Quantitative validation of a visual rating scale for frontal atrophy: associations with clinical status, APOE e4, CSF biomarkers and cognition

Ferreira, Daniel; Cavallin, Lena; Granberg, Tobias; Lindberg, Olof; Aguilar, Carlos; Mecocci, Patrizia; Vellas, Bruno; Tsolaki, Magda; Kłoszewska, Iwona; Soininen, Hilkka; Lovestone, Simon; Simmons, Andrew; Wahlund, Lars Olof; Westman, Eric

doi:10.1007/s00330-015-4101-9

Cited by 43 publications

(54 citation statements)

References 60 publications

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“…L.C. has participated as single rater in seven previous independent studies, achieving intrarater agreement of weighted kappa values between 0.88 and 0.94 for MTA, of 0.70 for GCA-F, and of 0.72 for PA [6,25,27,28,29,30,31,32]. Good interrater agreement has previously been demonstrated for L.C.…”

Section: Methodsmentioning

confidence: 91%

“…Good interrater agreement has previously been demonstrated for L.C. in comparison with a second rater [25,33], manual tracings from another experienced radiologist [30], and multivariate classification from automated morphometric methods [29]. …”

Section: Methodsmentioning

confidence: 99%

“…Since the distribution of MRI and CT was homogeneous across diagnostic groups (table 1) and similar agreement on visual ratings has been obtained when comparing MRI and 64-detector row CT [23], all MRI and CT images were combined and included in the analysis. Images were visually rated using scales of MTA, frontal lobe atrophy (GCA-F), and posterior atrophy (PA), as detailed elsewhere [24,25,26]. In these three scales, a score of 0 denotes no atrophy, whereas scores from 1 to 3 (4 in MTA) indicate an increasing degree of atrophy (see online suppl.…”

Section: Methodsmentioning

confidence: 99%

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Electroencephalography Is a Good Complement to Currently Established Dementia Biomarkers

Ferreira

Jelić

Cavallin

et al. 2016

Dement Geriatr Cogn Disord

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Background/Aims: Dementia biomarkers that are accessible and easily applicable in nonspecialized clinical settings are urgently needed. Quantitative electroencephalography (qEEG) is a good candidate, and the statistical pattern recognition (SPR) method has recently provided promising results. We tested the diagnostic value of qEEG-SPR in comparison to cognition, structural imaging, and cerebrospinal fluid (CSF) biomarkers. Methods: A total of 511 individuals were recruited from the multicenter NORD EEG study [141 healthy controls, 64 subjective cognitive decline, 124 mild cognitive impairment, 135 Alzheimer's disease (AD), 15 dementia with Lewy bodies/Parkinson's disease with dementia (DLB/PDD), 32 other dementias]. The EEG data were recorded in a standardized way. Structural imaging data were visually rated using scales of atrophy in the medial temporal, frontal, and posterior cortex. Results: qEEG-SPR outperformed structural imaging, cognition, and CSF biomarkers in DLB/PDD diagnosis, outperformed structural imaging in AD diagnosis, and improved the differential diagnosis of AD. In addition, qEEG-SPR allowed differentiation of two clinically different AD subtypes. Conclusion: Adding qEEG to the diagnostic workup substantially increases the detection of AD pathology even in pre-dementia stages and improves differential diagnosis. EEG could serve as a good complement to currently established dementia biomarkers since it is cheap, noninvasive, and extensively applied outside academic centers.

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Section: Methodsmentioning

confidence: 91%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Electroencephalography Is a Good Complement to Currently Established Dementia Biomarkers

Ferreira

Jelić

Cavallin

et al. 2016

Dement Geriatr Cogn Disord

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“…The BV/CSF index correlated with functions beyond episodic memory, suggesting that the index reflects the effect of processes leading to both global brain atrophy and disease-specific regional atrophy. Although regional atrophy in the medial temporal lobe is the main finding in AD and causes memory impairment [44], atrophy in other brain regions such as the frontal lobe and posterior cortex is also frequently reported [45,46]. Therefore, measurements that account for atrophy in brain regions other than the medial temporal lobe are important in AD [41].…”

Section: Discussionmentioning

confidence: 99%

Measuring Global Brain Atrophy with the Brain Volume/Cerebrospinal Fluid Index: Normative Values, Cut-Offs and Clinical Associations

et al. 2015

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Background: Global brain atrophy is present in normal aging and different neurodegenerative disorders such as Alzheimer's disease (AD) and is becoming widely used to monitor disease progression. Summary: The brain volume/cerebrospinal fluid index (BV/CSF index) is validated in this study as a measurement of global brain atrophy. We tested the ability of the BV/CSF index to detect global brain atrophy, investigated the influence of confounders, provided normative values and cut-offs for mild, moderate and severe brain atrophy, and studied associations with different outcome variables. A total of 1,009 individuals were included [324 healthy controls, 408 patients with mild cognitive impairment (MCI) and 277 patients with AD]. Magnetic resonance images were segmented using FreeSurfer, and the BV/CSF index was calculated and studied both cross-sectionally and longitudinally (1-year follow-up). Both AD patients and MCI patients who progressed to AD showed greater global brain atrophy compared to stable MCI patients and controls. Atrophy was associated with older age, larger intracranial volume, less education and presence of the ApoE ε4 allele. Significant correlations were found with clinical variables, CSF biomarkers and several cognitive tests. Key Messages: The BV/CSF index may be useful for staging individuals according to the degree of global brain atrophy, and for monitoring disease progression. It also shows potential for predicting clinical changes and for being used in the clinical routine.

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“…Cortical reconstruction was performed as described in detail elsewhere [39]. Quality control of the output was carried out.…”

Section: Methodsmentioning

confidence: 99%

Dual tracer tau PET imaging reveals different molecular targets for 11C-THK5351 and 11C-PBB3 in the Alzheimer brain

Chiotis

Stenkrona

Almkvist

et al. 2018

Eur J Nucl Med Mol Imaging

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PurposeSeveral tau PET tracers have been developed, but it remains unclear whether they bind to the same molecular target on the heterogeneous tau pathology. In this study we evaluated the binding of two chemically different tau-specific PET tracers (11C-THK5351 and 11C-PBB3) in a head-to-head, in vivo, multimodal design.MethodsNine patients with a diagnosis of mild cognitive impairment or probable Alzheimer’s disease and cerebrospinal fluid biomarker evidence supportive of the presence of Alzheimer’s disease brain pathology were recruited after thorough clinical assessment. All patients underwent imaging with the tau-specific PET tracers 11C-THK5351 and 11C-PBB3 on the same day, as well as imaging with the amyloid-beta-specific tracer 11C-AZD2184, a T1-MRI sequence, and neuropsychological assessment.ResultsThe load and regional distribution of binding differed between 11C-THK5351 and 11C-PBB3 with no statistically significant regional correlations observed between the tracers. The binding pattern of 11C-PBB3, but not that of 11C-THK5351, in the temporal lobe resembled that of 11C-AZD2184, with strong correlations detected between 11C-PBB3 and 11C-AZD2184 in the temporal and occipital lobes. Global cognition correlated more closely with 11C-THK5351 than with 11C-PBB3 binding. Similarly, cerebrospinal fluid tau measures and entorhinal cortex thickness were more closely correlated with 11C-THK5351 than with 11C-PBB3 binding.ConclusionThis research suggests different molecular targets for these tracers; while 11C-PBB3 appeared to preferentially bind to tau deposits with a close spatial relationship to amyloid-beta, the binding pattern of 11C-THK5351 fitted the expected distribution of tau pathology in Alzheimer’s disease better and was more closely related to downstream disease markers.Electronic supplementary materialThe online version of this article (10.1007/s00259-018-4012-5) contains supplementary material, which is available to authorized users.

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Quantitative validation of a visual rating scale for frontal atrophy: associations with clinical status, APOE e4, CSF biomarkers and cognition

Cited by 43 publications

References 60 publications

Electroencephalography Is a Good Complement to Currently Established Dementia Biomarkers

Electroencephalography Is a Good Complement to Currently Established Dementia Biomarkers

Measuring Global Brain Atrophy with the Brain Volume/Cerebrospinal Fluid Index: Normative Values, Cut-Offs and Clinical Associations

Dual tracer tau PET imaging reveals different molecular targets for 11C-THK5351 and 11C-PBB3 in the Alzheimer brain

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