Background
As part of the Research in African American Alzheimer Disease Initiative (REAAADI) and Late‐Onset AD Family Study (LOAD), genotyping array and whole genome sequencing (WGS) data were ...generated for 51 families (160 affected and 318 unaffected). Multipoint linkage analyses identified a peak LOD score on chr5q35 (HLOD=3.20). Additionally, a suggestive locus flanking the 1‐LOD score was previously identified in an AA GWAS study (p‐value=2.6×10‐6) (Kunkle et al, 2019). Here, we further characterize this locus and its role in AD.
Method
We performed region‐wide association analysis in an independent REAAADI dataset of ∼240 cases and ∼650 controls to fine map the signal in the locus. Additionally, we analyzed the WGS data to prioritize variants in the consensus regions based on segregation with disease among affected individuals and rarity (MAF<0.01). All variants were annotated for putative function including protein changes for coding variants and evidence for regulatory activity (ENCODE, RoadMap Epigenome) and chromatin interactions (publicly available HiC and promoter capture C) for noncoding variants.
Result
Region‐wide association analysis identified two regions of rare (MAF∼0.01) variants downstream (p=3.0×10‐8) and upstream (p=3.7×10‐6) of the 1‐LOD linkage region. Segregation analysis using WGS data identified 111 rare variants (MAF<0.01) segregating with disease in the AD individuals of the family with the highest LOD score contributing to the linkage peak. These include a 3’UTR and synonymous variant in INSYN2B/FAM196B as well as a promoter variant in WWC1/KIBRA. Interestingly, four other AA families contributing to the chr5 linkage signal harbor different within‐family shared variants located in INSYN2B’s promoter or in enhancer regions with evidence for interaction with INSYN2B’s promoter. WWC1, expressed in astrocytes, was previously reported in AD context, whereas novel candidate INSYN2B encodes an inhibitory synaptic factor active in oligodendrocytes and neurons.
Conclusion
Our initial analyses provide evidence for two candidate genes contributing to AD genetics in the AA population. Additional work for functional validation of these candidates for AD is ongoing. This AA population‐specific finding shows the importance of diversifying population‐level genetic data to better understand the genetic determinants of AD on a global scale.
Background
Depression (DEP) is a known risk factor for . However, DEP symptoms vary by race‐ethnicity (e.g. greater somatization among African Americans). The relationship between DEP and AD ...progression in underrepresented groups is not well‐understood. We hypothesize that certain DEP symptoms will be associated with earlier AAO, and that this relationship is moderated by race‐ethnicity
Method
Self‐declared Non‐Hispanic White (NWH), African American (AA), and Hispanic (HI) participants with AD and CDR data were identified from a larger genetic study. Our dataset consisted of 549 persons with a self‐completed GDS (mean CDR = 0.6; 15% NWH, 43% AA, 42% HI), 334 persons with informant completed CSDD (CDR = 1.7; 41% NWH, 20% AA, 39% HI), and 266 persons with self‐reported DEP and anxiety in a medical history exam (CDR = 0.7; 26% NWH, 23% AA, 51% HI). All measures were completed after the onset of AD. Univariate linear regressions examined the relationship between AAO and DEP (total scores and individual items), and race‐ethnicity x DEP interactions after controlling for sex, race‐ethnicity, disease duration, and APOE‐e4.
Result
Self‐reported (p = 0.04), informant‐reported anxiety (CSDD) (p = 0.02), and self‐reports of feeling empty (GDS) (p = 0.02) were associated with an earlier AAO across all groups. Informant‐reports of poor self‐esteem (CSDD) was associated with an earlier AAO overall (p < 0.01), but an interaction showed that this was not significant in HI (p = 0.). Unique items associated with an earlier AAO in NHW included higher GDS total scores (p = 0.01), feeling bored (GDS) (p < 0.01), and perceived problems with memory (GDS) (p < 0.01). In AA self‐reported DEP was associated with an earlier AAO (p = 0.02). No items were uniquely associated with AAO in HI.
Conclusion
Self‐ and informant‐reported anxiety and self‐reported feelings of emptiness were associated with an earlier AAO in all groups. However, several DEP symptoms associated with earlier AAO differed as a function of race‐ethnicity. We believe our findings suggest that the occurrence of DEP may be culturally or ancestrally influenced, which in turn has a differential impact on AAO in underrepresented groups.
Autism spectrum disorder (ASD) represents a heterogenous cluster of clinical phenotypes that are classically diagnosed by the time of adolescence. The possibility of late-life emergence of ASD has ...been poorly explored.
To more fully characterize the possibility of late-life emergence of behaviors characteristic of ASD in mild cognitive impairment and AD, we surveyed caregivers of 142 older persons with cognitive impairment from the University of Kentucky Alzheimer's Disease Center Longitudinal Cohort using the Gilliam Autism Rating Scale-2.
Participants with high autism index ratings (autism "possible/very likely," n=23) reported significantly (statistically and clinically) younger age at the onset of cognitive impairment than those who scored in the autism "unlikely" range (n=119): 71.14±10.9 vs. 76.65±8.25 (P=0.034). In addition, those in the autism "possible/very likely" group demonstrated advanced severity of cognitive impairment, indicated by the Clinical Dementia Rating Scale Sum of Boxes scores.
Data demonstrate that ASD behaviors may seem de novo of degenerative dementia and such behaviors are more prevalent in those with early onset dementia. Further work elucidating a connection between ASD and dementia could shed light on subclinical forms of ASD, identify areas of shared neuroanatomic involvement between ASD and dementias, and provide valuable insights that might hasten the development of therapeutic strategies.
Abstract
The normalization of memory loss continues to contribute to diagnostic delays among older adult African Americans with dementia. We utilized an innovative recruitment method to establish a ...solely online study to examine perceptions and knowledge levels of Alzheimer’s Disease in a highly educated geographically diverse cohort of 223 African Americans aged 50-84. Participants were recruited through largely electronic communications. Sample participants were primarily female (n=196), with 51.1% having completed a master’s degree, and 58.2% of participants with household incomes of $90,000 or higher. Study findings revealed that although highly educated, 42% of sample participants believed significant memory loss was a normal part of aging and 59.6% felt that God’s Will was a possible cause of AD. A sizable majority of participants, 86.5%, felt most family physicians were not trained to diagnose AD. Findings underscore the need for physician and community education within diverse populations, regardless of education and SES status.
Abstract
Background
Individuals with Down syndrome (DS) are at high risk for dementia, specifically Alzheimer’s disease (AD). However, many measures regularly used for the detection of AD in the ...general population are not suitable for individuals with DS. Some measures, including the Severe Impairment Battery (SIB), Brief Praxis Test (BPT), and Dementia Questionnaire for Persons with Intellectual Disabilities (DMR), have been used in clinical trials and other research with this population. Validity research is limited, however, particularly regarding identification of predementia symptoms in the DS population. The current project presents baseline cross‐sectional SIB, BPT, and DMR performance in order to characterize their ability to discriminate normal cognition, possible AD, and probable AD in DS.
Method
Baseline SIB, BPT, and DMR performances from 117 individuals were analyzed as part of a large longitudinal cohort of aging individuals with DS. Receiver operating characteristic (ROC) curves were calculated to investigate accuracy in differentiating levels of dementia status.
Result
In comparing no/possible AD vs. probable AD, the SIB and BPT exhibited fair discrimination ability (AUC = .78 and .79, respectively). In comparing no/possible AD vs. probable AD, the DMR exhibited good discrimination ability (AUC = .89), with qualitatively similar performance of the DMR‐Cognitive and DMR‐Social subscales (AUC = .89 and .83, respectively). In comparing no AD vs. possible AD, the SIB and BPT failed to differentiate these groups (AUC = .53 and .55, respectively), whereas the DMR exhibited good differentiation (AUC = .80).
Conclusion
Results suggest that the SIB, BPT, and DMR are able to discriminate between levels of dementia status in individuals with DS, supporting their continued use in the clinical assessment of dementia in DS. Specifically, the DMR, based on informant ratings of social and cognitive behaviors of daily living, outperformed the SIB and BPT, tests of cognitive performance, in discriminating no/possible AD vs. probable AD as well as no AD vs. possible AD. Such findings suggest that the DMR is better equipped to identify symptoms of overt dementia as well as predementia in this population. Findings reinforce the importance of including informant behavior ratings in assessment of this population.
Background
Subjective cognitive decline (SCD) is associated with objective cognitive decline, incident cognitive impairment, and AD pathology in mostly white populations. Little data are available to ...describe SCD and objective cognitive impairment in diverse populations.
Method
The Multi‐Ethnic Study of Atherosclerosis (MESA) began cognitive testing, including the Cognitive Abilities Screening Instrument (CASI), in 2010‐12 among four racial/ethnic groups: 38% white, 28% African‐American, 22% Hispanic, and 12% Chinese Americans across six field centers. MESA‐MIND and ancillary studies added repeated CASI by in‐person exam (2016‐2018) and the 12‐item Cognitive Change Index (CCI‐12) during the 2018 annual follow‐up call. Statistical analyses using the CCI‐12 item sum and two published thresholds (CCI‐12≥16 and CCI‐12≥23) established the point prevalence for SCD across racial/ethnic groups. Socio‐demographic factors were examined using multivariable logistic regression. Spearman correlations and general linear models related 5‐year subjective change (CCI‐12) and objective change in cognitive performance (change in CASI) over the same time period.
Result
CCI‐12 data were available on 3,676 MESA participants (aged 60‐95) across all racial/ethnic groups and sites. Table 1 presents demographics, CCI‐12 scores, and CASI scores. The prevalence of SCD (CCI‐12≥16) across racial/ethnic groups ranged between 52% to 72%. There was a lower prevalence in African‐American and white and a higher prevalence in Chinese and Hispanic participants. In adjusted models, various socio‐demographic factors were significantly associated with a higher odds of reporting SCD (CCI‐12≥16), including: older age, female gender, Chinese language preference, diabetes, smoking, birth in the Western US or Mexico, and lacking health insurance coverage. African‐American ethnicity, higher education, and income greater than $75,000 were each associated with a lower reporting of SCD. CCI‐12 was weakly and inversely correlated with antecedent cognitive performance (2010‐12, n=3,200, Rho=‐0.16, p<0.01) and cognitive decline (n=1,800, Rho=‐0.06, p=0.01) over 6 years of follow‐up. In stratified analyses, associations between CCI‐12 and objective cognitive decline were observed in white participants only.
Conclusion
In a large regionally and ethnically diverse cohort of older adults, SCD defined by subjective memory concerns on the CCI‐12 significantly differed by race/ethnicity and indicators of socioeconomic status, suggesting that cultural and institutional biases may influence reporting SCD in diverse populations.
Abstract
Background
Subjective cognitive decline (SCD) is associated with objective cognitive decline, incident cognitive impairment, and AD pathology in mostly white populations. Little data are ...available to describe SCD and objective cognitive impairment in diverse populations.
Method
The Multi‐Ethnic Study of Atherosclerosis (MESA) began cognitive testing, including the Cognitive Abilities Screening Instrument (CASI), in 2010‐12 among four racial/ethnic groups: 38% white, 28% African‐American, 22% Hispanic, and 12% Chinese Americans across six field centers. MESA‐MIND and ancillary studies added repeated CASI by in‐person exam (2016‐2018) and the 12‐item Cognitive Change Index (CCI‐12) during the 2018 annual follow‐up call. Statistical analyses using the CCI‐12 item sum and two published thresholds (CCI‐12≥16 and CCI‐12≥23) established the point prevalence for SCD across racial/ethnic groups. Socio‐demographic factors were examined using multivariable logistic regression. Spearman correlations and general linear models related 5‐year subjective change (CCI‐12) and objective change in cognitive performance (change in CASI) over the same time period.
Result
CCI‐12 data were available on 3,676 MESA participants (aged 60‐95) across all racial/ethnic groups and sites. Table 1 presents demographics, CCI‐12 scores, and CASI scores. The prevalence of SCD (CCI‐12≥16) across racial/ethnic groups ranged between 52% to 72%. There was a lower prevalence in African‐American and white and a higher prevalence in Chinese and Hispanic participants. In adjusted models, various socio‐demographic factors were significantly associated with a higher odds of reporting SCD (CCI‐12≥16), including: older age, female gender, Chinese language preference, diabetes, smoking, birth in the Western US or Mexico, and lacking health insurance coverage. African‐American ethnicity, higher education, and income greater than $75,000 were each associated with a lower reporting of SCD. CCI‐12 was weakly and inversely correlated with antecedent cognitive performance (2010‐12, n=3,200, Rho=‐0.16, p<0.01) and cognitive decline (n=1,800, Rho=‐0.06, p=0.01) over 6 years of follow‐up. In stratified analyses, associations between CCI‐12 and objective cognitive decline were observed in white participants only.
Conclusion
In a large regionally and ethnically diverse cohort of older adults, SCD defined by subjective memory concerns on the CCI‐12 significantly differed by race/ethnicity and indicators of socioeconomic status, suggesting that cultural and institutional biases may influence reporting SCD in diverse populations.
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