To determine in a large multiethnic cohort the cardiovascular and genetic risk factors associated with smaller volume in the hippocampus, precuneus, and posterior cingulate, and their association with preclinical deficits in cognitive performance in patients younger and older than 50 years.The institutional review board approved the study and all participants provided written informed consent. Eligible for this study were 1629 participants (700 men and 929 women; mean age, 50.0 years ± 10.2 [standard deviation]) drawn from the population-based Dallas Heart Study who underwent laboratory and clinical analysis in an initial baseline visit and approximately 7 years later underwent brain magnetic resonance imaging with automated volumetry and cognitive assessment with the Montreal Cognitive Assessment (MoCA). Regression analysis showed associations between risk factors and segmental volumes, and associations between these volumes with cognitive performance in participants younger and older than 50 years.Lower hippocampal volume was associated with previous alcohol consumption (standardized estimate, -0.04; P = .039) and smoking (standardized estimate, -0.04; P = .048). Several risk factors correlated with lower total brain, posterior cingulate, and precuneus volumes. Higher total (standardized estimate, 0.06; P = .050), high-density lipoprotein (standardized estimate, 0.07; P = .003), and low-density lipoprotein (standardized estimate, 0.04; P = .037) cholesterol levels were associated with larger posterior cingulate volume, and higher triglyceride levels (standardized estimate, 0.06; P = .004) were associated with larger precuneus volume. Total MoCA score was associated with posterior cingulate volume (standardized estimate, 0.13; P = .001) in younger individuals and with hippocampal (standardized estimate, 0.06; P < .05) and precuneus (standardized estimate, 0.08; P < .023) volumes in older adults.Smaller volumes in specific brain regions considered to be early markers of dementia risk were associated with specific cardiovascular disease risk factors and cognitive deficits in a predominantly midlife multiethnic population-based sample. Additionally, the risk factors most associated with these brain volumes differed in participants younger and older than 50 years, as did the association between brain volume and MoCA score.
This study examined whether history of traumatic brain injury (TBI) is associated with increased risk and earlier onset of mild cognitive impairment (MCI). Subjects with MCI (n = 3,187) and normal cognition (n = 3,244) were obtained from the National Alzheimer's Coordinating Center database. TBI was categorized based on lifetime reported TBI with loss of consciousness (LOC) without chronic deficit. Logistic regression was used to examine TBI history as a predictor of MCI, adjusted for demographics, apolipoprotein E-ɛ4 (ApoE4), a composite vascular risk score, and history of psychiatric factors. ANCOVA was used to examine whether age at MCI diagnosis and estimated age of onset differed between those with (TBI+) and without (TBI-) a history of TBI. TBI history was a significant predictor (p < 0.01) and associated with increased odds of MCI diagnosis in unadjusted (OR = 1.25; 95% CI = 1.05-1.49) and adjusted models, accounting for age, education, ApoE4, and a composite vascular score (OR = 1.32; 95% CI = 1.10-1.58). This association, however, was largely attenuated (OR = 1.14; 95% CI = 0.94-1.37; p = 0.18) after adjustment for reported history of depression. MCI was diagnosed a mean of 2.3 years earlier (p < 0.001) in the TBI+ group, and although TBI+ subjects had an estimated mean of decline 1.7 years earlier, clinician-estimated age of onset failed to differ (p = 0.13) when gender and psychiatric factors were controlled. This is the first report of a possible role for TBI as a risk factor in MCI, but its association may be related to other factors such as gender and depression and requires further investigation.
Background: Life expectancy (LE) following Alzheimer’s disease (AD) is highly variable. The literature to date is limited by smaller sample sizes and clinical diagnoses. Objective: No study to date has evaluated predictors of AD LE in a retrospective large autopsy-confirmed sample, which was the primary objective of this study. Methods: Participants (≥50 years old) clinically and neuropathologically diagnosed with AD were evaluated using National Alzheimer’s Coordinating Center (N = 1,401) data. Analyses focused on 21 demographic, medical, neuropsychiatric, neurological, functional, and global cognitive predictors of LE at AD dementia diagnosis. These 21 predictors were evaluated in univariate analyses. Variables found to be significant were then entered into a forward multiple regression. LE was defined as months between AD diagnosis and death. Results: Fourteen predictors were significant in univariate analyses and entered into the regression. Seven predictors explained 27% of LE variance in 764 total participants. Mini-Mental State Examination (MMSE) score was the strongest predictor of LE, followed by sex, age, race/ethnicity, neuropsychiatric symptoms, abnormal neurological exam results, and functional impairment ratings. Post-hoc analyses revealed correlations of LE were strongest with MMSE ≤12. Conclusion: Global cognitive functioning was the strongest predictor of LE following diagnosis, and AD patients with severe impairment had the shortest LE. AD patients who are older, male, white, and have more motor symptoms, functional impairment, and neuropsychiatric symptoms were also more likely have shorter LE. While this model cannot provide individual prognoses, additional studies may focus on these variables to enhance predictions of LE in patients with AD.
Abstract Objective Research examining the course of Alzheimer’s disease (AD) in Hispanics is lacking. This study examined demographic, psychiatric, cognitive, and genetic predictors of longitudinal functional change in Hispanics and non-Hispanics with AD. Method Longitudinal change in instrumental activities of daily living (IADL) was examined over 10 years (M = 4.15 years) in 292 subjects (Hispanic = 67, non-Hispanic = 225). All were part of the Texas Alzheimer’s Research & Care Consortium and included those with AD (n = 217) and those with mild cognitive impairment at baseline who progressed to AD at follow-up (n = 75). Baseline comparisons were conducted between ethnic groups for demographics, Geriatric Depression Scale (GDS-30) score, Mini Mental State Examination (MMSE) score, presence of apolipoprotein ɛ4 alleles (APOE4), and annualized IADL change scores and then entered into a multiple linear regression model as predictors of annualized IADL change. Results The Hispanic group had significantly more females (χ2 = 5.71, p = .017), lower education [MH = 9.96(4.39), MNH = 15.26(2.70)], higher depression scores [GDS-30; MH = 9.45(5.89), MNH = 5.51(4.29)], lower MMSE scores [MH = 23.31(4.33), MNH = 24.65(3.21)], and slower annualized IADL change [MH = 1.19(1.42), MNH = 2.02(1.60)]. Regression results were significant (F = 3.66, p = .001, R2 = .08 ), with higher baseline MMSE (p = .007) and Hispanic origin (p = .010) predicting slower annualized IADL change. Demographics, APOE4 status, and depression did not significantly predict IADL change. Conclusions Higher cognitive functioning at baseline and Hispanic origin was associated with slower functional decline over an average 4-year period of time. Despite having lower MMSE scores at baseline, greater depression, and less education, the Hispanic group had a slower decline in IADLs compared to non-Hispanics. Further research is needed to better understand how/why Hispanic origin is associated with slower functional decline.
Determine if head-injury exposure relates to later-in-life cognitive decline in older National Football League (NFL) retirees.NFL retirees (aged 50+) with or without cognitive impairment underwent baseline (n = 53) and follow-up (n = 29; 13-59 months later) neuropsychological evaluations. Cognitively normal (CN) retirees (n = 26) were age- and education-matched to healthy controls (n = 26). Cognitively impaired (CI) retirees with mild cognitive impairment or dementia (n = 27) were matched to a clinical sample (CS) by age, sex, education, and diagnosis (n = 83). ANOVAs compared neuropsychological composites at baseline and over time between retirees and their matched groups. Regression models evaluated whether concussions, concussions with loss of consciousness (LOC), or games played predicted neuropsychological functioning.At baseline, CN retirees had slightly worse memory than controls (MCN retirees = 50.69, SECN retirees = 1.320; MHealthy controls = 57.08, SEHealthy controls = 1.345; p = 0.005). No other group diferences were observed, and head-injury exposure did not predict neurocognitive performance at baseline or over time.Head-injury exposure was not associated with later-in-life cognition, regardless of cognitive diagnosis. Some retirees may exhibit lower memory scores compared to age-matched peers, though this is of unclear clinical significance.
Abstract Background Previous research has demonstrated a link between objective socio‐economic indicators and cognitive test performance. Although some studies include subjective indicators, such as perceived neighborhood environment, little is known about which specific factors are most strongly associated with cognitive performance and whether these measures are useful beyond traditional SES proxies. Further, in addition to being disproportionately at risk of experiencing neighborhood disadvantage and lower SES, racial/ethnic minorities are more likely to be diagnosed with dementia and receive less timely care compared with White individuals. This study aims to investigate how perceived neighborhood environment and neighborhood disadvantage are related to cognitive performance within a large diverse sample. Method A probability‐based sample of participants (N = 3858; Female = 59%; Black = 51%; Hispanic = 14%) from the Dallas Heart Study Phase 2 (DHS‐2; Mean: Age = 50, Education = 13) were administered the Montreal Cognitive Assessment (MoCA), in addition to measures of perceptions of neighborhood physical environment and violence, and perceived SES. Multiple regression was used to determine associations of these variables with MoCA scores relative to traditional SES measures (i.e., income, education), controlling for demographic and relevant health factors. Post‐hoc analyses stratified by racial/ethnic group were conducted to determine whether indicators differentially influenced test scores. Result After controlling for socio‐demographic and health factors, reporting lower quality neighborhood resources and difficulty paying for “very basics like food and heating” and “medical care” were associated with lower MoCA scores in the overall sample. Post‐hoc analyses revealed significant relationships between MoCA scores and quality of neighborhood resources, “food and heating,” and “medical care” only in Black participants, while “violence” was significantly associated with lower MoCA scores in Hispanics. There were no significant relationships found in Whites. Overall, subjective measures of SES and neighborhood environment contributed modest variance in the overall model, specifically for Black and Hispanic participants ( R 2 = 3% to 5%). Conclusion Experiencing neighborhood and economic adversity was associated with lower scores on a cognitive screening measure and accounted for more variance than income or education in Black individuals and income in Hispanic individuals, while no relationship was seen in White participants. Future research is needed to determine whether these allostatic stressors influence cognitive impairment or dementia later in life.
Objective: Higher baseline dispersion (intra-individual variability) across neuropsychological test scores at a single time-point has been associated with more rapid cognitive decline, onset of Mild Cognitive Impairment (MCI) and Alzheimer’s disease (AD), faster rates of hippocampal and entorhinal atrophy, and increased AD neuropathology. Comparison between predictions made from test score dispersion within a cognitive domain versus global, cross-domain dispersion is understudied. Global dispersion may be influenced by ability-and test-specific characteristics. This study examined the performance of global versus domain-specific dispersion metrics to identify which is most predictive of cognitive decline over time. Participants and Methods: Data for baseline and five follow-up visits of 308 participants with normal cognition (Mage=73.90, SD=8.12) were selected from the National Alzheimer’s Coordinating Center (NACC) Dataset. Participants were required to have no focal neurological deficits, or history of depression, stroke, or heart attack. Diagnoses and progression to MCI and/or dementia were determined at each visit through consensus conferences. Raw neuropsychological scores were standardized using NACC norms. Global baseline dispersion was defined as the intraindividual standard deviation (ISD) across the 10 scores in the NACC battery. Domain-specific dispersions were calculated by constructing composites and ISD was computed across tests sampling their respective domains (executive functioning/attention/processing speed [EFAS], language, and memory; see Table 1 for details on these tests). Higher values on each of these metrics reflect greater dispersion. Multinomial logistic regression model fit statistics and parameter estimates were compared across four different models (global, EFAS, Language, and Memory dispersion) covarying for age, years of education, sex, race, ethnicity, and ApoE4 status. Models were compared using the Likelihood Ratio Test (LRT) and the Akaike Information Criteria (AIC) of Models statistics. Results: Of the 308 participants, 70 (22.7%) progressed to MCI, and 82 (26.6%) progressed to dementia. Tables 1 and 2 show the results of the logistic regressions for the four models. All models fit the data well, with statistically significant predictions of conversion. Model 1 (global dispersion) showed a better fit than domain-specific models of dispersion per LRT and AIC values. Consistent with the results from mean differences between groups, parameter estimates showed that only global dispersion and EFAS dispersion significantly predicted conversion to dementia (when included with other covariates in models), with higher dispersion reflecting a greater risk of conversion. Conclusions: In this sample, baseline global and EFAS dispersion measures significantly predicted conversion to dementia. Although global dispersion was a stronger predictor of dementia progression, findings suggest that executive functioning performance may be driving this relationship. A single index of global variability, from the calculation of standard deviation across test scores, may be supplementary for clinicians when distinguishing individuals at risk for dementia progression. None of the models were predictive of conversion to MCI. Further research is required to examine cognitive variability differences among patients who progress to MCI and patient-specific factors that may relate to test score dispersion and its utility in predicting the progression of symptoms.
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Some children and adolescents have persistent concussion symptoms that extend beyond the typical 3–4 week recovery window. Our understanding about what to expect when recovery is atypical, particularly in elementary-age children, is incomplete because there are very few targeted studies of this age group in the published literature. Aims were to identify lingering symptoms that present at three months post-concussion and to determine what factors are associated with prolonged recovery in an elementary-age group. Participants were 123 children aged 5–10 years who were seen at specialized concussion clinics, divided into expected and late recovery groups. Parents rated concussion symptoms on a scale from the Sideline Concussion Assessment Tool-5 (SCAT-5). The most frequent symptoms were headache, irritability, feeling more emotional, and sensitivity to noise. Stepwise logistic regression determined that female sex and total symptom burden at initial visit, but not any specific symptom, predicted prolonged recovery. Clinicians are advised to carefully monitor children who report numerous symptoms after concussion, particularly when the concussed children are girls.
To evaluate whether a history of traumatic brain injury (TBI) with reported loss of consciousness (LOC) is a risk factor for earlier onset of Alzheimer's disease (AD) in an autopsy-confirmed sample.Data from 2,133 participants with autopsy-confirmed AD (i.e., at least Braak neurofibrillary tangle stages III to VI and CERAD neuritic plaque score moderate to frequent) were obtained from the National Alzheimer's Coordinating Center (NACC). Participants were categorized by presence/absence of self-reported remote (i.e., >1 year prior to their first Alzheimer's Disease Center visit) history of TBI with LOC (TBI+ vs. TBI-). Analyses of Covariance (ANCOVA) controlling for sex, education, and race compared groups on clinician-estimated age of symptom onset and age of diagnosis.Average age of onset was 2.34 years earlier (p = .01) for the TBI+ group (n = 194) versus the TBI- group (n = 1900). Dementia was diagnosed on average 2.83 years earlier (p = .002) in the TBI+ group (n = 197) versus the TBI- group (n = 1936). Using more stringent neuropathological criteria (i.e., Braak stages V-VI and CERAD frequent), both age of AD onset and diagnosis were 3.6 years earlier in the TBI+ group (both p's < .001).History of TBI with reported LOC appears to be a risk factor for earlier AD onset. This is the first study to use autopsy-confirmed cases, supporting previous investigations that used clinical criteria for the diagnosis of AD. Further investigation as to possible underlying mechanisms of association is needed. (PsycINFO Database Record
