Visual cognition in non-amnestic Alzheimer's disease: Relations to tau, amyloid, and cortical atrophy

Deepti Putcha; Michael Brickhouse; Alexandra Touroutoglou; Jessica A Collins; Megan Quimby; Bonnie Wong; Mark Eldaief; Aaron Schultz; Georges El Fakhri; Keith Johnson; Bradford C Dickerson; Scott M McGinnis

doi:10.1016/j.nicl.2019.101889

Visual cognition in non-amnestic Alzheimer's disease: Relations to tau, amyloid, and cortical atrophy

Neuroimage Clin. 2019:23:101889. doi: 10.1016/j.nicl.2019.101889. Epub 2019 Jun 4.

Affiliations

¹ Frontotemporal Disorders Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. Electronic address: dputcha@mgh.harvard.edu.
² Frontotemporal Disorders Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
³ Frontotemporal Disorders Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
⁴ Alzheimer's Disease Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
⁵ Gordon Center for Medical Imaging, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
⁶ Alzheimer's Disease Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; Gordon Center for Medical Imaging, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
⁷ Frontotemporal Disorders Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; Alzheimer's Disease Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.

Abstract

Heterogeneity within the Alzheimer's disease (AD) syndromic spectrum is typically classified in a domain-specific manner (e.g., language vs. visual cognitive function). The central aim of this study was to investigate whether impairment in visual cognitive tasks thought to be subserved by posterior cortical dysfunction in non-amnestic AD presentations is associated with tau, amyloid, or neurodegeneration in those regions using ¹⁸F-AV-1451 and ¹¹C-PiB positron emission tomography (PET) and magnetic resonance imaging (MRI). Sixteen amyloid-positive patients who met criteria for either Posterior Cortical Atrophy (PCA; n = 10) or logopenic variant Primary Progressive Aphasia (lvPPA; n = 6) were studied. All participants underwent a structured clinical assessment, neuropsychological battery, structural MRI, amyloid PET, and tau PET. The neuropsychological battery included two visual cognitive tests: VOSP Number Location and Benton Facial Recognition. Surface-based whole-cortical general linear models were used to first explore the similarities and differences between these biomarkers in the two patient groups, and then to assess their regional associations with visual cognitive test performance. The results show that these two variants of AD have both dissociable and overlapping areas of tau and atrophy, but amyloid is distributed with a stereotyped localization in both variants. Performance on both visual cognitive tests were associated with tau and atrophy in the right lateral and medial occipital association cortex, superior parietal cortex, and posterior ventral occipitotemporal cortex. No cortical associations were observed with amyloid PET. We further demonstrate that cortical atrophy has a partially mediating effect on the association between tau pathology and visual cognitive task performance. Our findings show that non-amnestic variants of AD have partially dissociable spatial patterns of tau and atrophy that localize as expected based on symptoms, but similar patterns of amyloid. Further, we demonstrate that impairments of visual cognitive dysfunction are strongly associated with tau in visual cortical regions and mediated in part by atrophy.

Keywords: Alzheimer's disease; Amyloid imaging; Brain atrophy; Tau imaging; Visual function.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Alzheimer Disease* / diagnostic imaging
Alzheimer Disease* / metabolism
Alzheimer Disease* / pathology
Alzheimer Disease* / physiopathology
Amyloid beta-Peptides / metabolism*
Aphasia, Primary Progressive* / diagnostic imaging
Aphasia, Primary Progressive* / metabolism
Aphasia, Primary Progressive* / pathology
Aphasia, Primary Progressive* / physiopathology
Atrophy / pathology
Cerebral Cortex* / diagnostic imaging
Cerebral Cortex* / metabolism
Cerebral Cortex* / pathology
Cerebral Cortex* / physiopathology
Facial Recognition / physiology
Female
Humans
Magnetic Resonance Imaging
Male
Middle Aged
Pattern Recognition, Visual / physiology*
Positron-Emission Tomography
tau Proteins / metabolism*

Substances

Amyloid beta-Peptides
tau Proteins

Grants and funding

P41 EB022544/EB/NIBIB NIH HHS/United States