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Article ; Online: Neuroimaging in Dementia.

Risacher, Shannon L / Apostolova, Liana G

Continuum (Minneapolis, Minn.)

2023 Volume 29, Issue 1, Page(s) 219–254

Abstract: Objective: Neurodegenerative diseases are significant health concerns with regard to morbidity and social and economic hardship around the world. This review describes the state of the field of neuroimaging measures as biomarkers for detection and ... ...

Abstract	Objective: Neurodegenerative diseases are significant health concerns with regard to morbidity and social and economic hardship around the world. This review describes the state of the field of neuroimaging measures as biomarkers for detection and diagnosis of both slowly progressing and rapidly progressing neurodegenerative diseases, specifically Alzheimer disease, vascular cognitive impairment, dementia with Lewy bodies or Parkinson disease dementia, frontotemporal lobar degeneration spectrum disorders, and prion-related diseases. It briefly discusses findings in these diseases in studies using MRI and metabolic and molecular-based imaging (eg, positron emission tomography [PET] and single-photon emission computerized tomography [SPECT]). Latest developments: Neuroimaging studies with MRI and PET have demonstrated differential patterns of brain atrophy and hypometabolism in different neurodegenerative disorders, which can be useful in differential diagnoses. Advanced MRI sequences, such as diffusion-based imaging, and functional MRI (fMRI) provide important information about underlying biological changes in dementia and new directions for development of novel measures for future clinical use. Finally, advancements in molecular imaging allow clinicians and researchers to visualize dementia-related proteinopathies and neurotransmitter levels. Essential points: Diagnosis of neurodegenerative diseases is primarily based on symptomatology, although the development of in vivo neuroimaging and fluid biomarkers is changing the scope of clinical diagnosis, as well as the research into these devastating diseases. This article will help inform the reader about the current state of neuroimaging in neurodegenerative diseases, as well as how these tools might be used for differential diagnoses.
MeSH term(s)	Humans ; Parkinson Disease ; Neuroimaging/methods ; Alzheimer Disease/diagnosis ; Positron-Emission Tomography/methods ; Neurodegenerative Diseases ; Magnetic Resonance Imaging ; Frontotemporal Dementia/diagnosis ; Biomarkers
Chemical Substances	Biomarkers
Language	English
Publishing date	2023-02-16
Publishing country	United States
Document type	Review ; Journal Article
ISSN	1538-6899
ISSN (online)	1538-6899
DOI	10.1212/CON.0000000000001248
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Article ; Online: Atypical Alzheimer Disease Variants.

Polsinelli, Angelina J / Apostolova, Liana G

Continuum (Minneapolis, Minn.)

2022 Volume 28, Issue 3, Page(s) 676–701

Abstract: Purpose of review: This article discusses the clinical, neuroimaging, and biomarker profiles of sporadic atypical Alzheimer disease (AD) variants, including early-onset AD, posterior cortical atrophy, logopenic variant primary progressive aphasia, ... ...

Abstract	Purpose of review: This article discusses the clinical, neuroimaging, and biomarker profiles of sporadic atypical Alzheimer disease (AD) variants, including early-onset AD, posterior cortical atrophy, logopenic variant primary progressive aphasia, dysexecutive variant and behavioral variant AD, and corticobasal syndrome. Recent findings: Significant advances are being made in the recognition and characterization of the syndromically diverse AD variants. These variants are identified by the predominant cognitive and clinical features: early-onset amnestic syndrome, aphasia, visuospatial impairments, dysexecutive and behavioral disturbance, or motor symptoms. Although understanding of regional susceptibility to disease remains in its infancy, visualizing amyloid and tau pathology in vivo and CSF examination of amyloid-β and tau proteins are particularly useful in atypical AD, which can be otherwise prone to misdiagnosis. Large-scale research efforts, such as LEADS (the Longitudinal Early-Onset Alzheimer Disease Study), are currently ongoing and will continue to shed light on our understanding of these diverse presentations. Summary: Understanding the clinical, neuroimaging, and biomarker profiles of the heterogeneous group of atypical AD syndromes improves diagnostic accuracy in patients who are at increased risk of misdiagnosis. Earlier accurate identification facilitates access to important interventions, social services and disability assistance, and crucial patient and family education.
MeSH term(s)	Alzheimer Disease/diagnosis ; Alzheimer Disease/pathology ; Aphasia ; Atrophy ; Biomarkers ; Humans ; Neuroimaging ; tau Proteins/metabolism
Chemical Substances	Biomarkers ; tau Proteins
Language	English
Publishing date	2022-06-08
Publishing country	United States
Document type	Journal Article ; Review
ISSN	1538-6899
ISSN (online)	1538-6899
DOI	10.1212/CON.0000000000001082
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Article ; Online: Alzheimer disease: A quantitative trait approach to GWAS pays dividends.

Apostolova, Liana G

Nature reviews. Neurology

2017 Volume 13, Issue 6, Page(s) 321–322

MeSH term(s)	Alzheimer Disease/genetics ; Endophenotypes ; Genome-Wide Association Study/methods ; Humans ; Quantitative Trait Loci/genetics
Language	English
Publishing date	2017-04-28
Publishing country	England
Document type	News
ZDB-ID	2491514-2
ISSN	1759-4766 ; 1759-4758
ISSN (online)	1759-4766
ISSN	1759-4758
DOI	10.1038/nrneurol.2017.61
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Article: Examining the role of repeated test exposure over 12 months across ADNI protocols.

Hammers, Dustin B / Duff, Kevin / Apostolova, Liana G

Alzheimer's & dementia (Amsterdam, Netherlands)

2022 Volume 14, Issue 1, Page(s) e12289

Abstract: ... ...

Abstract	Objective
Language	English
Publishing date	2022-02-24
Publishing country	United States
Document type	Journal Article
ZDB-ID	2832898-X
ISSN	2352-8729
ISSN	2352-8729
DOI	10.1002/dad2.12289
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Article ; Online: Validation of and Demographically Adjusted Normative Data for the Learning Ratio Derived from the RAVLT in Robustly Intact Older Adults.

Hammers, Dustin B / Spencer, Robert J / Apostolova, Liana G

Archives of clinical neuropsychology : the official journal of the National Academy of Neuropsychologists

2022 Volume 37, Issue 5, Page(s) 981–993

Abstract: Background: The learning ratio (LR) is a novel learning slope score that was developed to identify learning more accurately by considering the proportion of information learned after the first trial of a multi-trial learning task. Specifically, LR is ... ...

Abstract	Background: The learning ratio (LR) is a novel learning slope score that was developed to identify learning more accurately by considering the proportion of information learned after the first trial of a multi-trial learning task. Specifically, LR is the number of items learned after trial one divided by the number of items yet to be learned. Although research on LR has been promising, convergent validation, clinical characterization, and demographic norming of this LR metric are warranted to understand its clinical utility when derived from the Rey Auditory Verbal Learning Test (RAVLT). Method: Data from 674 robustly cognitively intact older participants from the Alzheimer's Disease Neuroimaging Initiative (aged 54- 89) were used to calculate the LR metric. Comparison of LR's relationship with standard memory measures was undertaken relative to other traditional learning slope metrics. In addition, retest reliability at 6, 12, and 24 months was examined, and demographically adjusted normative comparisons were developed. Results: Lower LR scores were associated with poorer performances on memory measures, and LR scores outperformed traditional learning slope calculations across all analyses. Retest reliability exceeded acceptability thresholds across time, and demographically adjusted normative equations suggested better performance for cognitively intact participants than those with mild cognitive impairment. Conclusions: These results suggest that this LR score possesses sound retest reliability and can better reflect learning capacity than traditional learning slope calculations. With the added development and validation of regression-based normative comparisons, these findings support the use of the RAVLT LR as a clinical tool to inform clinical decision-making and treatment.
MeSH term(s)	Aged ; Cognitive Dysfunction/diagnosis ; Cognitive Dysfunction/psychology ; Humans ; Memory and Learning Tests ; Neuropsychological Tests ; Reproducibility of Results ; Verbal Learning
Language	English
Publishing date	2022-02-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	632972-x
ISSN	1873-5843 ; 0887-6177
ISSN (online)	1873-5843
ISSN	0887-6177
DOI	10.1093/arclin/acac002
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Article ; Online: Alzheimer Disease.

Apostolova, Liana G

Continuum (Minneapolis, Minn.)

2015 Volume 22, Issue 2 Dementia, Page(s) 419–434

Abstract: Purpose of review: This article discusses the recent advances in the diagnosis and treatment of Alzheimer disease (AD).: Recent findings: In recent years, significant advances have been made in the fields of genetics, neuroimaging, clinical diagnosis, ...

Abstract	Purpose of review: This article discusses the recent advances in the diagnosis and treatment of Alzheimer disease (AD). Recent findings: In recent years, significant advances have been made in the fields of genetics, neuroimaging, clinical diagnosis, and staging of AD. One of the most important recent advances in AD is our ability to visualize amyloid pathology in the living human brain. The newly revised criteria for diagnosis of AD dementia embrace the use for biomarkers as supportive evidence for the underlying pathology. Guidelines for the responsible use of amyloid positron emission tomography (PET) have been developed, and the clinical and economic implications of amyloid PET imaging are actively being explored. Summary: Our improved understanding of the clinical onset, progression, neuroimaging, pathologic features, genetics, and other risk factors for AD impacts the approaches to clinical diagnosis and future therapeutic interventions.
MeSH term(s)	Alzheimer Disease/diagnosis ; Alzheimer Disease/epidemiology ; Alzheimer Disease/therapy ; Cognition Disorders/etiology ; Disease Progression ; Humans ; Neuropsychological Tests ; Psychiatric Status Rating Scales
Language	English
Publishing date	2015-10-15
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ISSN	1538-6899
ISSN (online)	1538-6899
DOI	10.1212/CON.0000000000000307
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Article ; Online: Assessing and validating reliable change across ADNI protocols.

Hammers, Dustin B / Kostadinova, Ralitsa / Unverzagt, Frederick W / Apostolova, Liana G

Journal of clinical and experimental neuropsychology

2022 Volume 44, Issue 2, Page(s) 85–102

Abstract: Objective: Reliable change methods can aid in determining whether changes in cognitive performance over time are meaningful. The current study sought to develop and cross-validate 12-month standardized regression-based (SRB) equations for the ... ...

Abstract	Objective: Reliable change methods can aid in determining whether changes in cognitive performance over time are meaningful. The current study sought to develop and cross-validate 12-month standardized regression-based (SRB) equations for the neuropsychological measures commonly administered in the Alzheimer's Disease Neuroimaging Initiative (ADNI) longitudinal study. Method: Prediction algorithms were developed using baseline score, retest interval, the presence/absence of a 6-month evaluation, age, education, sex, and ethnicity in two different samples ( Results: Minimal differences were seen between Observed 12-month and Predicted 12-month scores on most neuropsychological tests from ADNI, and when compared across samples the resultant Predicted 12-month scores were highly correlated. As a result, samples were combined and SRB prediction equations were successfully developed for each of the measures. Conclusions: Establishing cross-validation for these SRB prediction equations provides initial support of their use to detect meaningful change in the ADNI sample, and provides the basis for future research with clinical samples to evaluate potential clinical utility. While some caution should be considered for measuring true cognitive change over time - particularly in clinical samples - when using these prediction equations given the relatively lower coefficients of stability observed, use of these SRBs reflects an improvement over current practice in ADNI.
MeSH term(s)	Aged ; Alzheimer Disease/diagnostic imaging ; Humans ; Longitudinal Studies ; Neuroimaging/methods ; Neuropsychological Tests
Language	English
Publishing date	2022-07-04
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	605982-x
ISSN	1744-411X ; 0168-8634 ; 1380-3395
ISSN (online)	1744-411X
ISSN	0168-8634 ; 1380-3395
DOI	10.1080/13803395.2022.2082386
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Article ; Online: The relationship between learning slopes and Alzheimer's Disease biomarkers in cognitively unimpaired participants with and without subjective memory concerns.

Hammers, Dustin B / Pentchev, Julian V / Kim, Hee Jin / Spencer, Robert J / Apostolova, Liana G

Journal of clinical and experimental neuropsychology

2023 Volume 45, Issue 7, Page(s) 727–743

Abstract: Objective: Learning slopes represent serial acquisition of information during list-learning tasks. Although several calculations for learning slopes exist, the Learning Ratio (LR) has recently demonstrated the highest sensitivity toward changes in ... ...

Abstract	Objective: Learning slopes represent serial acquisition of information during list-learning tasks. Although several calculations for learning slopes exist, the Learning Ratio (LR) has recently demonstrated the highest sensitivity toward changes in cognition and Alzheimer's disease (AD) biomarkers. However, investigation of learning slopes in cognitively unimpaired individuals with subjective memory concerns (SMC) has been limited. The current study examines the association of learning slopes to SMC, and the role of SMC in the relationship between learning slopes and AD biomarkers in cognitively unimpaired individuals. Method: Data from 950 cognitively unimpaired participants from the Alzheimer's Disease Neuroimaging Initiative (aged 55 to 89) were used to calculate learning slope metrics. Learning slopes among those with and without SMC were compared with demographic correction, and the relationships of learning slopes with AD biomarkers of bilateral hippocampal volume and β-amyloid pathology were determined. Results: Learning slopes were consistently predictive of hippocampal atrophy and β-amyloid deposition. Results were heightened for LR relative to the other learning slopes. Additionally, interaction analyses revealed different associations between learning slopes and hippocampal volume as a function of SMC status. Conclusions: Learning slopes appear to be sensitive to SMC and AD biomarkers, with SMC status influencing the relationship in cognitively unimpaired participants. These findings advance our knowledge of SMC, and suggest that LR - in particular - can be an important tool for the detection of AD pathology in both SMC and in AD clinical trials.
MeSH term(s)	Humans ; Alzheimer Disease/diagnostic imaging ; Learning ; Biomarkers ; Cognition ; Data Interpretation, Statistical
Chemical Substances	Biomarkers
Language	English
Publishing date	2023-09-07
Publishing country	England
Document type	Journal Article
ZDB-ID	605982-x
ISSN	1744-411X ; 0168-8634 ; 1380-3395
ISSN (online)	1744-411X
ISSN	0168-8634 ; 1380-3395
DOI	10.1080/13803395.2023.2254444
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Article ; Online: Amyloid-related imaging abnormalities (ARIA): radiological, biological and clinical characteristics.

Hampel, Harald / Elhage, Aya / Cho, Min / Apostolova, Liana G / Nicoll, James A R / Atri, Alireza

Brain : a journal of neurology

2023 Volume 146, Issue 11, Page(s) 4414–4424

Abstract: Excess accumulation and aggregation of toxic soluble and insoluble amyloid-β species in the brain are a major hallmark of Alzheimer's disease. Randomized clinical trials show reduced brain amyloid-β deposits using monoclonal antibodies that target ... ...

Abstract	Excess accumulation and aggregation of toxic soluble and insoluble amyloid-β species in the brain are a major hallmark of Alzheimer's disease. Randomized clinical trials show reduced brain amyloid-β deposits using monoclonal antibodies that target amyloid-β and have identified MRI signal abnormalities called amyloid-related imaging abnormalities (ARIA) as possible spontaneous or treatment-related adverse events. This review provides a comprehensive state-of-the-art conceptual review of radiological features, clinical detection and classification challenges, pathophysiology, underlying biological mechanism(s) and risk factors/predictors associated with ARIA. We summarize the existing literature and current lines of evidence with ARIA-oedema/effusion (ARIA-E) and ARIA-haemosiderosis/microhaemorrhages (ARIA-H) seen across anti-amyloid clinical trials and therapeutic development. Both forms of ARIA may occur, often early, during anti-amyloid-β monoclonal antibody treatment. Across randomized controlled trials, most ARIA cases were asymptomatic. Symptomatic ARIA-E cases often occurred at higher doses and resolved within 3-4 months or upon treatment cessation. Apolipoprotein E haplotype and treatment dosage are major risk factors for ARIA-E and ARIA-H. Presence of any microhaemorrhage on baseline MRI increases the risk of ARIA. ARIA shares many clinical, biological and pathophysiological features with Alzheimer's disease and cerebral amyloid angiopathy. There is a great need to conceptually link the evident synergistic interplay associated with such underlying conditions to allow clinicians and researchers to further understand, deliberate and investigate on the combined effects of these multiple pathophysiological processes. Moreover, this review article aims to better assist clinicians in detection (either observed via symptoms or visually on MRI), management based on appropriate use recommendations, and general preparedness and awareness when ARIA are observed as well as researchers in the fundamental understanding of the various antibodies in development and their associated risks of ARIA. To facilitate ARIA detection in clinical trials and clinical practice, we recommend the implementation of standardized MRI protocols and rigorous reporting standards. With the availability of approved amyloid-β therapies in the clinic, standardized and rigorous clinical and radiological monitoring and management protocols are required to effectively detect, monitor, and manage ARIA in real-world clinical settings.
MeSH term(s)	Humans ; Alzheimer Disease/complications ; Antibodies, Monoclonal, Humanized/therapeutic use ; Amyloid beta-Peptides/metabolism ; Brain/metabolism ; Amyloid ; Amyloidogenic Proteins
Chemical Substances	Antibodies, Monoclonal, Humanized ; Amyloid beta-Peptides ; Amyloid ; Amyloidogenic Proteins
Language	English
Publishing date	2023-06-09
Publishing country	England
Document type	Review ; Journal Article
ZDB-ID	80072-7
ISSN	1460-2156 ; 0006-8950
ISSN (online)	1460-2156
ISSN	0006-8950
DOI	10.1093/brain/awad188
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Article ; Online: Alzheimer disease: 'generation next' in Alzheimer disease genetic studies.

Apostolova, Liana G

Nature reviews. Neurology

2013 Volume 9, Issue 8, Page(s) 422–423

MeSH term(s)	Aged ; Aged, 80 and over ; Alzheimer Disease/epidemiology ; Alzheimer Disease/genetics ; Endophenotypes ; Genetic Testing ; Hippocampus/pathology ; Humans ; Risk Factors
Language	English
Publishing date	2013-07-16
Publishing country	England
Document type	News
ZDB-ID	2491514-2
ISSN	1759-4766 ; 1759-4758
ISSN (online)	1759-4766
ISSN	1759-4758
DOI	10.1038/nrneurol.2013.133
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