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3 Ethnoracial Differences in Anchor Agreement and MCID Estimation in Alzheimer’s Disease
- Samantha E John, Stacey Moeller, Denise Tanner
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 506-507
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Objective:
Alzheimer’s disease (AD) clinical trials lack diverse representation, limiting their generalizability. In addition, the clinical meaningfulness of observed changes during treatment may vary as a function of participant characteristics. Defining meaningful change in AD within diverse ethnoracial groups is therefore greatly needed. Meaningful change in AD trials can be assessed by three different anchors: participants, informants, or clinicians. Previous research has suggested that estimations of the minimal clinically important difference (MCID) vary by disease severity, choice of anchor, and anchor agreement. These relationships have been studied primarily within non-Hispanic white (NHW) samples. This project evaluates anchor-based MCID within and across the three most prevalent ethnoracial groups in the United States, non-Hispanic White (NHW), Hispanic/Latino (H/L), and Black/African-American (B/AA).
Participants and Methods:Data from the National Alzheimer’s Coordinating Center Uniform Dataset (NACC UDS) were used to investigate MCID within older adults (ages 50+) diagnosed as cognitively normal or cognitively impaired due to suspected AD. Data were taken from all versions of the UDS and consisted of all available participants with two consecutive annual visits. The identified sample (N=22,043) is approximately 83.6% NHW, 4.7% H/L, and 11.7% B/AA. Participant, informant, and clinician anchor variables were utilized to compare proportions of anchor agreement within and across ethnoracial groups. MCID on the Mini-Mental State Exam (MMSE) was estimated within each ethnoracial group and compared across the independent variables of anchor agreement and disease severity (cognitively normal (CN), mild cognitive impairment (MCI), and dementia) in 2x3 ANOVAs.
Results:Participant age (M = 71.56, SD = 9.03) did not significantly differ across ethnoracial groups; years of education significantly differed across groups, p < .001, with NHW (M=15.83 SD=3.05), H/L (M=12.49, SD=5.01), and B/AA (M=14.42, SD=3.22). Across all three anchors (participant, informant, clinician), unanimous agreement about the presence or absence of a decline in functioning was present in about 75.1% of the full sample. To further explore agreement differences across groups, anchor agreement was classified into a 3-level variable: 1) agreement that the participant remained stable over time, 2) agreement that the participant declined, and 3) disagreement. The proportion of each level within each ethnoracial group was significantly different, (x2(4, n = 22,043) = 179.16, p < .001, phi = .09, NHW (34.5% agreement-stable, 41.4% agreement-declined, 24.1% disagreement), H/L (30.5%, 42.6%, 26.9%, respectively), and B/AA (42.2%, 28.1%, 29.7%, respectively). MCID estimates on the MMSE followed similar trends within each ethnoracial group. There was a significant main effect of disease severity, such that MCID estimates increased in magnitude with increasing disease severity. There were no significant main effects of anchor agreement for any ethnoracial group. Within the NHW sample only, an interaction effect between diagnostic severity and anchor agreement was significant (p = .007).
Conclusions:Across ethnoracial groups, MCID estimates on the MMSE are reliably influenced by the severity of disease. However, the benefit of anchor-based MCID estimates may vary by ethnoracial group with respect to both anchor choice and use of anchor agreement. The origins of anchor disagreement and perceived stability in functioning warrant further exploration.
3 Network Analysis of Neuropsychiatric Symptoms in Alzheimer’s Disease
- Grace J Goodwin, Stacey Moeller, Amy Nguyen, Samantha John
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 517-518
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Objective:
Neuropsychiatric symptoms due to Alzheimer’s disease (AD) and mild cognitive impairment (MCI) can decrease quality of life for patients and increase caregiver burden. Better characterization of neuropsychiatric symptoms is needed to identify effective treatment targets. The current investigation leveraged the National Alzheimer’s Coordinating Center (NACC) Uniform Data Set (UDS) to examine the network structure of neuropsychiatric symptoms among symptomatic older adults with cognitive impairment.
Participants and Methods:The identified sample includes those from the NACC UDS (all versions) with complete data on the Neuropsychiatric Inventory Questionnaire (NPI-Q) at initial visit. The NPI-Q is an informant-based estimation of the presence and severity of neuropsychiatric symptoms (delusions, hallucinations, agitation or aggression, depression or dysphoria, anxiety, elation or euphoria, apathy or indifference, disinhibition, irritability or lability, motor disturbance, nighttime behaviors, appetite and eating problems). The following inclusionary criteria were applied for sample identification: age 50+; cognitive status of MCI or dementia; AD was the primary or contributing cause of observed impairment; and at least one symptom on the NPI-Q was endorsed. Participants were excluded if they endorsed “unknown” or “not available” on any NPI-Q items. The final sample (n = 12,507) consisted of older adults (Mage=73.94, SDage=9.41; 46.2% male, 53.8% female) who predominantly identified as non-Hispanic white (NHW) (74.5% NHW, 10.9% non-Hispanic Black, 8.5% other, 5.8% Hispanic white, .3% Hispanic Black). The majority of the sample met criteria for dementia (77.6% dementia, 22.4% MCI) and AD was the presumed primary etiology in 93.9%.
The eLasso method was used to estimate the binary network, wherein nodes represent NPI-Q variables and edges represent their pairwise dependency after controlling for all other symptom variables in the network. In other words, the network represents the conditional probability of an observed binary variable (e.g., presence/absence of delusions) given all other measured variables (e.g., presence/absence of all other NPI-Q symptoms) (Finnemann et al., 2021; van Borkulo et al., 2014). Strength centrality and expected influence were calculated to determine relative importance of each symptom variable in the network. Network accuracy was examined with methods recommended by Epskamp et al. (2018), including edge-weight accuracy, centrality stability, and difference tests.
Results:Edge weights and node centrality (CS(cor=.7)=.75) were stable and interpretable. The network (M=.28) consisted of mostly positive edges and some negative edges. The strongest edges linked nodes within symptom domain (e.g., strong positive associations among externalizing symptoms). Disinhibition and agitation/aggression were the most central and influential symptoms in the network, respectively. Depression or dysphoria was the most frequently endorsed symptom, followed by anxiety, apathy or indifference, and irritability or lability.
Conclusions:Endorsed disinhibition and agitation yielded a higher probability of additional neuropsychiatric symptoms and influenced the activation, persistence, and remission of other neuropsychiatric symptoms within the network. Thus, interventions targeting these symptoms may lead to greater neuropsychiatric symptom improvement overall. Depression or dysphoria, while highly endorsed, was least influential in the network. This may suggest that depression and dysphoria are common, but not central neuropsychiatric features of AD pathology. Future work will compare neuropsychiatric symptom networks across racial and ethnic groups and between MCI and dementia.