effects and predictors for each …process in the same model, thereby providing simultaneous estimates of the model parameters and variability for each process. We can then determine if factors associated with decline in one process are also associated with decline in another process and the extent to which the processes differ. We provide data that include information on two underlying processes of cognitive function, namely memory and executive function, to illustrate this methodology. Show more
DOI: 10.3233/JAD-2003-5502
Citation: Journal of Alzheimer's Disease, vol. 5, no. 5, pp. 357-365, 2003
Authors: DeCarli, Charles | Villeneuve, Sylvia | Maillard, Pauline | Harvey, Danielle | Singh, Baljeet | Carmichael, Owen | Fletcher, Evan | Olichney, John | Farias, Sarah | Jagust, William | Reed, Bruce | Mungas, Dan
Article Type: Research Article
Abstract: Background/Objective: To determine the impact of vascular burden on rates of decline in episodic memory and executive function. We hypothesize that greater vascular burden will have an additive negative impact on cognition after accounting for baseline cognitive impairment, positron emission tomography (PET) amyloid burden, and magnetic resonance imaging (MRI) measures. Methods: Individuals were followed an average of 5 years with serial cognitive assessments. Predictor variables include vascular burden score (VBS), quantitative brain MRI assessment, and amyloid imaging. Subjects consisted of 65 individuals, 53% of whom were male, aged 73.2±7.2 years on average with an average of 15.5±3.3 years of educational …achievement. Results: Baseline cognitive impairment was significantly associated poorer episodic memory (p < 0.0001), smaller hippocampal volume (p < 0.0001), smaller brain volume (p = 0.0026), and greater global Pittsburg Imaging Compound B (PiB) index (p = 0.0008). Greater amyloid burden was associated with greater decline in episodic memory over time (β= –0.20±0.07, p < 0.005). VBS was significantly associated with the level of executive function performance (β= –0.14±0.05, p < 0.005) and there was a significant negative interaction between VBS, cognitive impairment, and PiB index (β= –0.065±0.03, p = 0.03). Conclusions: Our results find a significant influence of VBS independent of standard MRI measures and cerebral amyloid burden on executive function. In addition, VBS reduced the amount of cerebral amyloid burden needed to result in cognitive impairment. We conclude that the systemic effects of vascular disease as reflected by the VBS independently influence cognitive ability. Show more
Keywords: Alzheimer’s disease, cerebrovascular disorders, cognition, neuroimaging
DOI: 10.3233/JAD-180965
Citation: Journal of Alzheimer's Disease, vol. 68, no. 1, pp. 187-196, 2019
Authors: Casaletto, Kaitlin B. | Rentería, Miguel Arce | Pa, Judy | Tom, Sarah E. | Harrati, Amal | Armstrong, Nicole M. | Rajan, K. Bharat | Mungas, Dan | Walters, Samantha | Kramer, Joel | Zahodne, Laura B.
Article Type: Research Article
Abstract: Background: Active lifestyles are related to better cognitive aging outcomes, yet the unique role of different types of activity are unknown. Objective: To examine the independent contributions of physical (PA) versus cognitive (CA) leisure activities to brain and cognitive aging. Methods: Independent samples of non-demented older adults from University of California, San Francisco Hillblom Aging Network (UCSF; n = 344 typically aging) and University of California, Davis Diversity cohort (UCD; n = 485 normal to MCI) completed: 1) self-reported engagement in current PA and CA (UCSF: Physical Activity Scale for the Elderly and Cognitive Activity Scale; UCD: Life Experiences Assessment Form); 2) …neuropsychological batteries; and 3) neuroimaging total gray matter volume, white matter hyperintensities, and/or global fractional anisotropy. PA and CA were simultaneously entered into multivariable linear regression models, adjusting for demographic characteristics and functional impairment severity. Results: Brain outcomes : In UCSF, only PA was positively associated with gray matter volume and attenuated the relationship between age and fractional anisotropy. In UCD, only CA was associated with less white matter hyperintensities and attenuated the relationship between age and gray matter volume. Cognitive outcomes : In both cohorts, greater CA, but not PA, related to better cognition, independent of age and brain structure. In UCSF, CA attenuated the relationship between fractional anisotropy and cognition. In UCD, PA attenuated the association between white matter hyperintensities and cognition. Conclusions: Although their specificity was not easily teased apart, both PA and CA are clearly related to better brain and cognitive resilience markers across cohorts with differing educational, racial, and disease statuses. PA and CA may independently contribute to converging neuroprotective pathways for brain and cognitive aging. Show more
Keywords: Brain aging, cognitive aging, exercise, mental stimulation, reserve
DOI: 10.3233/JAD-191114
Citation: Journal of Alzheimer's Disease, vol. 74, no. 1, pp. 363-376, 2020
Authors: Filshtein, Teresa Jenica | Dugger, Brittany N. | Jin, Lee-Way | Olichney, John M. | Farias, Sarah T. | Carvajal-Carmona, Luis | Lott, Paul | Mungas, Dan | Reed, Bruce | Beckett, Laurel A. | DeCarli, Charles
Article Type: Research Article
Abstract: Our nation is becoming increasingly diverse; however, few autopsy studies examine multiple ethnoracial groups, especially Hispanics. We examined differences in neuropathological diagnoses of 423 deceased participants with dementia from three ethnoracial groups (35 Black, 28 Hispanic, and 360 non-Hispanic White) evaluated at the University of California Davis Alzheimer’s Disease Center. We used novel applications of bootstrap resampling and logistic regression standardization to project neuropathological diagnostic rates for non-Hispanic Whites to minority sample characteristics to improve inference of findings. Alzheimer’s disease (AD) without significant cerebrovascular disease (CVD) or other dementia-related pathologies (AD (non-mixed)) was present in 15 Black (43%), 4 Hispanic …(14%), and 156 (43%) non-Hispanic Whites. CVD sufficient to contribute to dementia was confirmed in 14 Black (40%), 15 Hispanic (54%), and 101 (28%) non-Hispanic White decedents. The observed CVD prevalence of 40% in Blacks exceeded the predicted 29% [95% CI: 22%-36%]. Despite being outside the 95% confidence interval, the difference between observed and predicted was not statistically significant after bootstrap testing. Conversely, for Hispanics, the observed proportion at 54% exceeded significantly the predicted prevalence of 24% from non-Hispanic Whites [95% CI: 16%-34%], avg. p = 0.008). An identical analysis using AD (non-mixed) as the outcome predicted AD (non-mixed) in Blacks averaging 41% [95% CI: 34%-48%], nearly equal to observed prevalence. For Hispanics, however, the observed proportion at 14%, was well below predictions (mean = 42%, 95% CI: 32%-53%], avg. p = 0.008). We conclude mixed diagnoses and CVD are more common in Hispanic and Black decedents than Non-Hispanic Whites with dementia in our cohort. The increased prevalence of vascular co-morbidity may be a potential opportunity to intervene more effectively in dementia treatment of those individuals. Show more
Keywords: Alzheimer’s disease, autopsy, brain, cognitive aging, cohort studies, dementia, minority groups, neuropathology, vascular
DOI: 10.3233/JAD-180992
Citation: Journal of Alzheimer's Disease, vol. 68, no. 1, pp. 145-158, 2019
Authors: Bettcher, Brianne M. | Ard, M. Colin | Reed, Bruce R. | Benitez, Andreana | Simmons, Amanda | Larson, Eric B. | Sonnen, Josh A. | Montine, Thomas J. | Li, Ge | Keene, C. Dirk | Crane, Paul K. | Mungas, Dan
Article Type: Research Article
Abstract: We characterized the relationship between late life cholesterol exposure and neuropathological outcomes in a community-based, older adult cohort. Adult Changes in Thought (ACT) is a cohort study that enrolls consenting, randomly selected, non-demented people aged ≥65 from a healthcare delivery system. We used late life HDL and total cholesterol lab values from Group Health computerized records, and calculated HDL and non-HDL levels. We evaluated neuropathological outcomes of Alzheimer’s disease, cerebral amyloid angiopathy, vascular brain injury, and Lewy body disease. Using linear mixed models with age and antilipemic medication as predictors, we obtained predicted cholesterol values at age 70 and 10 …years prior to death for individuals with available cholesterol data in 10-year exposure windows. We used logistic regression to determine whether predicted late life cholesterol levels were associated with neuropathological outcomes controlling for age at death, APOE genotype, sex, and their interactions with cholesterol levels. 525 decedents came to autopsy by 08/2014. Of these, plasma cholesterol concentration was available for 318 (age 70, model 1) and 396 (10 years prior to death, model 2) participants. We did not find associations between late life cholesterol and Alzheimer’s disease neuropathological changes, and there were no associations between cholesterol levels and amyloid angiopathy or vascular brain injury. We observed an association between predicted non-HDL cholesterol at age 70 and Lewy body disease. Our study suggests an association between late life non-HDL cholesterol exposure and Lewy body disease. We did not observe associations between late life cholesterol levels and Braak stage or CERAD score. Show more
Keywords: Alzheimer’s disease, epidemiology, Lewy body, lipids, neuropathology, vascular
DOI: 10.3233/JAD-161224
Citation: Journal of Alzheimer's Disease, vol. 59, no. 4, pp. 1307-1315, 2017
Authors: Huie, Emily Z. | Escudero, Anthony | Saito, Naomi | Harvey, Danielle | Nguyen, My-Le | Lucot, Katherine L. | LaGrande, Jayne | Mungas, Dan | DeCarli, Charles | Lamar, Melissa | Schneider, Julie A. | Kapasi, Alifiya | Rissman, Robert A. | Teich, Andrew F. | Dugger, Brittany N.
Article Type: Research Article
Abstract: Background: Transactive Response DNA Binding Protein 43 kDa (TDP-43) pathology is frequently found in cases with Alzheimer’s disease (AD). TDP-43 pathology is associated with hippocampal atrophy and greater AD severity denoted by cognition and clinical representation. Current TDP-43 pathology studies are predominantly based on non-Hispanic White cohorts. Objective: We sought to evaluate the presence of TDP-43 pathology across ethnoracial groups utilizing the National Alzheimer’s Coordinating Center; a database containing data from over 29 institutions across the United States. Cases (N = 1135: Hispanics/Latinos = 29, African Americans/Black Americans = 51, Asians/Asian Americans = 10, American Indians/Alaskan Natives = 2, non-Hispanic …White = 1043) with intermediate/high AD having data on TDP-43 pathology in the amygdala, hippocampus, entorhinal cortex, and neocortex were included. Methods: TDP-43 pathology frequency in each neuroanatomic region among ethnoracial groups were compared using generalized linear mixed effects models with center as a random effect adjusting for age at death, education, and gender. Results: Although groups were imbalanced, there was no significant difference across ethnoracial groups based on TDP-43 pathology (p = 0.84). With respect to neuroanatomical regions evaluated, there were no significant differences across ethnoracial groups (p -values > 0.06). There were also no significant differences for age at death and gender ratios across ethnoracial groups based on TDP-43 pathology. Although not statistically significant, TDP-43 pathology was present less often in Hispanic/Latinos (34%) when compared to non-Hispanic Whites (46%). Conclusion: While this is a preliminary evaluation, it highlights the need for diverse cohorts and on TDP-43 pathology research across ethnoracial groups. This is the first study to our knowledge having a focus on the neuroanatomical distribution of TDP-43 deposits in Hispanic/Latino decedents with AD. Show more
Keywords: African American, Alzheimer’s disease, Asian, brain, cohort studies, Hispanic, Latino, minoritized groups, neuropathology
DOI: 10.3233/JAD-220558
Citation: Journal of Alzheimer's Disease, vol. 91, no. 4, pp. 1291-1301, 2023