Simona Sacuiu1, Philip S Insel2, Susanne Mueller3, Duygu Tosun3, Niklas Mattsson1, Clifford R Jack4, Charles DeCarli5, Ronald Petersen6, Paul S Aisen7, Michael W Weiner3, R Scott Mackin8. 1. Center for Imaging of Neurodegenerative Diseases, Veterans Affairs Medical Center, San Francisco, CA; Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA; Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Sweden. 2. Center for Imaging of Neurodegenerative Diseases, Veterans Affairs Medical Center, San Francisco, CA. 3. Center for Imaging of Neurodegenerative Diseases, Veterans Affairs Medical Center, San Francisco, CA; Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA. 4. Department of Radiology, Mayo Clinic, Rochester, MN. 5. Department of Neurology and Center for Neuroscience, University of California at Davis, Sacramento, CA. 6. Mayo Alzheimer's Disease Research Center and Mayo Clinic College of Medicine, Rochester, MN. 7. Department of Neurosciences, University of California, San Diego, CA. 8. Center for Imaging of Neurodegenerative Diseases, Veterans Affairs Medical Center, San Francisco, CA; Department of Psychiatry, University of California San Francisco, San Francisco, CA. Electronic address: scottm@lppi.ucsf.edu.
Abstract
OBJECTIVE: Investigate the association of chronic depressive symptomatology (chrDS) with cortical atrophy rates and conversion to Alzheimer dementia (AD) over 3 years in mild cognitive impairment (MCI). METHODS: In a multicenter, clinic-based study, MCI elderly participants were selected from the Alzheimer's Disease Neuroimaging Initiative repository, based on availability of both serial structural magnetic resonance imaging and chrDS endorsed on three depression-related items from the Neuropsychiatric Inventory Questionnaire (chrDS N = 32 or no depressive symptoms N = 62) throughout follow-up. Clinical and laboratory investigations were performed every 6 months during the first 2 years and yearly thereafter (median follow-up: 3 years; interquartile range: 1.5-4.0 years). Cortical atrophy rates in 16 predefined frontotemporoparietal regions affected in major depression and AD and the rate of incident AD at follow-up. RESULTS: ChrDS in a single domain amnestic MCI sample were associated with accelerated cortical atrophy in the frontal lobe and anterior cingulate but not with atrophy rates in temporomedial or other AD-affected regions. During follow-up, 38 participants (42.7%) developed AD. Participants with chrDS had 60% shorter conversion time to AD than those without depressive symptoms. This association remained significant in survival models adjusted for temporomedial atrophy rates and showed the same trend in models adjusted for frontal cortical atrophy rate, which all increased the risk of AD. CONCLUSION: Our results suggest that chrDS associated with progressive atrophy of frontal regions may represent an additional risk factor for conversion to dementia in MCI as opposite to representing typical prodromal AD symptomatology. Published by Elsevier Inc.
OBJECTIVE: Investigate the association of chronic depressive symptomatology (chrDS) with cortical atrophy rates and conversion to Alzheimer dementia (AD) over 3 years in mild cognitive impairment (MCI). METHODS: In a multicenter, clinic-based study, MCI elderly participants were selected from the Alzheimer's Disease Neuroimaging Initiative repository, based on availability of both serial structural magnetic resonance imaging and chrDS endorsed on three depression-related items from the Neuropsychiatric Inventory Questionnaire (chrDS N = 32 or no depressive symptoms N = 62) throughout follow-up. Clinical and laboratory investigations were performed every 6 months during the first 2 years and yearly thereafter (median follow-up: 3 years; interquartile range: 1.5-4.0 years). Cortical atrophy rates in 16 predefined frontotemporoparietal regions affected in major depression and AD and the rate of incident AD at follow-up. RESULTS: ChrDS in a single domain amnestic MCI sample were associated with accelerated cortical atrophy in the frontal lobe and anterior cingulate but not with atrophy rates in temporomedial or other AD-affected regions. During follow-up, 38 participants (42.7%) developed AD. Participants with chrDS had 60% shorter conversion time to AD than those without depressive symptoms. This association remained significant in survival models adjusted for temporomedial atrophy rates and showed the same trend in models adjusted for frontal cortical atrophy rate, which all increased the risk of AD. CONCLUSION: Our results suggest that chrDS associated with progressive atrophy of frontal regions may represent an additional risk factor for conversion to dementia in MCI as opposite to representing typical prodromal AD symptomatology. Published by Elsevier Inc.
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