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Article ; Online: Comparing neuropsychological, typical, and ADNI criteria for the diagnosis of mild cognitive impairment in Vietnam-era veterans.

Ly, Monica T / Adler, Jennifer / Ton Loy, Adan F / Edmonds, Emily C / Bondi, Mark W / Delano-Wood, Lisa

Journal of the International Neuropsychological Society : JINS

2024 , Page(s) 1–9

Abstract: Objective: Neuropsychological criteria for mild cognitive impairment (MCI) more accurately predict progression to Alzheimer's disease (AD) and are more strongly associated with AD biomarkers and neuroimaging profiles than ADNI criteria. However, ... ...

Abstract	Objective: Neuropsychological criteria for mild cognitive impairment (MCI) more accurately predict progression to Alzheimer's disease (AD) and are more strongly associated with AD biomarkers and neuroimaging profiles than ADNI criteria. However, research to date has been conducted in relatively healthy samples with few comorbidities. Given that history of traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD) are risk factors for AD and common in Veterans, we compared neuropsychological, typical (Petersen/Winblad), and ADNI criteria for MCI in Vietnam-era Veterans with histories of TBI or PTSD. Method: 267 Veterans (mean age = 69.8) from the DOD-ADNI study were evaluated for MCI using neuropsychological, typical, and ADNI criteria. Linear regressions adjusting for age and education assessed associations between MCI status and AD biomarker levels (cerebrospinal fluid [CSF] Results: Agreement between criteria was poor. Neuropsychological criteria identified more Veterans with MCI than typical or ADNI criteria, and were associated with higher CSF Conclusions: MCI diagnosis using sensitive neuropsychological criteria is more strongly associated with AD biomarkers than conventional diagnostic methods. MCI diagnostics in Veterans would benefit from incorporation of comprehensive neuropsychological methods and consideration of the impact of PTSD.
Language	English
Publishing date	2024-01-24
Publishing country	England
Document type	Journal Article
ZDB-ID	1230632-0
ISSN	1469-7661 ; 1355-6177
ISSN (online)	1469-7661
ISSN	1355-6177
DOI	10.1017/S135561772301144X
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Article ; Online: Data-driven classification of cognitively normal and mild cognitive impairment subtypes predicts progression in the NACC dataset.

Edmonds, Emily C / Thomas, Kelsey R / Rapcsak, Steven Z / Lindemer, Shannon L / Delano-Wood, Lisa / Salmon, David P / Bondi, Mark W

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

2024

Abstract: Introduction: Data-driven neuropsychological methods can identify mild cognitive impairment (MCI) subtypes with stronger associations to dementia risk factors than conventional diagnostic methods.: Methods: Cluster analysis used neuropsychological ... ...

Abstract	Introduction: Data-driven neuropsychological methods can identify mild cognitive impairment (MCI) subtypes with stronger associations to dementia risk factors than conventional diagnostic methods. Methods: Cluster analysis used neuropsychological data from participants without dementia (mean age = 71.6 years) in the National Alzheimer's Coordinating Center (NACC) Uniform Data Set (n = 26,255) and the "normal cognition" subsample (n = 16,005). Survival analyses examined MCI or dementia progression. Results: Five clusters were identified: "Optimal" cognitively normal (oCN; 13.2%), "Typical" CN (tCN; 28.0%), Amnestic MCI (aMCI; 25.3%), Mixed MCI-Mild (mMCI-Mild; 20.4%), and Mixed MCI-Severe (mMCI-Severe; 13.0%). Progression to dementia differed across clusters (oCN < tCN < aMCI < mMCI-Mild < mMCI-Severe). Cluster analysis identified more MCI cases than consensus diagnosis. In the "normal cognition" subsample, five clusters emerged: High-All Domains (High-All; 16.7%), Low-Attention/Working Memory (Low-WM; 22.1%), Low-Memory (36.3%), Amnestic MCI (16.7%), and Non-amnestic MCI (naMCI; 8.3%), with differing progression rates (High-All < Low-WM = Low-Memory < aMCI < naMCI). Discussion: Our data-driven methods outperformed consensus diagnosis by providing more precise information about progression risk and revealing heterogeneity in cognition and progression risk within the NACC "normal cognition" group.
Language	English
Publishing date	2024-04-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	2211627-8
ISSN	1552-5279 ; 1552-5260
ISSN (online)	1552-5279
ISSN	1552-5260
DOI	10.1002/alz.13793
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Article ; Online: News event memory in amnestic and non-amnestic MCI, heritable risk for dementia, and subjective memory complaints.

Asp, Isabel / Cawley-Bennett, Andrew T J / Frascino, Jennifer C / Golshan, Shahrokh / Bondi, Mark W / Smith, Christine N

Neuropsychologia

2024 Volume 199, Page(s) 108887

Abstract: Robust and sensitive clinical measures are needed for more accurate and earlier detection of Alzheimer's disease (AD), for staging preclinical AD, and for gauging the efficacy of treatments. Mild impairment on episodic memory tests is thought to indicate ...

Abstract	Robust and sensitive clinical measures are needed for more accurate and earlier detection of Alzheimer's disease (AD), for staging preclinical AD, and for gauging the efficacy of treatments. Mild impairment on episodic memory tests is thought to indicate a cognitive risk of developing AD and mild cognitive impairment (MCI), considered to be a transitional stage between normal aging and AD. Novel tests of semantic memory, such as memory for news events, are also impaired early on but have received little clinical attention even though they may provide a novel way to assess cognitive risk for AD. We examined memory for news events in older adults with normal cognition (NC, N = 34), amnestic MCI (aMCI, N = 27), or non-aMCI (N = 10) using the Retrograde Memory News Events Test (RM-NET). We asked if news event memory was sensitive to 1) aMCI and also non-aMCI, which has rarely been examined, 2) genetic risk for dementia (positive family history of any type of dementia, presence of an APOE-4 allele, or polygenic risk for AD), and 3) subjective memory functioning judgments about the past. We found that both MCI subgroups exhibited impaired RM-NET Lifespan accuracy scores together with temporally-limited retrograde amnesia. For the aMCI group amnesia extended back 45 years prior to testing, but not beyond that time frame. The extent of retrograde amnesia could not be reliably estimated in the small non-aMCI group. The effect sizes of having MCI on the RM-NET were medium for the non-aMCI group and large for the aMCI group, whereas the effect sizes of participant characteristics on RM-NET accuracy scores were small. For the combined MCI group (N = 37), news event memory was significantly related to positive family history of dementia but was not related to the more specific genetic markers of AD risk. For the NC group, news event memory was not related to any measure of genetic risk. Objective measures of past memory from the RM-NET were not related to subjective memory judgements about the present or the recent past in either group. By contrast, when individuals subjectively compared their present versus past memory abilities, there was a significant association between this judgment and objective measures of the past from the RM-NET (direct association for the NC group and inverse for the MCI group). The RM-NET holds significant promise for early identification of those with cognitive and genetic risk factors for AD and non-AD dementias.
Language	English
Publishing date	2024-04-15
Publishing country	England
Document type	Journal Article
ZDB-ID	207151-4
ISSN	1873-3514 ; 0028-3932
ISSN (online)	1873-3514
ISSN	0028-3932
DOI	10.1016/j.neuropsychologia.2024.108887
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Article ; Online: What's the cut-point?: a systematic investigation of tau PET thresholding methods.

Weigand, Alexandra J / Maass, Anne / Eglit, Graham L / Bondi, Mark W

Alzheimer's research & therapy

2022 Volume 14, Issue 1, Page(s) 49

Abstract: Background: Tau positron emission tomography (PET) is increasing in popularity for biomarker characterization of Alzheimer's disease (AD), and recent frameworks rely on tau PET cut-points to stage individuals along the AD continuum. Given the lack of ... ...

Abstract	Background: Tau positron emission tomography (PET) is increasing in popularity for biomarker characterization of Alzheimer's disease (AD), and recent frameworks rely on tau PET cut-points to stage individuals along the AD continuum. Given the lack of standardization in tau PET thresholding methods, this study sought to systematically canvass and characterize existing studies that have derived tau PET cut-points and then directly assess different methods of tau PET thresholding in terms of their concurrent validity. Methods: First, a literature search was conducted in PubMed to identify studies of AD and related clinical phenotypes that used the Flortaucipir (AV-1451) tau PET tracer to derive a binary cut-point for tau positivity. Of 540 articles screened and 47 full-texts reviewed, 23 cohort studies met inclusion criteria with a total of 6536 participants. Second, we derived and compared tau PET cut-points in a 2 × 2 × 2 design that systematically varied region (temporal meta-ROI and entorhinal cortex), analytic method (receiver operating characteristics and 2 standard deviations above comparison group), and criterion/comparison variable (amyloid-beta negative cognitively unimpaired or cognitively unimpaired only) using a sample of 453 older adults from the Alzheimer's Disease Neuroimaging Initiative. Results: For the systematic review, notable variability in sample characteristics, preprocessing methods, region of interest, and analytic approach were observed, which were accompanied by discrepancy in proposed tau PET cut points. The empirical follow-up indicated the cut-point derived based on 2 standard deviations above a either comparison group in either ROI best differentiated tau positive and negative groups on cerebrospinal fluid phosphorylated tau, Mini-Mental State Examination score, and delayed memory performance. Conclusions: Given the impact of discrepant thresholds on tau positivity rates, biomarker staging, and eligibility for future clinical treatment trials, recommendations are offered to select cut-point derivations based on the unique goals and priorities of different studies.
MeSH term(s)	Aged ; Alzheimer Disease/genetics ; Amyloid beta-Peptides ; Cognitive Dysfunction ; Humans ; Neuroimaging ; Positron-Emission Tomography/methods ; tau Proteins/cerebrospinal fluid
Chemical Substances	Amyloid beta-Peptides ; tau Proteins
Language	English
Publishing date	2022-04-05
Publishing country	England
Document type	Journal Article ; Review ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural
ZDB-ID	2506521-X
ISSN	1758-9193 ; 1758-9193
ISSN (online)	1758-9193
ISSN	1758-9193
DOI	10.1186/s13195-022-00986-w
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Article ; Online: Editorial Introduction to the Special Issue on Neuropsychological Assessment in Aging.

Summers, Mathew J / Bondi, Mark W

Neuropsychology review

2017 Volume 27, Issue 4, Page(s) 303–304

MeSH term(s)	Aging/psychology ; Cognitive Dysfunction/diagnosis ; Humans ; Neurodegenerative Diseases/diagnosis ; Neuropsychological Tests
Language	English
Publishing date	2017-11-18
Publishing country	United States
Document type	Editorial ; Introductory Journal Article
ZDB-ID	1062572-0
ISSN	1573-6660 ; 1040-7308
ISSN (online)	1573-6660
ISSN	1040-7308
DOI	10.1007/s11065-017-9364-2
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Article ; Online: Comprehensive characterization of elevated tau PET signal in the absence of amyloid-beta.

Weigand, Alexandra J / Edwards, Lauren E / Thomas, Kelsey R / Bangen, Katherine J / Bondi, Mark W

Brain communications

2022 Volume 4, Issue 6, Page(s) fcac272

Abstract: Recently proposed biomarker-only diagnostic frameworks propose that amyloid-beta is necessary for placement on the Alzheimer's disease continuum, whereas tau in the absence of amyloid-beta is considered to be a non-Alzheimer's disease pathologic change. ... ...

Abstract	Recently proposed biomarker-only diagnostic frameworks propose that amyloid-beta is necessary for placement on the Alzheimer's disease continuum, whereas tau in the absence of amyloid-beta is considered to be a non-Alzheimer's disease pathologic change. Similarly, the pathologic designation of tau in the absence of amyloid-beta is characterized as primary age-related tauopathy and separable from Alzheimer's disease. Our study sought to identify an early-to-moderate tau stage with minimal amyloid-beta using PET imaging and characterize these individuals in terms of clinical, cognitive and biological features. Seven hundred and three participants from the Alzheimer's Disease Neuroimaging Initiative were classified into one of the four groups (A-/T-, A-/T+, A+/T- and A+/T+) based on PET positivity or negativity for cortical amyloid-beta (A-/A+) and early-to-moderate stage (i.e. meta-temporal) tau (T-/T+). These groups were then compared on demographic and clinical features, vascular risk, multi-domain neuropsychological performance, multi-domain subjective cognitive complaints, apolipoprotein E epsilon-4 carrier status and cortical thickness across Alzheimer's disease-vulnerable regions. The proportion of participants classified in each group was as follows: 47.23% A-/T-, 13.51% A-/T+, 12.23% A+/T- and 27.03% A+/T+. Results indicated that the A-/T+ and A+/T+ groups did not statistically differ on age, sex, depression levels, vascular risk and cortical thickness across temporal and parietal regions. Additionally, both A-/T+ and A+/T+ groups showed significant associations between memory performance and cortical thickness of temporal regions. Despite the different pathologic terminology used for A-/T+ and A+/T+, these groups did not statistically differ on a number of clinical, cognitive and biomarker features. Although it remains unclear whether A-/T+ reflects a pathologic construct separable from Alzheimer's disease, our results provide evidence that this group typically characterized as 'non-Alzheimer's pathologic change' or 'primary age-related tauopathy' should be given increased attention, given some similarities in cognitive and biomarker characteristics to groups traditionally considered to be on the Alzheimer's continuum.
Language	English
Publishing date	2022-10-26
Publishing country	England
Document type	Journal Article
ISSN	2632-1297
ISSN (online)	2632-1297
DOI	10.1093/braincomms/fcac272
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Article: Characterizing cognitive profiles in diverse middle-aged and older Hispanics/Latinos: Study of Latinos-Investigation of Neurocognitive Aging (HCHS/SOL).

Graves, Lisa V / Tarraf, Wassim / Gonzalez, Kevin / Bondi, Mark W / Gallo, Linda C / Isasi, Carmen R / Daviglus, Martha / Lamar, Melissa / Zeng, Donglin / Cai, Jianwen / González, Hector M

Alzheimer's & dementia (Amsterdam, Netherlands)

2024 Volume 16, Issue 2, Page(s) e12592

Abstract: Introduction: We investigated cognitive profiles among diverse, middle-aged and older Hispanic/Latino adults in the Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA) cohort using a cross-sectional observational study design.: Methods: ...

Abstract	Introduction: We investigated cognitive profiles among diverse, middle-aged and older Hispanic/Latino adults in the Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA) cohort using a cross-sectional observational study design. Methods: Based on weighted descriptive statistics, the average baseline age of the target population was 56.4 years, slightly more than half were women (54.6%), and 38.4% reported less than a high school education. We used latent profile analysis of demographically adjusted Results: Statistical fit assessment indices combined with clinical interpretation suggested five profiles: (1) a Higher Global group performing in the average-to-high-average range across all cognitive and instrumental activity of daily living (IADL) tests (13.8%); (2) a Higher Memory group with relatively high performance on memory tests but average performance across all other cognitive/IADL tests (24.6%); (3) a Lower Memory group with relatively low performance on memory tests but average performance across all other cognitive/IADL tests (32.8%); (4) a Lower Executive Function group with relatively low performance on executive function and processing speed tests but average-to-low-average performance across all other cognitive/IADL tests (16.6%); and (5) a Lower Global group performing low-average-to-mildly impaired across all cognitive/IADL tests (12.1%). Discussion: Our results provide evidence of heterogeneity in the cognitive profiles of a representative, community-dwelling sample of diverse Hispanic/Latino adults. Our analyses yielded cognitive profiles that may assist efforts to better understand the early cognitive changes that may portend Alzheimer's disease and related dementias among diverse Hispanics/Latinos. Highlights: The present study characterized cognitive profiles among diverse middle-aged and older Hispanic/Latino adults.Latent profile analysis of neurocognitive test scores was the primary analysis conducted.The target population consists of middle-aged and older Hispanic/Latino adults enrolled in the Hispanic Community Health Study/Study of Latinos and ancillary Study of Latinos - Investigation of Neurocognitive Aging.
Language	English
Publishing date	2024-04-22
Publishing country	United States
Document type	Journal Article
ZDB-ID	2832898-X
ISSN	2352-8729
ISSN	2352-8729
DOI	10.1002/dad2.12592
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Article ; Online: APOE differentially moderates cerebrospinal fluid and plasma phosphorylated tau181 associations with multi-domain cognition.

Weigand, Alexandra J / Ortiz, Gema / Walker, Kayla S / Galasko, Douglas R / Bondi, Mark W / Thomas, Kelsey R

Neurobiology of aging

2023 Volume 125, Page(s) 1–8

Abstract: Biofluid markers of phosphorylated tau181 (p-tau181) are increasingly popular for the detection of early Alzheimer's pathologic changes. However, the differential dynamics of cerebrospinal fluid (CSF) and plasma p-tau181 remain under investigation. We ... ...

Abstract	Biofluid markers of phosphorylated tau181 (p-tau181) are increasingly popular for the detection of early Alzheimer's pathologic changes. However, the differential dynamics of cerebrospinal fluid (CSF) and plasma p-tau181 remain under investigation. We studied 727 participants from the Alzheimer's Disease Neuroimaging Initiative with plasma and CSF p-tau181 data, apolipoprotein (APOE) ε4 carrier status, amyloid positron emission tomography (PET) imaging, and neuropsychological data. Higher levels of plasma and CSF p-tau181 were observed among APOE ε4 carriers. CSF and plasma p-tau181 were significantly associated with memory, and this effect was greater in APOE ε4 carriers. However, whereas CSF p-tau181 was not significantly associated with language or attention/executive function among ε4 carriers or non-carriers, APOE ε4 status moderated the association of plasma p-tau181 with both language and attention/executive function. These findings lend support to the notion that p-tau181 biofluid markers are useful in measuring AD pathologic changes but also suggest that CSF and plasma p-tau181 have unique properties and dynamics that should be considered when using these markers in research and clinical practice.
MeSH term(s)	Humans ; Alzheimer Disease/diagnosis ; Amyloid beta-Peptides/cerebrospinal fluid ; Apolipoprotein E4/genetics ; Apolipoprotein E4/cerebrospinal fluid ; Biomarkers/cerebrospinal fluid ; Cognition ; tau Proteins/cerebrospinal fluid
Chemical Substances	Amyloid beta-Peptides ; Apolipoprotein E4 ; Biomarkers ; tau Proteins ; ApoE protein, human
Language	English
Publishing date	2023-01-18
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	604505-4
ISSN	1558-1497 ; 0197-4580
ISSN (online)	1558-1497
ISSN	0197-4580
DOI	10.1016/j.neurobiolaging.2022.10.016
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Article ; Online: Cognitive reserve moderates the association between cerebral blood flow and language performance in older adults with mild cognitive impairment.

Brenner, Einat K / Thomas, Kelsey R / Weigand, Alexandra J / Edwards, Lauren / Edmonds, Emily C / Bondi, Mark W / Bangen, Katherine J

Neurobiology of aging

2023 Volume 125, Page(s) 83–89

Abstract: Higher cognitive reserve (CR) may offer protection from cognitive changes associated with reduced cerebral blood flow (CBF). We investigated CR as a moderator of the effect of CBF on cognition in older adults with mild cognitive impairment (MCI; N = 46) ... ...

Abstract	Higher cognitive reserve (CR) may offer protection from cognitive changes associated with reduced cerebral blood flow (CBF). We investigated CR as a moderator of the effect of CBF on cognition in older adults with mild cognitive impairment (MCI; N = 46) and those who are cognitively unimpaired (CU; N = 101). Participants underwent arterial spin labeling MRI, which was used to quantify CBF in 4 a priori regions. Estimated verbal intelligence quotient (VIQ) served as a proxy for CR. Multiple linear regressions examined whether VIQ moderated associations between CBF and cognition and whether this differed by cognitive status. Outcomes included memory and language performance. There were 3-way interactions (CBFVIQcognitive status) on category fluency when examining hippocampal, superior frontal, and inferior frontal CBF. Follow-up analyses revealed that, within the MCI but not CU group, there were CBF*VIQ interactions on fluency in all a priori regions examined, where there were stronger, positive associations between CBF and fluency at higher VIQ. Conclusion: In MCI, higher CR plays a role in strengthening CBF-fluency associations.
MeSH term(s)	Humans ; Aged ; Cognitive Reserve ; Cognitive Dysfunction/psychology ; Cognition/physiology ; Language ; Magnetic Resonance Imaging ; Cerebrovascular Circulation/physiology
Language	English
Publishing date	2023-02-02
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, Non-U.S. Gov't
ZDB-ID	604505-4
ISSN	1558-1497 ; 0197-4580
ISSN (online)	1558-1497
ISSN	0197-4580
DOI	10.1016/j.neurobiolaging.2023.01.012
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Article ; Online: Brain Derived Neurotrophic Factor Interacts with White Matter Hyperintensities to Influence Processing Speed and Hippocampal Volume in Older Adults.

Brenner, Einat K / Weigand, Alexandra J / Edwards, Lauren / Thomas, Kelsey R / Edmonds, Emily C / Bondi, Mark W / Bangen, Katherine J

Journal of Alzheimer's disease : JAD

2023 Volume 93, Issue 1, Page(s) 141–149

Abstract: Background: Brain-derived neurotrophic factor (BDNF) is a neurotrophin that plays an important role in regulating synaptic activity and plasticity.: Objective: Given that type-2 diabetes (T2DM) increases the risk of cognitive decline, and studies ... ...

Abstract	Background: Brain-derived neurotrophic factor (BDNF) is a neurotrophin that plays an important role in regulating synaptic activity and plasticity. Objective: Given that type-2 diabetes (T2DM) increases the risk of cognitive decline, and studies have suggested lower BDNF levels may be a risk factor of diabetic neurovascular complications, we sought to investigate total white matter hyperintensities (WMH) as a moderator of the effect of BDNF on hippocampal volume and cognition. Methods: Older adults without dementia from the Alzheimer's Disease Neuroimaging Initiative (N = 454 including 49 with T2DM and 405 without diabetes) underwent neuropsychological evaluation, magnetic resonance imaging to quantify hippocampal and WMH volumes, and blood draw to assess BDNF. Results: Adjusting for age, sex, and APOE ɛ4 carrier status, there was a significant interaction between total WMH and BDNF on bilateral hippocampal volume in the non-T2DM group (t = 2.63, p = 0.009). Examination of main effect models with a dichotomous high/low BNDF group revealed a significant main effect for low BDNF (t = -4.98, p < 0.001), such that as WMH increased, bilateral hippocampal volume decreased. There was also a significant interaction between total WMH and BDNF on processing speed in the non-T2DM group (t = 2.91, p = 0.004). There was a significant main effect for low BDNF (t = -3.55, p < 0.001) such that as WMH increased, processing speed decreased. The interactions were not significant in the T2DM group. Conclusion: These results further elucidate the protective role that BDNF plays on cognition, as well as the cognitive effects of WMH.
MeSH term(s)	Humans ; Aged ; Brain-Derived Neurotrophic Factor ; White Matter/diagnostic imaging ; White Matter/pathology ; Processing Speed ; Cognition/physiology ; Cognitive Dysfunction/psychology ; Magnetic Resonance Imaging ; Hippocampus/diagnostic imaging ; Hippocampus/pathology ; Brain/pathology
Chemical Substances	Brain-Derived Neurotrophic Factor
Language	English
Publishing date	2023-03-27
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	1440127-7
ISSN	1875-8908 ; 1387-2877
ISSN (online)	1875-8908
ISSN	1387-2877
DOI	10.3233/JAD-221178
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