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29 Vascular Burden Mediates the Relationship Between ADHD and Cognition in Older Adults
- Brandy L. Callahan, Sara Becker, Joel Ramirez, Rebecca Taylor, Prathiba Shammi, Sandra E. Black
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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. 637-638
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Objective:
Accumulating evidence from case-control and population studies suggests attention-deficit/hyperactivity disorder (ADHD) confers a 2- to 5-fold risk of all-cause dementia later in life. Here, we investigate vascular burden as a potential mediator of this relationship, because vascular integrity is well known to be compromised in ADHD (due to chronic obesity, diabetes, and hypertension) and is also a robust risk factor for neurodegeneration (due to reduced cerebral blood flow). We use brain white matter hyperintensities (WMH) as a measure of vascular burden.
Participants and Methods:Thirty-nine adults aged 48-81 years with clinical ADHD, and 37 matched controls, completed neuropsychological testing and 1.5 T structural neuroimaging. None had stroke. Cognitive tests were demographically-adjusted to Z scores using regression-based norms generated from the control group, and averaged across tests within domains of short- and long-term verbal memory (forward digit span, California Verbal Learning Test, Logical Memory), visual memory (Visual Recognition, Rey Complex Figure), processing speed (coding, trails A, Stroop word-reading and color-naming), language (Boston Naming Test, semantic fluency), visuoconstruction (clock drawing, Rey Complex Figure copy), and executive function (backward digit span, trails B, phonemic fluency, Stroop inhibition, Wisconsin Card Sorting Test). Total WMH volumes (i.e., combined periventricular and deep) within subcortical, temporal, frontal, parietal, and occipital regions were individually divided by regional volumes to produce a proportion of each region representing WMH, then log-transformed to correct for skew. Age-corrected linear regression quantified total effects of ADHD on cognition; when these were significant, mediation models quantified the direct effects of ADHD on WMH volumes and the direct effect of WMH volumes on cognition. Sobel’s test estimated indirect effects of ADHD on cognition via WMH.
Results:Group had a significant total effect on Processing Speed (ß=-1.154, p<.001) and on Executive Functioning (ß=-0.587, p=.004), where ADHD participants had lower composite scores (M=-1.10, SD=1.76 and M=-0.54, SD=1.14 respectively) than controls (M=0.02, SD=0.74; M=0.00, SD=0.49). Only frontal-lobe WMH had direct effects on Processing Speed (ß=-0.315, p=.012) and Executive Functioning (ß=-0.273, p<.001). The direct effect of ADHD on frontal WMH was significant (ß=-0.734, p=.016), and Sobel’s tests supported an indirect effect of ADHD on Executive Functioning (z=2.079, p=.038) but not Processing Speed (z=1.785, p=.074) via WMH. Because the effect of ADHD on WMH was negative (i.e., fewer WMH in ADHD) despite worse cognition than controls, we tested the a posteriori hypothesis that WMH burden may be relatively more deleterious for ADHD than controls. We found considerably stronger negative correlations between total WMH volumes and Processing Speed (r=-.423, p=.009) and Executive Functioning (r=-.528, p<.001) in the ADHD group than in controls (r=-.231, p=.175 and r=-.162, p=.346, respectively), even though total whole-brain proportion of WMH (M=0.15%, SD=0.27; Mann-Whitney l/=430.0, p=.002) and frontal-lobe proportion of WMH volumes (M=0.33%, SD=0.51; Mann-Whitney U=464.0, p=.007) were lower in ADHD than in controls (M=0.29%, SD=0.42 and M=0.66%, SD=0.88, respectively).
Conclusions:WMH burden contributes significantly to the relationship between ADHD and cognition, but ADHD remains an independent contributor to worse processing speed and executive functioning in older adults. Vascular burden may have relatively more deleterious effects on cognition in ADHD, potentially due to decades of accumulated allostatic load, whereas healthy controls can accumulate greater amounts of WMH before cognition is impacted.
66 Association of Executive Functions and Instrumental Activities of Daily Living in Parkinson’s Disease
- Sara Becker, Nadia Maarouf, Mekale Kibreab, Tracy Hammer, Iris Kathol, Oury Monchi, Brandy L Callahan
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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. 576-577
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Objective:
Executive function (EF) abilities tend to decline with age, and disproportionately so for people with neurodegenerative disorders such as Parkinson’s Disease (PD), where EF deficits are commonly seen in the early stages of the disease. Due to their nature, EF are essential for performing tasks of daily life, particularly for the more complex instrumental activities of daily living (IADL), and deficits can impair the ability to execute IADL in PD participants. The aim of this study was to examine how EF impairments relate to IADL deficits in both healthy elderly controls and PD participants.
Participants and Methods:Seventy-four participants with idiopathic PD and 66 elderly controls were recruited. All participants were non-demented. A comprehensive neuropsychological assessment was administered including the following measures of EF: Hayling Sentence Completion, Brixton Spatial Anticipation, Trail Making Test A and B, Stroop Color-Word Test, Symbol Span (Wechsler Memory Scale-III), Digit Span (Wechsler Adult Intelligence Scale-III), F-A-S test, and Semantic Fluency (Animals and Actions). Z scores were calculated from respective test manuals. Independence was measured using the 8-item Lawton IADL Scale where items are coded from 0 (dependent) to 1 (independent) and the total score ranges from 0 to 8. Motor impairments were assessed using Part III of the Movement Disorder Society Unified Parkinson’s Disease Rating Scale. Regression models were run with each cognitive measure as the dependent variable, with group (control vs. PD), age, sex, education, and motor severity as predictors, to examine the effect of group on each cognitive variable. Correlations were then run between the total IADL score, demographic variables, and cognitive variables for each participant group separately to identify the relationship between IADL and EF measures.
Results:PD participants were predominantly males (n=51, 68.9%), with an average age of 70.64±6.03 and 15.22±2.78 education years. Controls were predominantly female (n=34, 51.5%) and had an average age of 71.19±7.75 and 15.85±2.82 education years. Regarding IADL function, all participants were relatively independent in their IADLs (PD: 7.72±0.69, range 4-8, Controls: 7.98±0.13, range 7-8). The most difficult IADL items for PD participants were shopping (8.2% dependent) and food preparation (12.2% dependent). When correcting for age, education, sex, and motor severity, only the Stroop Interference z-score was significant for participant group (b=0.44, t=2.14, p=0.034), where controls had slightly lower scores (-0.33±0.77) than PD participants (-0.31±0.91). Correlations in controls were significant between IADL total score and Hayling trials 1 (r=0.35, p=0.005) and 2 (r=0.33, p=0.008), and semantic fluency actions trial (r=0.34, p=0.006). In PD participants, IADL total score was only correlated with semantic fluency (animals trial, r=0.26, p=0.028).
Conclusions:There were only weak associations between EF abilities and IADL in both healthy controls and PD participants, suggesting that impairments in EF do not necessarily translate into worse ability to execute IADL in PD. More correlations were found in the control group, which may be confounded by the inclusion (in both groups) of participants who already had cognitive impairment. This highlights a further need to examine whether EF impairments in people with PD influence IADL functioning above and beyond normal aging and whether specific deficits have more real-life consequences not attainable through IADL questionnaires.
Sex differences in risk factors that predict progression from mild cognitive impairment to Alzheimer’s dementia
- Courtney Berezuk, Maleeha Khan, Brandy L. Callahan, Joel Ramirez, Sandra E. Black, Konstantine K. Zakzanis, for the Alzheimer’s Disease Neuroimaging Initiative
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue 4 / May 2023
- Published online by Cambridge University Press:
- 15 August 2022, pp. 360-368
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Objectives:
To evaluate whether cerebrospinal fluid biomarkers, apolipoprotein e4, neuroimaging abnormalities, and neuropsychological data differentially predict progression from mild cognitive impairment (MCI) to dementia for men and women.
Methods:Participants who were diagnosed with MCI at baseline (n = 449) were classified as either progressing to Alzheimer’s dementia at follow-up or as not progressing. Men and women were first compared using bivariate analyses. Sex-stratified Cox proportional hazard regressions were performed examining the relationship between baseline data and the likelihood of progressing to dementia. Sex interactions were subsequently examined.
Results:Cox proportional hazard regression controlling for age and education indicated that all variables significantly predicted subsequent progression to dementia for men and women. Sex interactions indicated that only Rey Auditory Verbal Learning Test (RAVLT) delayed recall and Functional Activities Questionnaire (FAQ) were significantly stronger risk factors for women. When all variables were entered into a fully adjusted model, significant risk factors for women were Aβ42, hippocampal volume, RAVLT delayed recall, Boston Naming Test, and FAQ. In contrast, for men, Aβ42, p-tau181, p-tau181/Aβ42, hippocampal volume, category fluency and FAQ were significant risk factors. Interactions with sex were only significant for p-tau181/Aβ42 and RAVLT delayed recall for the fully adjusted model.
Conclusions:Men and women with MCI may to differ for which factors predict subsequent dementia although future analyses with greater power are needed to evaluate sex differences. We hypothesize that brain and cognitive reserve theories may partially explain these findings.
Operationalizing Impaired Performance in Neuropsychological Assessment: A Comparison of the Use of Published Versus Sample-Based Normative Data for the Prediction of Dementia
- Brandy L. Callahan, for the Alzheimer’s Disease Neuroimaging Initiative
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- Journal:
- Journal of the International Neuropsychological Society / Volume 26 / Issue 6 / July 2020
- Published online by Cambridge University Press:
- 11 December 2019, pp. 624-631
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Objectives:
To compare the sensitivity, specificity, and predictive value of published versus sample-based norms to detect early dementia in the Uniform Data Set (UDS).
Methods:The UDS was administered to 526 nondemented participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Baseline scores were standardized using published norms and healthy control data from ADNI corrected for age, education, and sex. Subjects obtaining two scores < −1 SD (determined separately using published and sample norms) were labeled “at risk for dementia.” Both methods were compared on sensitivity, specificity, and positive/negative predictive value (PPV/NPV) for dementia at follow-up.
Results:Risk scores derived from published data had 86.1% sensitivity, 62.0% specificity, 68.6% accuracy, 46.1% PPV, and 92.2% NPV. Those from sample norms were more sensitive (91.0%), less specific (52.9%), and less accurate (63.3%), with worse PPV (42.1%) and similar NPV (94.0%). Sample norms were better at identifying incident dementia cases with relatively lower education than those with higher education. Discrepancies between both methods were more common in women.
Conclusions:Sample norms are marginally more sensitive than published norms for predicting dementia, while published norms are slightly more accurate. Accuracy of risk estimates for women and those with lower education may be increased using locally generated norms.
Examining the validity of the ADHD concept in adults and older adults
- Brandy L. Callahan, André Plamondon
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- Journal:
- CNS Spectrums / Volume 24 / Issue 5 / October 2019
- Published online by Cambridge University Press:
- 08 October 2018, pp. 518-525
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Objective
It is crucial to clarify the structure of attention-deficit/hyperactivity disorder (ADHD) symptomatology in all age groups to determine how to best conceptualize this disorder across the lifespan. We tested the ADHD factor structure across adulthood and investigated independent associations with executive functions.
MethodData from 645 adults aged 18–59 and 233 adults aged 60–85 were drawn from the Nathan Kline Institute Rockland Sample. Participants completed the Conners Adult ADHD Rating Scale and tests of executive functioning. Invariance of the ADHD factor structure was investigated using confirmatory factor analyses. Associations with cognition were explored using multiple linear regression.
ResultsResults confirmed a bifactor model with 3 specific factors (inattention, hyperactivity, and impulsivity). Factor loadings and item intercepts were invariant across ages. Levels of hyperactivity and impulsivity were lower in older adults. Inattentive symptoms in young adults were positively related to cognitive flexibility. In older adults, ADHD symptoms predicted poorer working memory.
ConclusionADHD symptoms manifest similarly across adulthood. The lack of robust associations between ADHD symptomatology and executive functions raises concerns about the usefulness of neuropsychological measures in diagnosing adult ADHD. These results support the validity of the ADHD concept in older adults but suggest a need for age-appropriate normative criteria.
Memory for emotional images differs according to the presence of depressive symptoms in individuals at risk for dementia
- Brandy L. Callahan, Robert Laforce, Jr., Michel Dugas, Carol Hudon
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- Journal:
- International Psychogeriatrics / Volume 29 / Issue 4 / April 2017
- Published online by Cambridge University Press:
- 15 December 2016, pp. 673-685
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Background:
Studies of amnestic mild cognitive impairment (aMCI) and late-life depression (LLD) have examined the similarities and differences between these syndromes, but few have investigated how the cognitive profile of comorbid aMCI and subclinical depressive symptoms (aMCI/D+) may compare to that of aMCI or LLD. Memory biases for certain types of emotional information may distinguish these groups.
Methods:A total of 35 aMCI, 23 aMCI/D+, 13 LLD, and 17 elderly controls (CONT) rated the valence (positive, negative, or neutral) of 30 pictures from the International Affective Picture System. Mean percent positive, negative, and neutral images recalled was compared within groups immediately and 30 minutes later.
Results:Overall memory performance was comparable in aMCI and aMCI/D+, and both recalled fewer items than CONT and LLD. Group differences emerged when valence ratings were considered: at immediate and delayed recall, positive and negative pictures were generally better-remembered than neutral pictures by CONT, aMCI, and LLD, but valence was not associated with recall in aMCI/D+. Follow-up analyses suggested that the perceived intensity of stimuli may explain the emotional enhancement effect in CONT, aMCI, and LLD.
Conclusions:Results support previous research suggesting that the neuropsychological profile of aMCI/D+ is different from that of aMCI and LLD. Although depressed and non-depressed individuals with aMCI recall comparable quantities of information, the quality of the recalled information differs significantly. On theoretical grounds, this suggests the existence of distinct neurobiological or neurofunctional manifestations in both groups. Practically, these differences may guide the development of personalized emotion-focused encoding strategies in cognitive training programs.