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Mol Psychiatry. 2018 Aug 16. doi: 10.1038/s41380-018-0214-2. [Epub ahead of print]

Association of anxiety with subcortical amyloidosis in cognitively normal older adults.

Author information

1
Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA.
2
Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA.
3
Department of Neurology, Cliniques Universitaires Saint-Luc, Institute of Neurosciences, Université Catholique de Louvain, Brussels, Belgium.
4
Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, 02115, USA.
5
Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
6
Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
7
Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
8
Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA. njdonovan@bwh.harvard.edu.
9
Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA. njdonovan@bwh.harvard.edu.
10
Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA. njdonovan@bwh.harvard.edu.
11
Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA. njdonovan@bwh.harvard.edu.

Abstract

Late-life anxiety has been associated with increased progression from normal cognition to amnestic MCI, suggesting that anxiety may be a neuropsychiatric symptom of Alzheimer's disease (AD) pathological changes and a possible marker of anatomical progression in preclinical AD. This study examined whether cortical or subcortical amyloidosis, indicating earlier or later stages of preclinical AD, was associated with greater self-reported anxiety among 118 cognitively normal volunteers, aged 65-90 years, and whether this association was stronger in APOEε4 carriers. Participants underwent Pittsburgh Compound B Positron Emission Tomography (PiB-PET) to assess fibrillar amyloid-β burden in cortical and subcortical regions, and measurement of anxiety using the Hospital Anxiety and Depression Scale-anxiety subscale. Higher PiB-PET measures in the subcortex (striatum, amygdala, and thalamus), but not in the cortex, were associated with greater anxiety, adjusting for demographics, cognition, and depression. Findings were similar using a cortico-striatal staging system and continuous PET measurements. Anxiety was highest in APOEε4 carriers with subcortical amyloidosis. This work supports in vivo staging of amyloid-β deposition in both cortical and subcortical regions as a promising approach to the study of neuropsychiatric symptoms such as anxiety in cognitively normal older individuals. Elevated anxiety symptoms in combination with high-risk biological factors such as APOEε4 and subcortical amyloid-β may identify participants closest to MCI for secondary prevention trials.

PMID:
30116029
DOI:
10.1038/s41380-018-0214-2

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