2019
DOI: 10.1101/791657
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White matter hyperintensities and neuropsychiatric symptoms in Alzheimer’s disease and mild cognitive impairment

Abstract: Background and Purpose: Neuropsychiatric symptoms (NPS) are frequently encountered in patients with Alzheimer's disease (AD). Focal grey matter atrophy has been linked to NPS development. Cerebrovascular disease can cause focal lesions and is common among AD patients. As cerebrovascular disease can be detected on MRI as white matter hyperintensities (WMH), this study evaluated WMH burden in mild cognitive impairment (MCI), AD and normal controls and determined their relationship with NPS. Methods: NPS were ass… Show more

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Cited by 4 publications
(10 citation statements)
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References 41 publications
(46 reference statements)
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“…In PD, the neural correlates of apathy have been structurally and functionally linked to a broad range of regions modulated by dopamine like the ventral striatum, prefrontal cortex, anterior cingulate, bilateral inferior frontoparietal, nucleus accumbens, and ventral tegmental area [127][128][129][130][131][132][133]. Likewise in AD/MCI, Guercio et al [20] found apathy was associated with decreased inferior temporal and increased anterior cingulate thickness in MCI whilst other studies found atrophy of the bilateral anterior cingulate, left prefrontal, left caudate nucleus, and bilateral putamen regions were associated with apathy in AD [39,[134][135][136]. These ndings in AD/MCI have been corroborated in some functional imaging studies that observed a relationship between apathy and hypometabolism in the anterior cingulate cortex and medial prefrontal cortex [137][138][139] in addition to being linked with increased neuro brillary tangles in the anterior cingulate cortex [140].…”
Section: Discussionmentioning
confidence: 99%
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“…In PD, the neural correlates of apathy have been structurally and functionally linked to a broad range of regions modulated by dopamine like the ventral striatum, prefrontal cortex, anterior cingulate, bilateral inferior frontoparietal, nucleus accumbens, and ventral tegmental area [127][128][129][130][131][132][133]. Likewise in AD/MCI, Guercio et al [20] found apathy was associated with decreased inferior temporal and increased anterior cingulate thickness in MCI whilst other studies found atrophy of the bilateral anterior cingulate, left prefrontal, left caudate nucleus, and bilateral putamen regions were associated with apathy in AD [39,[134][135][136]. These ndings in AD/MCI have been corroborated in some functional imaging studies that observed a relationship between apathy and hypometabolism in the anterior cingulate cortex and medial prefrontal cortex [137][138][139] in addition to being linked with increased neuro brillary tangles in the anterior cingulate cortex [140].…”
Section: Discussionmentioning
confidence: 99%
“…A main strength of our study was the inclusion of multiple neurodegenerative disease groups, especially participants with ALS, FTD, and PD. Prior research examining atrophy and/or WMH correlates of NPS have mostly focused on AD/MCI and CVD [31,32,39], occasionally on PD and FTD [163,165], and rarely on ALS [143]. Thus, our study provides an opportunity to investigate these associations across several disease groups.…”
Section: Limitations and Strengthsmentioning
confidence: 99%
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“…The image processing and WMH segmentation pipelines used in the present study have been developed and validated for use in multi-center and multi-scanner studies of aging and neurodegenerative disease populations and have been previously used in such applications (Anor et al, 2021; Dadar et al, 2020c, 2018e; Misquitta et al, 2020; Sanford et al, 2019). In addition to initial validation of the performance of the pipeline against gold standard manual segmentations which showed excellent agreement, manual quality control was performed to ensure the quality of the raw images, registrations, and segmentations.…”
Section: Discussionmentioning
confidence: 99%
“…In terms of clinical symptoms, WMHs are associated with increased cognitive deficits (particularly in executive function and higher-order cognitive functions, such as planning, organizing, and monitoring behaviour) and neurobehavioral and psychiatric problems (e.g., depression, irritability, apathy, anxiety, and agitation), and gait difficulties (Anor et al, 2021; Arvanitakis et al, 2016; Baezner et al, 2008; Dadar et al, 2021, 2020a, 2020c; Kapasi et al, 2017; Misquitta et al, 2020; Srikanth et al, 2010; Teodorczuk et al, 2007; Van Der Flier et al, 2018). Of particular relevance, WMH are known to increase the risk of dementia for the same level of neurodegenerative pathology (Anor et al, 2021; Arvanitakis et al, 2016; Baezner et al, 2008; Dadar et al, 2021, 2020a, 2020c; Kapasi et al, 2017; Misquitta et al, 2020; Srikanth et al, 2010; Teodorczuk et al, 2007; Van Der Flier et al, 2018).…”
Section: Introductionmentioning
confidence: 99%