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Investigating the clinico-anatomical dissociation in the behavioral variant of Alzheimer disease

Singleton, Ellen H. ; Pijnenburg, Yolande A.L. ; Sudre, Carole H. ; Groot, Colin ; Kochova, Elena ; Barkhof, Frederik ; La Joie, Renaud ; Rosen, Howard J. ; Seeley, William W. and Miller, Bruce , et al. (2020) In Alzheimer's Research and Therapy 12(1).
Abstract

Background: We previously found temporoparietal-predominant atrophy patterns in the behavioral variant of Alzheimer’s disease (bvAD), with relative sparing of frontal regions. Here, we aimed to understand the clinico-anatomical dissociation in bvAD based on alternative neuroimaging markers. Methods: We retrospectively included 150 participants, including 29 bvAD, 28 “typical” amnestic-predominant AD (tAD), 28 behavioral variant of frontotemporal dementia (bvFTD), and 65 cognitively normal participants. Patients with bvAD were compared with other diagnostic groups on glucose metabolism and metabolic connectivity measured by [18F]FDG-PET, and on subcortical gray matter and white matter hyperintensity (WMH) volumes measured by... (More)

Background: We previously found temporoparietal-predominant atrophy patterns in the behavioral variant of Alzheimer’s disease (bvAD), with relative sparing of frontal regions. Here, we aimed to understand the clinico-anatomical dissociation in bvAD based on alternative neuroimaging markers. Methods: We retrospectively included 150 participants, including 29 bvAD, 28 “typical” amnestic-predominant AD (tAD), 28 behavioral variant of frontotemporal dementia (bvFTD), and 65 cognitively normal participants. Patients with bvAD were compared with other diagnostic groups on glucose metabolism and metabolic connectivity measured by [18F]FDG-PET, and on subcortical gray matter and white matter hyperintensity (WMH) volumes measured by MRI. A receiver-operating-characteristic-analysis was performed to determine the neuroimaging measures with highest diagnostic accuracy. Results: bvAD and tAD showed predominant temporoparietal hypometabolism compared to controls, and did not differ in direct contrasts. However, overlaying statistical maps from contrasts between patients and controls revealed broader frontoinsular hypometabolism in bvAD than tAD, partially overlapping with bvFTD. bvAD showed greater anterior default mode network (DMN) involvement than tAD, mimicking bvFTD, and reduced connectivity of the posterior cingulate cortex with prefrontal regions. Analyses of WMH and subcortical volume showed closer resemblance of bvAD to tAD than to bvFTD, and larger amygdalar volumes in bvAD than tAD respectively. The top-3 discriminators for bvAD vs. bvFTD were FDG posterior-DMN-ratios (bvAD<bvFTD), MRI posterior-DMN-ratios (bvAD<bvFTD), MRI salience-network-ratios (bvAD>bvFTD, area under the curve [AUC] range 0.85–0.91, all p < 0.001). The top-3 for bvAD vs. tAD were amygdalar volume (bvAD>tAD), MRI anterior-DMN-ratios (bvAD<tAD), FDG anterior-DMN-ratios (bvAD<tAD, AUC range 0.71–0.84, all p < 0.05). Conclusions: Subtle frontoinsular hypometabolism and anterior DMN involvement may underlie the prominent behavioral phenotype in bvAD.

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publishing date
type
Contribution to journal
publication status
published
subject
keywords
Alzheimer’s disease, Behavior, Frontotemporal dementia, MRI, PET
in
Alzheimer's Research and Therapy
volume
12
issue
1
article number
148
publisher
BioMed Central (BMC)
external identifiers
  • pmid:33189136
  • scopus:85096022843
ISSN
1758-9193
DOI
10.1186/s13195-020-00717-z
language
English
LU publication?
yes
id
2fd30269-a2ff-410c-8ebc-378a98386a4d
date added to LUP
2020-11-24 12:35:37
date last changed
2025-03-07 03:02:20
@article{2fd30269-a2ff-410c-8ebc-378a98386a4d,
  abstract     = {{<p>Background: We previously found temporoparietal-predominant atrophy patterns in the behavioral variant of Alzheimer’s disease (bvAD), with relative sparing of frontal regions. Here, we aimed to understand the clinico-anatomical dissociation in bvAD based on alternative neuroimaging markers. Methods: We retrospectively included 150 participants, including 29 bvAD, 28 “typical” amnestic-predominant AD (tAD), 28 behavioral variant of frontotemporal dementia (bvFTD), and 65 cognitively normal participants. Patients with bvAD were compared with other diagnostic groups on glucose metabolism and metabolic connectivity measured by [<sup>18</sup>F]FDG-PET, and on subcortical gray matter and white matter hyperintensity (WMH) volumes measured by MRI. A receiver-operating-characteristic-analysis was performed to determine the neuroimaging measures with highest diagnostic accuracy. Results: bvAD and tAD showed predominant temporoparietal hypometabolism compared to controls, and did not differ in direct contrasts. However, overlaying statistical maps from contrasts between patients and controls revealed broader frontoinsular hypometabolism in bvAD than tAD, partially overlapping with bvFTD. bvAD showed greater anterior default mode network (DMN) involvement than tAD, mimicking bvFTD, and reduced connectivity of the posterior cingulate cortex with prefrontal regions. Analyses of WMH and subcortical volume showed closer resemblance of bvAD to tAD than to bvFTD, and larger amygdalar volumes in bvAD than tAD respectively. The top-3 discriminators for bvAD vs. bvFTD were FDG posterior-DMN-ratios (bvAD&lt;bvFTD), MRI posterior-DMN-ratios (bvAD&lt;bvFTD), MRI salience-network-ratios (bvAD&gt;bvFTD, area under the curve [AUC] range 0.85–0.91, all p &lt; 0.001). The top-3 for bvAD vs. tAD were amygdalar volume (bvAD&gt;tAD), MRI anterior-DMN-ratios (bvAD&lt;tAD), FDG anterior-DMN-ratios (bvAD&lt;tAD, AUC range 0.71–0.84, all p &lt; 0.05). Conclusions: Subtle frontoinsular hypometabolism and anterior DMN involvement may underlie the prominent behavioral phenotype in bvAD.</p>}},
  author       = {{Singleton, Ellen H. and Pijnenburg, Yolande A.L. and Sudre, Carole H. and Groot, Colin and Kochova, Elena and Barkhof, Frederik and La Joie, Renaud and Rosen, Howard J. and Seeley, William W. and Miller, Bruce and Cardoso, M. Jorge and Papma, Janne and Scheltens, Philip and Rabinovici, Gil D. and Ossenkoppele, Rik}},
  issn         = {{1758-9193}},
  keywords     = {{Alzheimer’s disease; Behavior; Frontotemporal dementia; MRI; PET}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{BioMed Central (BMC)}},
  series       = {{Alzheimer's Research and Therapy}},
  title        = {{Investigating the clinico-anatomical dissociation in the behavioral variant of Alzheimer disease}},
  url          = {{http://dx.doi.org/10.1186/s13195-020-00717-z}},
  doi          = {{10.1186/s13195-020-00717-z}},
  volume       = {{12}},
  year         = {{2020}},
}