Voxel-based morphometry findings in Alzheimer's disease: neuropsychiatric symptoms and disability correlations – preliminary results

Vasconcelos, Luciano de Gois; Jackowski, Andrea Parolin; Oliveira, Maira Okada de; Flor, Yoná Mayara Ribeiro; Bueno, Orlando Francisco Amodeo; Brucki, Sônia Maria Dozzi

doi:10.1590/s1807-59322011000600021

Cited by 19 publications

(23 citation statements)

References 35 publications

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“…[29] Two studies employing structural magnetic resonance imaging (MRI) showed an association between IADL impairment and medial frontal and temporoparietal atrophy. [30,31] Of note, the FDG-PET results presented in our study were not corrected for partial volume effects and were therefore likely influenced by underlying atrophy. As such, our imaging results might be more representative of overall neurodegeneration, as seen with structural MRI, rather than regional synaptic dysfunction, which is more specific to FDG-PET.…”

Section: Discussionmentioning

confidence: 96%

Regional Fluorodeoxyglucose Metabolism and Instrumental Activities of Daily Living across the Alzheimer's Disease Spectrum

Roy

Pepin

Philiossaint

et al. 2014

JAD

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Background Impairment in instrumental activities of daily living (IADL) begins as individuals with amnestic mild cognitive impairment (MCI) transition to Alzheimer's disease (AD) dementia. IADL impairment in AD dementia has been associated with inferior parietal, inferior temporal, and superior occipital hypometabolism using 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET). Objective To investigate the relationship between regional FDG metabolism and IADL in clinically normal (CN) elderly, MCI, and mild AD dementia subjects cross-sectionally and longitudinally. Methods One hundred and four CN, 203 MCI, and 95 AD dementia subjects from the Alzheimer's Disease Neuroimaging Initiative underwent clinical assessments every 6 to 12 months for up to three years and baseline FDG PET. The subjective, informant-based Functional Activities Questionnaire was used to assess IADL. General linear models and mixed effects models were used, covarying for demographics, cogniton, and behavior. Results The cross-sectional analysis revealed middle frontal and orbitofrontal hypometabolism were significantly associated with greater IADL impairment. Additionally, the interaction of diagnosis with posterior cingulate and with parahippocampal hypometabolism showed a greater decline in IADL performance as metabolism decreased for the AD dementia relative to the MCI group, and the MCI group relative to the CN group. The longitudinal analysis showed that baseline middle frontal and posterior cingulate hypometabolism were significantly associated with greater rate of increase in IADL impairment over time. Conclusion These results suggest that regional synaptic dysfunction, including the Alzheimer-typical medial parietal and less typical frontal regions, relates to daily functioning decline at baseline and over time across the early AD spectrum.

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Section: Discussionmentioning

confidence: 96%

Regional Fluorodeoxyglucose Metabolism and Instrumental Activities of Daily Living across the Alzheimer's Disease Spectrum

Roy

Pepin

Philiossaint

et al. 2014

JAD

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“…Previous, smaller, cross-sectional, MRI studies showed an association between IADL impairment and temporal atrophy in mild AD dementia[9,10] similar to our results indicating an association with reduced inferior temporal cortical thickness signifying atrophy, driven by the mild AD dementia group; one of the other studies also showed an association with parietal and medial frontal atrophy[9]. Another cross-sectional study employing FDG PET showed an association between IADL impairment and inferior temporal hypometabolism in mild to moderate AD dementia similar to our regional results; it also showed an association with inferior parietal and superior occipital hypometabolism[11].…”

Section: Discussionmentioning

confidence: 97%

“…Other studies have attempted to more closely localize IADL impairment in the brain. Cross-sectional MRI studies showed an association between IADL impairment and temporoparietal and medial frontal atrophy in mild AD dementia[9,10], while cross-sectional functional imaging studies showed an association with inferior temporal, inferior parietal, and superior occipital hypometabolism in mild to moderate AD dementia[11], and medial frontal, dorsolateral prefrontal, lateral superior parietal, and occipital hypoperfusion in mild AD dementia[12]. …”

Section: Introductionmentioning

confidence: 99%

Regional Cortical Thinning and Cerebrospinal Biomarkers Predict Worsening Daily Functioning Across the Alzheimer's Disease Spectrum

Marshall

Lorius

Locascio

et al. 2014

JAD

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Background Impairment in instrumental activities of daily living (IADL) heralds the transition from mild cognitive impairment (MCI) to dementia and is a major source of burden for both the patient and caregiver. Objective To investigate the relationship between IADL and regional cortical thinning and cerebrospinal fluid (CSF) Alzheimer disease (AD) biomarkers cross-sectionally and longitudinally in clinically normal (CN) elderly, MCI, and mild AD dementia subjects. Methods Two hundred and twenty nine CN, 395 MCI, and 188 AD dementia subjects participating in the Alzheimer's Disease Neuroimaging Initiative underwent baseline magnetic resonance imaging, baseline lumbar puncture, and clinical assessments, including the Functional Activities Questionnaire used to measure IADL, every 6 to 12 months up to 3 years. General linear regression and mixed effects models were employed. Results IADL impairment was associated with the interactions between lower inferior temporal cortical thickness and diagnosis (p<0.0001), greater lateral occipital cortical thickness and diagnosis (p<0.0001), and greater amyloid-beta 1-42 (Aβ1-42) and diagnosis (p=0.0002) at baseline (driven by AD dementia). Lower baseline supramarginal (p=0.02) and inferior temporal (p=0.05) cortical thickness, lower Aβ1-42 (p<0.0001), and greater total tau (t-tau) (p=0.02) were associated with greater rate of IADL impairment over time. Conclusions Temporal atrophy is associated with IADL impairment in mild AD dementia at baseline, while baseline parietal and temporal atrophy, lower CSF Aβ1-42, and greater t-tau predict worsening IADL impairment over time across the AD spectrum. These results emphasize the importance of assessing IADL at the stage of MCI and even at the transition from CN to MCI.

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“…Once this study is replicated in the general population, these questions can serve as a useful, straight-forward screening tool for early AD. IADL impairment in early AD has been associated with greater amyloid burden and various markers of neurodegeneration [23–30]. In order to better validate the utility of the sensitive questions identified here, future studies could explore their association with AD biomarkers.…”

Section: Discussionmentioning

confidence: 99%

Everyday Cognition Scale Items that Best Discriminate Between and Predict Progression From Clinically Normal to Mild Cognitive Impairment

Marshall¹,

Zoller²,

Kelly³

et al. 2014

CAR

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Background Impairment in instrumental activities of daily living (IADL) starts as individuals with amnestic mild cognitive impairment (MCI) transition to Alzheimer’s disease (AD) dementia. However, most IADL scales have not shown IADL alterations in clinically normal (CN) elderly. The objective of this study was to determine which of the IADL-related Everyday Cognition (ECog) scale items are most sensitive for detection of early functional changes. Methods We assessed 290 CN and 495 MCI participants from the Alzheimer’s Disease Neuroimaging Initiative. We performed logistic regression analyses predicting the probability of CN vs. MCI diagnosis using only the 17 participant-based and 17 informant-based ECog items related to IADL. We then performed Cox regression analyses to predict progression from CN to MCI. All analyses were adjusted for demographic characteristics. Results We found that worse performance on “remembering a few shopping items” (participant and informant-based p<0.0001), “remembering appointments” (participant and informant-based p<0.0001), “developing a schedule in advance of anticipated events” (participant-based p=0.007), “balancing checkbook” (participant-based p=0.02), and “keeping mail and papers organized” (informant-based p=0.002) best discriminated MCI from CN. We found that worse performance on “keeping mail and papers organized” (participant-based Hazard Ratio (HR)=2.27, p=0.07) marginally predicted greater hazard of progressing from CN to MCI. Conclusions Our results indicate that a few simple questions targeting early functional changes, addressed either to the individual or informant, can effectively distinguish between CN elderly and individuals with MCI. Additionally, one of the above questions related to organization suggested which CN individuals are likely to progress to MCI.

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Voxel-based morphometry findings in Alzheimer's disease: neuropsychiatric symptoms and disability correlations – preliminary results

Cited by 19 publications

References 35 publications

Regional Fluorodeoxyglucose Metabolism and Instrumental Activities of Daily Living across the Alzheimer's Disease Spectrum

Regional Fluorodeoxyglucose Metabolism and Instrumental Activities of Daily Living across the Alzheimer's Disease Spectrum

Regional Cortical Thinning and Cerebrospinal Biomarkers Predict Worsening Daily Functioning Across the Alzheimer's Disease Spectrum

Everyday Cognition Scale Items that Best Discriminate Between and Predict Progression From Clinically Normal to Mild Cognitive Impairment

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