Jennifer R Gatchel1, Nancy J Donovan2, Joseph J Locascio3, J Alex Becker4, Dorene M Rentz5, Reisa A Sperling6, Keith A Johnson7, Gad A Marshall6. 1. Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA; Division of Geriatric Psychiatry, McLean Hospital, Harvard Medical School, Belmont, MA. Electronic address: jgatchel@partners.org. 2. Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA; Center of Alzheimer Research and Treatment, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA. 3. Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA. 4. Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA. 5. Center of Alzheimer Research and Treatment, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA. 6. Center of Alzheimer Research and Treatment, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA. 7. Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA; Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
Abstract
OBJECTIVES: Apathy is among the earliest and most pervasive neuropsychiatric symptoms in prodromal and mild Alzheimer disease (AD) dementia that correlates with functional impairment and disease progression. We investigated the association of apathy with regional 18F-fluorodeoxyglucose (FDG) metabolism in cognitively normal, mild cognitive impairment, and AD dementia subjects from the Alzheimer's Disease Neuroimaging Initiative database. DESIGN: Cross-sectional and longitudinal studies. SETTING: 57 North American research sites. PARTICIPANTS: 402 community dwelling elders. MEASUREMENTS: Apathy was assessed using the Neuropsychiatric Inventory Questionnaire. Baseline FDG metabolism in five regions implicated in the neurobiology of apathy and AD was investigated in relationship to apathy at baseline (cross-sectional general linear model) and longitudinally (mixed random/fixed effect model). Covariates included age, sex, diagnosis, apolipoprotein E genotype, premorbid intelligence, cognition, and antidepressant use. RESULTS: Cross-sectional analysis revealed that posterior cingulate hypometabolism, diagnosis, male sex, and antidepressant use were associated with higher apathy scores. Longitudinal analysis revealed that the interaction of supramarginal hypometabolism and time, posterior cingulate hypometabolism, and antidepressant use were associated with higher apathy scores across time; only supramarginal hypometabolism was positively related to rate of increase of apathy. CONCLUSIONS: Results support an association of apathy with hypometabolism in parietal regions commonly affected in early stages of AD, rather than medial frontal regions implicated in the neurobiology of apathy in later stages. Further work is needed to substantiate whether this localization is specific to apathy rather than to disease stage, and to investigate the potential role of AD proteinopathies in the pathogenesis of apathy.
OBJECTIVES: Apathy is among the earliest and most pervasive neuropsychiatric symptoms in prodromal and mild Alzheimer disease (AD) dementia that correlates with functional impairment and disease progression. We investigated the association of apathy with regional 18F-fluorodeoxyglucose (FDG) metabolism in cognitively normal, mild cognitive impairment, and AD dementia subjects from the Alzheimer's Disease Neuroimaging Initiative database. DESIGN: Cross-sectional and longitudinal studies. SETTING: 57 North American research sites. PARTICIPANTS: 402 community dwelling elders. MEASUREMENTS: Apathy was assessed using the Neuropsychiatric Inventory Questionnaire. Baseline FDG metabolism in five regions implicated in the neurobiology of apathy and AD was investigated in relationship to apathy at baseline (cross-sectional general linear model) and longitudinally (mixed random/fixed effect model). Covariates included age, sex, diagnosis, apolipoprotein E genotype, premorbid intelligence, cognition, and antidepressant use. RESULTS: Cross-sectional analysis revealed that posterior cingulate hypometabolism, diagnosis, male sex, and antidepressant use were associated with higher apathy scores. Longitudinal analysis revealed that the interaction of supramarginal hypometabolism and time, posterior cingulate hypometabolism, and antidepressant use were associated with higher apathy scores across time; only supramarginal hypometabolism was positively related to rate of increase of apathy. CONCLUSIONS: Results support an association of apathy with hypometabolism in parietal regions commonly affected in early stages of AD, rather than medial frontal regions implicated in the neurobiology of apathy in later stages. Further work is needed to substantiate whether this localization is specific to apathy rather than to disease stage, and to investigate the potential role of AD proteinopathies in the pathogenesis of apathy.
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