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Artikel ; Online: Predictors and outcomes of fluctuations in the clinical dementia rating scale.

Wilks, Hannah / Benzinger, Tammie L S / Schindler, Suzanne E / Cruchaga, Carlos / Morris, John C / Hassenstab, Jason

Alzheimer's & dementia : the journal of the Alzheimer's Association

2024 Band 20, Heft 3, Seite(n) 2080–2088

Abstract: Introduction: Reversion, or change in cognitive status from impaired to normal, is common in aging and dementia studies, but it remains unclear what factors predict reversion.: Methods: We investigated whether reverters, defined as those who revert ... ...

Abstract	Introduction: Reversion, or change in cognitive status from impaired to normal, is common in aging and dementia studies, but it remains unclear what factors predict reversion. Methods: We investigated whether reverters, defined as those who revert from a Clinical Dementia Rating® (CDR®) scale score of 0.5 to CDR 0) differed on cognition and biomarkers from unimpaired participants (always CDR 0) and impaired participants (converted to CDR > 0 and had no reversion events). Models evaluated relationships between biomarker status, apolipoprotein E (APOE) ε4 status, and cognition. Additional models described predictors of reversion and predictors of eventual progression to CDR > 0. Results: CDR reversion was associated with younger age, better cognition, and negative amyloid biomarker status. Reverters that eventually progressed to CDR > 0 had more visits, were older, and were more likely to have an APOE ε4 allele. Discussion: CDR reversion occupies a transitional phase in disease progression between cognitive normality and overt dementia. Reverters may be ideal candidates for secondary prevention Alzheimer's disease (AD) trials. Highlights: Reverters had more longitudinal cognitive decline than those who remained cognitively normal. Predictors of reversion: younger age, better cognition, and negative amyloid biomarker status. Reverting from CDR 0.5 to 0 is a risk factor for future conversion to CDR > 0. CDR reversion may be a transitional phase in Alzheimer's Disease progression. CDR reverters may be ideal for Alzheimer's disease secondary prevention trials.
Mesh-Begriff(e)	Humans ; Alzheimer Disease/diagnosis ; Alzheimer Disease/genetics ; Alzheimer Disease/psychology ; Cognitive Dysfunction/diagnosis ; Cognitive Dysfunction/genetics ; Cognitive Dysfunction/psychology ; Cognition ; Mental Status and Dementia Tests ; Biomarkers ; Disease Progression
Chemische Substanzen	Biomarkers
Sprache	Englisch
Erscheinungsdatum	2024-01-15
Erscheinungsland	United States
Dokumenttyp	Journal Article
ZDB-ID	2211627-8
ISSN	1552-5279 ; 1552-5260
ISSN (online)	1552-5279
ISSN	1552-5260
DOI	10.1002/alz.13679
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: The Value of Neuroimaging in Dementia Diagnosis.

Raji, Cyrus A / Benzinger, Tammie L S

Continuum (Minneapolis, Minn.)

2022 Band 28, Heft 3, Seite(n) 800–821

Abstract: Purpose of review: This article discusses neuroimaging in dementia diagnosis, with a focus on new applications of MRI and positron emission tomography (PET).: Recent findings: Although the historical use of MRI in dementia diagnosis has been ... ...

Abstract	Purpose of review: This article discusses neuroimaging in dementia diagnosis, with a focus on new applications of MRI and positron emission tomography (PET). Recent findings: Although the historical use of MRI in dementia diagnosis has been supportive to exclude structural etiologies, recent innovations allow for quantification of atrophy patterns that improve sensitivity for supporting the diagnosis of dementia causes. Neuronuclear approaches allow for localization of specific amyloid and tau neuropathology on PET and are available for clinical use, in addition to dopamine transporter scans in dementia with Lewy bodies and metabolic studies with fludeoxyglucose PET (FDG-PET). Summary: Using computerized software programs for MRI analysis and cross-sectional and longitudinal evaluations of hippocampal, ventricular, and lobar volumes improves sensitivity in support of the diagnosis of Alzheimer disease and frontotemporal dementia. MRI protocol requirements for such quantification are three-dimensional T1-weighted volumetric imaging protocols, which may need to be specifically requested. Fluid-attenuated inversion recovery (FLAIR) and 3.0T susceptibility-weighted imaging (SWI) sequences are useful for the detection of white matter hyperintensities as well as microhemorrhages in vascular dementia and cerebral amyloid angiopathy. PET studies for amyloid and/or tau pathology can add additional specificity to the diagnosis but currently remain largely inaccessible outside of research settings because of prohibitive cost constraints in most of the world. Dopamine transporter PET scans can help identify Lewy body dementia and are thus of potential clinical value.
Mesh-Begriff(e)	Alzheimer Disease/diagnostic imaging ; Cross-Sectional Studies ; Dopamine Plasma Membrane Transport Proteins ; Humans ; Lewy Body Disease/diagnostic imaging ; Magnetic Resonance Imaging/methods ; Neuroimaging ; Positron-Emission Tomography
Chemische Substanzen	Dopamine Plasma Membrane Transport Proteins
Sprache	Englisch
Erscheinungsdatum	2022-06-08
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Review
ISSN	1538-6899
ISSN (online)	1538-6899
DOI	10.1212/CON.0000000000001133
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Beyond the

Raji, Cyrus A / Benzinger, Tammie L S

AJR. American journal of roentgenology

2020 Band 216, Heft 5, Seite(n) 1170

Mesh-Begriff(e)	Brain/diagnostic imaging ; Humans ; Longevity ; Magnetic Resonance Imaging
Sprache	Englisch
Erscheinungsdatum	2020-10-28
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Comment
ZDB-ID	82076-3
ISSN	1546-3141 ; 0361-803X ; 0092-5381
ISSN (online)	1546-3141
ISSN	0361-803X ; 0092-5381
DOI	10.2214/AJR.20.24985
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel: Analysing heterogeneity in Alzheimer's Disease using multimodal normative modelling on ATN biomarkers.

Kumar, Sayantan / Earnest, Thomas / Yang, Braden / Kothapalli, Deydeep / Benzinger, Tammie L S / Gordon, Brian A / Payne, Philip / Sotiras, Aristeidis

bioRxiv : the preprint server for biology

2024

Abstract: Background and objectives: Previous approaches pursuing normative modelling for analyzing heterogeneity in Alzheimer's Disease (AD) have relied on a single neuroimaging modality. However, AD is a multi-faceted disorder, with each modality providing ... ...

Abstract	Background and objectives: Previous approaches pursuing normative modelling for analyzing heterogeneity in Alzheimer's Disease (AD) have relied on a single neuroimaging modality. However, AD is a multi-faceted disorder, with each modality providing unique and complementary info about AD. In this study, we used a deep-learning based multimodal normative model to assess the heterogeneity in regional brain patterns for ATN (amyloid-tau-neurodegeneration) biomarkers. Methods: We selected discovery (n = 665) and replication (n = 430) cohorts with simultaneous availability of ATN biomarkers: Florbetapir amyloid, Flortaucipir tau and T1-weighted MRI (magnetic resonance imaging) imaging. A multimodal variational autoencoder (conditioned on age and sex) was used as a normative model to learn the multimodal regional brain patterns of a cognitively unimpaired (CU) control group. The trained model was applied on individuals on the ADS (AD Spectrum) to estimate their deviations (Z-scores) from the normative distribution, resulting in a Z-score regional deviation map per ADS individual per modality. Regions with Z-scores < -1.96 for MRI and Z-scores > 1.96 for amyloid and tau were labelled as outliers. Hamming distance was used to quantify the dissimilarity between individual based on their outlier deviations across each modality. We also calculated a disease severity index (DSI) for each ADS individual which was estimated by averaging the deviations across all outlier regions corresponding to each modality. Results: ADS individuals with moderate or severe dementia showed higher proportion of regional outliers for each modality as well as more dissimilarity in modality-specific regional outlier patterns compared to ADS individuals with early or mild dementia. DSI was associated with the progressive stages of dementia, (ii) showed significant associations with neuropsychological composite scores and (iii) related to the longitudinal risk of CDR progression. Findings were reproducible in both discovery and replication cohorts. Discussion: Our is the first study to examine the heterogeneity in AD through the lens of multiple neuroimaging modalities (ATN), based on distinct or overlapping patterns of regional outlier deviations. Regional MRI and tau outliers were more heterogenous than regional amyloid outliers. DSI has the potential to be an individual patient metric of neurodegeneration that can help in clinical decision making and monitoring patient response for anti-amyloid treatments.
Sprache	Englisch
Erscheinungsdatum	2024-04-04
Erscheinungsland	United States
Dokumenttyp	Preprint
DOI	10.1101/2023.08.15.553412
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel: Edge Density Imaging Identifies White Matter Biomarkers of Late-Life Obesity and Cognition.

Wang, Maxwell Bond / Rahmani, Farzaneh / Benzinger, Tammie L S / Raji, Cyrus

Aging and disease

2022

Abstract: Alzheimer disease (AD) and obesity are related to disruptions in the white matter (WM) connectome. We examined the link between the WM connectome and obesity and AD through edge-density imaging/index (EDI), a tractography-based method that characterizes ... ...

Abstract	Alzheimer disease (AD) and obesity are related to disruptions in the white matter (WM) connectome. We examined the link between the WM connectome and obesity and AD through edge-density imaging/index (EDI), a tractography-based method that characterizes the anatomical embedding of tractography connections. A total of 60 participants, 30 known to convert from normal cognition or mild-cognitive impairment to AD within a minimum of 24 months of follow up, were selected from the Alzheimer disease Neuroimaging Initiative (ADNI). Diffusion-weighted MR images from the baseline scans were used to extract fractional anisotropy (FA) and EDI maps that were subsequently averaged using deterministic WM tractography based on the Desikan-Killiany atlas. Multiple linear and logistic regression analysis were used to identify the weighted sum of tract-specific FA or EDI indices that maximized correlation to body-mass-index (BMI) or conversion to AD. Participants from the Open Access Series of Imaging Studies (OASIS) were used as an independent validation for the BMI findings. The edge-density rich, periventricular, commissural and projection fibers were among the most important WM tracts linking BMI to FA as well as to EDI. WM fibers that contributed significantly to the regression model related to BMI overlapped with those that predicted conversion; specifically in the frontopontine, corticostriatal, and optic radiation pathways. These results were replicated by testing the tract-specific coefficients found using ADNI in the OASIS-4 dataset. WM mapping with EDI enables identification of an abnormal connectome implicated in both obesity and conversion to AD.
Sprache	Englisch
Erscheinungsdatum	2022-12-16
Erscheinungsland	United States
Dokumenttyp	Journal Article
ZDB-ID	2625789-0
ISSN	2152-5250
ISSN	2152-5250
DOI	10.14336/AD.2022.1210
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel: The Spatial Patterns and Determinants of Cerebrospinal Fluid Circulation in the Human Brain.

Nazeri, Arash / Dehkharghanian, Taher / Lindsay, Kevin E / LaMontagne, Pamela / Shimony, Joshua S / Benzinger, Tammie L S / Sotiras, Aristeidis

bioRxiv : the preprint server for biology

2023

Abstract: The circulation of cerebrospinal fluid (CSF) is essential for maintaining brain homeostasis and clearance, and impairments in its flow can lead to various brain disorders. Recent studies have shown that CSF circulation can be interrogated using low b- ... ...

Abstract	The circulation of cerebrospinal fluid (CSF) is essential for maintaining brain homeostasis and clearance, and impairments in its flow can lead to various brain disorders. Recent studies have shown that CSF circulation can be interrogated using low b-value diffusion magnetic resonance imaging (
Sprache	Englisch
Erscheinungsdatum	2023-08-15
Erscheinungsland	United States
Dokumenttyp	Preprint
DOI	10.1101/2023.08.13.553149
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Metabolite Study and Structural Authentication for the First-in-Human Use Sphingosine-1-phosphate Receptor 1 Radiotracer.

Qiu, Lin / Jiang, Hao / Cho, Kevin / Yu, Yanbo / Jones, Lynne A / Huang, Tianyu / Perlmutter, Joel S / Gropler, Robert J / Brier, Matthew R / Patti, Gary J / Benzinger, Tammie L S / Tu, Zhude

ACS chemical neuroscience

2024 Band 15, Heft 9, Seite(n) 1882–1892

Abstract: The sphingosine-1-phosphate receptor 1 (S1PR1) radiotracer [ ...

Abstract	The sphingosine-1-phosphate receptor 1 (S1PR1) radiotracer [
Mesh-Begriff(e)	Animals ; Humans ; Positron-Emission Tomography/methods ; Rats ; Brain/metabolism ; Brain/diagnostic imaging ; Radiopharmaceuticals/pharmacokinetics ; Male ; Sphingosine-1-Phosphate Receptors/metabolism ; Rats, Sprague-Dawley ; Fluorine Radioisotopes ; Carbon Radioisotopes
Chemische Substanzen	Radiopharmaceuticals ; Sphingosine-1-Phosphate Receptors ; Fluorine Radioisotopes ; Carbon Radioisotopes
Sprache	Englisch
Erscheinungsdatum	2024-04-18
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	1948-7193
ISSN (online)	1948-7193
DOI	10.1021/acschemneuro.4c00077
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Increased cognitive effort costs in healthy aging and preclinical Alzheimer's disease.

Aschenbrenner, Andrew J / Crawford, Jennifer L / Peelle, Jonathan E / Fagan, Anne M / Benzinger, Tammie L S / Morris, John C / Hassenstab, Jason / Braver, Todd S

Psychology and aging

2023 Band 38, Heft 5, Seite(n) 428–442

Abstract: Life-long engagement in cognitively demanding activities may mitigate against declines in cognitive ability observed in healthy or pathological aging. However, the "mental costs" associated with completing cognitive tasks also increase with age and may ... ...

Abstract	Life-long engagement in cognitively demanding activities may mitigate against declines in cognitive ability observed in healthy or pathological aging. However, the "mental costs" associated with completing cognitive tasks also increase with age and may be partly attributed to increases in preclinical levels of Alzheimer's disease (AD) pathology, specifically amyloid. We test whether cognitive effort costs increase in a domain-general manner among older adults, and further, whether such age-related increases in cognitive effort costs are associated with working memory (WM) capacity or amyloid burden, a signature pathology of AD. In two experiments, we administered a behavioral measure of cognitive effort costs (cognitive effort discounting) to a sample of older adults recruited from online sources (Experiment 1) or from ongoing longitudinal studies of aging and dementia (Experiment 2). Experiment 1 compared age-related differences in cognitive effort costs across two domains, WM and speech comprehension. Experiment 2 compared cognitive effort costs between a group of participants who were rated positive for amyloid relative to those with no evidence of amyloid. Results showed age-related increases in cognitive effort costs were evident in both domains. Cost estimates were highly correlated between the WM and speech comprehension tasks but did not correlate with WM capacity. In addition, older adults who were amyloid positive had higher cognitive effort costs than those who were amyloid negative. Cognitive effort costs may index a domain-general trait that consistently increases in aging. Differences in cognitive effort costs associated with amyloid burden suggest a potential neurobiological mechanism for age-related differences. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
Mesh-Begriff(e)	Humans ; Aged ; Alzheimer Disease/psychology ; Aging ; Healthy Aging ; Memory, Short-Term ; Cognition
Sprache	Englisch
Erscheinungsdatum	2023-04-17
Erscheinungsland	United States
Dokumenttyp	Journal Article
ZDB-ID	635596-1
ISSN	1939-1498 ; 0882-7974
ISSN (online)	1939-1498
ISSN	0882-7974
DOI	10.1037/pag0000742
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Importance of CSF-based Aβ clearance with age in humans increases with declining efficacy of blood-brain barrier/proteolytic pathways.

Elbert, Donald L / Patterson, Bruce W / Lucey, Brendan P / Benzinger, Tammie L S / Bateman, Randall J

Communications biology

2022 Band 5, Heft 1, Seite(n) 98

Abstract: The kinetics of amyloid beta turnover within human brain is still poorly understood. We previously found a dramatic decline in the turnover of Aβ peptides in normal aging. It was not known if brain interstitial fluid/cerebrospinal fluid (ISF/CSF) fluid ... ...

Abstract	The kinetics of amyloid beta turnover within human brain is still poorly understood. We previously found a dramatic decline in the turnover of Aβ peptides in normal aging. It was not known if brain interstitial fluid/cerebrospinal fluid (ISF/CSF) fluid exchange, CSF turnover, blood-brain barrier function or proteolysis were affected by aging or the presence of β amyloid plaques. Here, we describe a non-steady state physiological model developed to decouple CSF fluid transport from other processes. Kinetic parameters were estimated using: (1) MRI-derived brain volumes, (2) stable isotope labeling kinetics (SILK) of amyloid-β peptide (Aβ), and (3) lumbar CSF Aβ concentration during SILK. Here we show that changes in blood-brain barrier transport and/or proteolysis were largely responsible for the age-related decline in Aβ turnover rates. CSF-based clearance declined modestly in normal aging but became increasingly important due to the slowing of other processes. The magnitude of CSF-based clearance was also lower than that due to blood-brain barrier function plus proteolysis. These results suggest important roles for blood-brain barrier transport and proteolytic degradation of Aβ in the development Alzheimer's Disease in humans.
Mesh-Begriff(e)	Aging/cerebrospinal fluid ; Amyloid beta-Peptides/cerebrospinal fluid ; Amyloid beta-Peptides/genetics ; Blood-Brain Barrier/physiology ; Humans ; Kinetics ; Models, Biological ; Mutation ; Proteolysis
Chemische Substanzen	Amyloid beta-Peptides
Sprache	Englisch
Erscheinungsdatum	2022-01-27
Erscheinungsland	England
Dokumenttyp	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	2399-3642
ISSN (online)	2399-3642
DOI	10.1038/s42003-022-03037-0
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Pick a PACC: Comparing domain-specific and general cognitive composites in Alzheimer disease research.

McKay, Nicole S / Millar, Peter R / Nicosia, Jessica / Aschenbrenner, Andrew J / Gordon, Brian A / Benzinger, Tammie L S / Cruchaga, Carolos C / Schindler, Suzanne E / Morris, John C / Hassenstab, Jason

Neuropsychology

2024

Abstract: Objective: We aimed to illustrate how complex cognitive data can be used to create domain-specific and general cognitive composites relevant to Alzheimer disease research.: Method: Using equipercentile equating, we combined data from the Charles F. ... ...

Abstract	Objective: We aimed to illustrate how complex cognitive data can be used to create domain-specific and general cognitive composites relevant to Alzheimer disease research. Method: Using equipercentile equating, we combined data from the Charles F. and Joanne Knight Alzheimer Disease Research Center that spanned multiple iterations of the Uniform Data Set. Exploratory factor analyses revealed four domain-specific composites representing episodic memory, semantic memory, working memory, and attention/processing speed. The previously defined preclinical Alzheimer disease cognitive composite (PACC) and a novel alternative, the Knight-PACC, were also computed alongside a global composite comprising all available tests. These three composites allowed us to compare the usefulness of domain and general composites in the context of predicting common Alzheimer disease biomarkers. Results: General composites slightly outperformed domain-specific metrics in predicting imaging-derived amyloid, tau, and neurodegeneration burden. Power analyses revealed that the global, Knight-PACC, and attention and processing speed composites would require the smallest sample sizes to detect cognitive change in a clinical trial, while the Alzheimer Disease Cooperative Study-PACC required two to three times as many participants. Conclusions: Analyses of cognition with the Knight-PACC and our domain-specific composites offer researchers flexibility by providing validated outcome assessments that can equate across test versions to answer a wide range of questions regarding cognitive decline in normal aging and neurodegenerative disease. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
Sprache	Englisch
Erscheinungsdatum	2024-04-11
Erscheinungsland	United States
Dokumenttyp	Journal Article
ZDB-ID	1042412-x
ISSN	1931-1559 ; 0894-4105
ISSN (online)	1931-1559
ISSN	0894-4105
DOI	10.1037/neu0000949
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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