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Article ; Online: Risk of Neuropsychiatric Symptoms Among People Who Develop Cognitive Impairment With and Without a History of Post-traumatic Stress Disorder.

Perales-Puchalt, Jaime / Gauthreaux, Kathryn / Flatt, Jason D / Meyer, Oanh L / Kukull, Walter A

Alzheimer disease and associated disorders

2023 Volume 38, Issue 1, Page(s) 91–94

Abstract: We aimed to prospectively assess the change in neuropsychiatric symptoms among people who develop cognitive impairment and have a history of post-traumatic stress disorder (PTSD). We analyzed longitudinal data from the National Alzheimer's Coordinating ... ...

Abstract	We aimed to prospectively assess the change in neuropsychiatric symptoms among people who develop cognitive impairment and have a history of post-traumatic stress disorder (PTSD). We analyzed longitudinal data from the National Alzheimer's Coordinating Center Unified Data Set (March 2015 to December 2021). Analyses included individuals who were cognitively normal and who had nonmissing assessment of PTSD at the initial visit and had at least 1 follow-up visit with cognitive impairment. We compared the difference in the mean neuropsychiatric symptom score at the first Unified Data Set visit versus the first visit with a Clinical Dementia Rating of 0.5 between those with and without a history of PTSD. The mean neuropsychiatric symptom score change did not differ between those with and without a history of PTSD (1.06 vs. 0.77, respectively; P =0.79). The null results found in this study warrant future research. Several methodological limitations might explain these results.
MeSH term(s)	Humans ; Stress Disorders, Post-Traumatic/diagnosis ; Cognitive Dysfunction/psychology
Language	English
Publishing date	2023-12-28
Publishing country	United States
Document type	Journal Article
ZDB-ID	1002700-2
ISSN	1546-4156 ; 0893-0341
ISSN (online)	1546-4156
ISSN	0893-0341
DOI	10.1097/WAD.0000000000000594
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Article ; Online: Cognitive Aging with Dementia, Mild Cognitive Impairment, or No Impairment: A Comparison of Same- and Mixed-Sex Couples.

Correro Ii, Anthony N / Gauthreaux, Kathryn / Perales-Puchalt, Jaime / Chen, Yen-Chi / Chan, Kwun C G / Kukull, Walter A / Flatt, Jason D

Journal of Alzheimer's disease : JAD

2023 Volume 92, Issue 1, Page(s) 109–128

Abstract: Background: Lesbian and gay older adults have health disparities that are risk factors for Alzheimer's disease, yet little is known about the neurocognitive aging of sexual minority groups.: Objective: To explore cross-sectional and longitudinal ... ...

Abstract	Background: Lesbian and gay older adults have health disparities that are risk factors for Alzheimer's disease, yet little is known about the neurocognitive aging of sexual minority groups. Objective: To explore cross-sectional and longitudinal dementia outcomes for adults in same-sex relationships (SSR) and those in mixed-sex relationships (MSR). Methods: This prospective observational study utilized data from the National Alzheimer's Coordinating Center Uniform Data Set (NACC UDS) collected from contributing Alzheimer's Disease Research Centers. Participants were adults aged 55+ years at baseline with at least two visits in NACC UDS (from September 2005 to March 2021) who had a spouse, partner, or companion as a co-participant. Outcome measures included CDR® Dementia Staging Instrument, NACC UDS neuropsychological testing, and the Functional Activities Questionnaire. Multivariable linear mixed-effects models accounted for center clustering and repeated measures by individual. Results: Both MSR and SSR groups experienced cognitive decline regardless of baseline diagnosis. In general, MSR and SSR groups did not differ statistically on cross-sectional or longitudinal estimates of functioning, dementia severity, or neuropsychological testing, with two primary exceptions. People in SSR with mild cognitive impairment showed less functional impairment at baseline (FAQ M = 2.61, SD = 3.18 vs. M = 3.97, SD = 4.53, respectively; p < 0.01). The SSR group with dementia had less steep decline in attention/working memory (β estimates = -0.10 versus -0.18; p < 0.01). Conclusion: Participants in SSR did not show cognitive health disparities consistent with a minority stress model. Additional research into protective factors is warranted.
MeSH term(s)	Female ; Humans ; Aged ; Alzheimer Disease/psychology ; Cognitive Aging ; Cross-Sectional Studies ; Cognitive Dysfunction/psychology ; Neuropsychological Tests
Language	English
Publishing date	2023-01-14
Publishing country	Netherlands
Document type	Observational Study ; Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1440127-7
ISSN	1875-8908 ; 1387-2877
ISSN (online)	1875-8908
ISSN	1387-2877
DOI	10.3233/JAD-220309
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Article ; Online: An apple a day to prevent Parkinson disease: reduction of risk by flavonoids.

Kukull, Walter A

Neurology

2012 Volume 78, Issue 15, Page(s) 1112–1113

MeSH term(s)	Feeding Behavior ; Female ; Flavonoids/administration & dosage ; Humans ; Male ; Parkinson Disease/epidemiology ; Parkinson Disease/prevention & control
Chemical Substances	Flavonoids
Language	English
Publishing date	2012-04-04
Publishing country	United States
Document type	Editorial ; Research Support, N.I.H., Extramural ; Comment
ZDB-ID	207147-2
ISSN	1526-632X ; 0028-3878
ISSN (online)	1526-632X
ISSN	0028-3878
DOI	10.1212/WNL.0b013e31824f80e4
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Article ; Online: Psychosis in Alzheimer's disease is associated with specific changes in brain MRI volume, cognition and neuropathology.

Almeida, Francisco C / Jesus, Tiago / Coelho, Ana / Quintas-Neves, Miguel / Gauthreaux, Kathryn / Teylan, Merilee A / Mock, Charles N / Kukull, Walter A / Crary, John F / Oliveira, Tiago Gil

Neurobiology of aging

2024 Volume 138, Page(s) 10–18

Abstract: Psychosis in Alzheimer's Disease (AD) is prevalent and indicates poor prognosis. However, the neuropathological, cognitive and brain atrophy patterns underlying these symptoms have not been fully elucidated. In this study, we evaluated 178 patients with ... ...

Abstract	Psychosis in Alzheimer's Disease (AD) is prevalent and indicates poor prognosis. However, the neuropathological, cognitive and brain atrophy patterns underlying these symptoms have not been fully elucidated. In this study, we evaluated 178 patients with AD neuropathological change (ADNC) and ante-mortem volumetric brain magnetic resonance imaging (MRI). Presence of psychosis was determined using the Neuropsychiatric Inventory Questionnaire. Clinical Dementia Rating Sum-of-boxes (CDR-SB) was longitudinally compared between groups with a follow-up of 3000 days using mixed-effects multiple linear regression. Neuropsychological tests closest to the time of MRI and brain regional volumes were cross-sectionally compared. Psychosis was associated with lower age of death, higher longitudinal CDR-SB scores, multi-domain cognitive deficits, higher neuritic plaque severity, Braak stage, Lewy Body pathology (LB) and right temporal lobe regional atrophy. Division according to the presence of LB showed differential patterns of AD-typical pathology, cognitive deficits and regional atrophy. In conclusion, psychosis in ADNC with and without LB has clinical value and associates with subgroup patterns of neuropathology, cognition and regional atrophy.
MeSH term(s)	Humans ; Alzheimer Disease/diagnosis ; Cognition ; Brain/diagnostic imaging ; Brain/pathology ; Magnetic Resonance Imaging/methods ; Psychotic Disorders/diagnostic imaging ; Atrophy/pathology
Language	English
Publishing date	2024-03-02
Publishing country	United States
Document type	Journal Article
ZDB-ID	604505-4
ISSN	1558-1497 ; 0197-4580
ISSN (online)	1558-1497
ISSN	0197-4580
DOI	10.1016/j.neurobiolaging.2024.02.013
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Article ; Online: Commentary on "a roadmap for the prevention of dementia II: Leon Thal Symposium 2008." "Big Asks": what can be changed to increase and speed progress on Alzheimer's disease research and treatment?

Kukull, Walter A

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

2009 Volume 5, Issue 2, Page(s) 137–139

MeSH term(s)	Academic Medical Centers/organization & administration ; Academic Medical Centers/standards ; Academic Medical Centers/trends ; Access to Information/legislation & jurisprudence ; Aged ; Alzheimer Disease/diagnosis ; Alzheimer Disease/etiology ; Alzheimer Disease/therapy ; Biomedical Research/organization & administration ; Biomedical Research/standards ; Biomedical Research/trends ; Cohort Studies ; Diagnosis, Differential ; Humans ; Medical Records/legislation & jurisprudence ; Medical Records/standards ; Multicenter Studies as Topic/standards ; Multicenter Studies as Topic/trends ; National Institute on Aging (U.S.)/organization & administration ; National Institute on Aging (U.S.)/standards ; Research Support as Topic/standards ; Research Support as Topic/trends ; United States
Language	English
Publishing date	2009-03-26
Publishing country	United States
Document type	Comment ; Editorial
ZDB-ID	2211627-8
ISSN	1552-5279 ; 1552-5260
ISSN (online)	1552-5279
ISSN	1552-5260
DOI	10.1016/j.jalz.2009.01.003
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Article ; Online: Genetic associations with dementia-related proteinopathy: Application of item response theory.

Katsumata, Yuriko / Fardo, David W / Shade, Lincoln M P / Wu, Xian / Karanth, Shama D / Hohman, Timothy J / Schneider, Julie A / Bennett, David A / Farfel, Jose M / Gauthreaux, Kathryn / Mock, Charles / Kukull, Walter A / Abner, Erin L / Nelson, Peter T

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

2024 Volume 20, Issue 4, Page(s) 2906–2921

Abstract: Introduction: Although dementia-related proteinopathy has a strong negative impact on public health, and is highly heritable, understanding of the related genetic architecture is incomplete.: Methods: We applied multidimensional generalized partial ... ...

Abstract	Introduction: Although dementia-related proteinopathy has a strong negative impact on public health, and is highly heritable, understanding of the related genetic architecture is incomplete. Methods: We applied multidimensional generalized partial credit modeling (GPCM) to test genetic associations with dementia-related proteinopathies. Data were analyzed to identify candidate single nucleotide variants for the following proteinopathies: Aβ, tau, α-synuclein, and TDP-43. Results: Final included data comprised 966 participants with neuropathologic and WGS data. Three continuous latent outcomes were constructed, corresponding to TDP-43-, Aβ/Tau-, and α-synuclein-related neuropathology endophenotype scores. This approach helped validate known genotype/phenotype associations: for example, TMEM106B and GRN were risk alleles for TDP-43 pathology; and GBA for α-synuclein/Lewy bodies. Novel suggestive proteinopathy-linked alleles were also discovered, including several (SDHAF1, TMEM68, and ARHGEF28) with colocalization analyses and/or high degrees of biologic credibility. Discussion: A novel methodology using GPCM enabled insights into gene candidates for driving misfolded proteinopathies. Highlights: Latent factor scores for proteinopathies were estimated using a generalized partial credit model. The three latent continuous scores corresponded well with proteinopathy severity. Novel genes associated with proteinopathies were identified. Several genes had high degrees of biologic credibility for dementia risk factors.
MeSH term(s)	Humans ; alpha-Synuclein/genetics ; TDP-43 Proteinopathies/genetics ; TDP-43 Proteinopathies/pathology ; Proteostasis Deficiencies ; Dementia/genetics ; DNA-Binding Proteins ; Biological Products ; Alzheimer Disease/pathology ; Membrane Proteins/genetics ; Nerve Tissue Proteins/genetics
Chemical Substances	alpha-Synuclein ; DNA-Binding Proteins ; Biological Products ; TMEM106B protein, human ; Membrane Proteins ; Nerve Tissue Proteins
Language	English
Publishing date	2024-03-09
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.13741
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Article ; Online: Demographically-adjusted normative data among Latinos for the version 3 of the Alzheimer's Disease Centers' Neuropsychological Test Battery in the Uniform Data Set.

Marquine, María J / Parks, Adam / Perales-Puchalt, Jaime / González, David A / Rosado-Bruno, Mónica / North, Rebecca / Pieper, Carl / Werry, Amy E / Kiselica, Andrew / Chapman, Silvia / Dodge, Hiroko / Gauthreaux, Kathryn / Kukull, Walter A / Rascovsky, Katya

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

2023 Volume 19, Issue 9, Page(s) 4174–4186

Abstract: Introduction: We developed demographically-adjusted normative data for Spanish- and English-speaking Latinos on the Version 3.0 of the National Alzheimer's Coordinating Center Uniform Data Set Neuropsychological Battery (UDS3-NB).: Methods: Healthy ... ...

Abstract	Introduction: We developed demographically-adjusted normative data for Spanish- and English-speaking Latinos on the Version 3.0 of the National Alzheimer's Coordinating Center Uniform Data Set Neuropsychological Battery (UDS3-NB). Methods: Healthy Latino adults (N = 437) age 50-94 (191 Spanish- and 246 English-speaking) enrolled in Alzheimer's Disease Research Centers completed the UDS3-NB in their preferred language. Normative data were developed via multiple linear regression models on UDS3-NB raw scores stratified by language group with terms for demographic characteristics (age, years of formal education, and sex). Results: Younger age and more years of education were associated with better performance on most tests in both language groups, with education being particularly influential on raw scores among Spanish-speakers. Sex effects varied across tests and language groups. Discussion: These normative data are a crucial step toward improving diagnostic accuracy of the UDS3-NB for neurocognitive disorders among Latinos in the United States and addressing disparities in Alzheimer's disease and related dementias. Highlights: We developed normative data on the UDS3-NB for Latinos in the US ages 50-94. Younger age and more years of education were linked to better raw scores in several cognitive tests. Education was particularly influential on raw scores among Spanish-speakers. Sex effects varied across tests and between English- and Spanish-speaking Latinos. These normative data might improve diagnostic accuracy of the UDS3-NB among Latinos.
MeSH term(s)	Humans ; United States ; Middle Aged ; Aged ; Aged, 80 and over ; Alzheimer Disease/diagnosis ; Language ; Neuropsychological Tests ; Educational Status ; Hispanic or Latino
Language	English
Publishing date	2023-06-25
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2211627-8
ISSN	1552-5279 ; 1552-5260
ISSN (online)	1552-5279
ISSN	1552-5260
DOI	10.1002/alz.13313
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Article ; Online: Prescribing anti-amyloid immunotherapies to treat Alzheimer's disease: Fully informing patient decisions.

Greenberg, Barry D / Lemere, Cynthia A / Barnes, Lisa L / Hayden, Kathleen M / Kukull, Walter A / Oh, Esther S / Snyder, Peter J / Supiano, Mark / Dilworth-Anderson, Peggye

Alzheimer's & dementia (New York, N. Y.)

2023 Volume 9, Issue 4, Page(s) e12426

Language	English
Publishing date	2023-10-04
Publishing country	United States
Document type	Editorial
ZDB-ID	2832891-7
ISSN	2352-8737 ; 2352-8737
ISSN (online)	2352-8737
ISSN	2352-8737
DOI	10.1002/trc2.12426
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Article ; Online: Identifying individuals with non-Alzheimer's disease co-pathologies: A precision medicine approach to clinical trials in sporadic Alzheimer's disease.

Tosun, Duygu / Yardibi, Ozlem / Benzinger, Tammie L S / Kukull, Walter A / Masters, Colin L / Perrin, Richard J / Weiner, Michael W / Simen, Arthur / Schwarz, Adam J

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

2023 Volume 20, Issue 1, Page(s) 421–436

Abstract: Introduction: Biomarkers remain mostly unavailable for non-Alzheimer's disease neuropathological changes (non-ADNC) such as transactive response DNA-binding protein 43 (TDP-43) proteinopathy, Lewy body disease (LBD), and cerebral amyloid angiopathy (CAA) ...

Abstract	Introduction: Biomarkers remain mostly unavailable for non-Alzheimer's disease neuropathological changes (non-ADNC) such as transactive response DNA-binding protein 43 (TDP-43) proteinopathy, Lewy body disease (LBD), and cerebral amyloid angiopathy (CAA). Methods: A multilabel non-ADNC classifier using magnetic resonance imaging (MRI) signatures was developed for TDP-43, LBD, and CAA in an autopsy-confirmed cohort (N = 214). Results: A model using demographic, genetic, clinical, MRI, and ADNC variables (amyloid positive [Aβ+] and tau+) in autopsy-confirmed participants showed accuracies of 84% for TDP-43, 81% for LBD, and 81% to 93% for CAA, outperforming reference models without MRI and ADNC biomarkers. In an ADNI cohort (296 cognitively unimpaired, 401 mild cognitive impairment, 188 dementia), Aβ and tau explained 33% to 43% of variance in cognitive decline; imputed non-ADNC explained an additional 16% to 26%. Accounting for non-ADNC decreased the required sample size to detect a 30% effect on cognitive decline by up to 28%. Discussion: Our results lead to a better understanding of the factors that influence cognitive decline and may lead to improvements in AD clinical trial design.
MeSH term(s)	Humans ; Alzheimer Disease/pathology ; Precision Medicine ; Cerebral Amyloid Angiopathy ; Lewy Body Disease/pathology ; DNA-Binding Proteins/metabolism ; Biomarkers
Chemical Substances	DNA-Binding Proteins ; Biomarkers
Language	English
Publishing date	2023-09-04
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.13447
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Article ; Online: Different cohort, disparate results: Selection bias is a key factor in autopsy cohorts.

Gauthreaux, Kathryn / Kukull, Walter A / Nelson, Karin B / Mock, Charles / Chen, Yen-Chi / Chan, Kwun C G / Fardo, David W / Katsumata, Yuriko / Abner, Erin L / Nelson, Peter T

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

2023 Volume 20, Issue 1, Page(s) 266–277

Abstract: Introduction: Research-oriented autopsy cohorts provide critical insights into dementia pathobiology. However, different studies sometimes report disparate findings, partially because each study has its own recruitment biases. We hypothesized that a ... ...

Abstract	Introduction: Research-oriented autopsy cohorts provide critical insights into dementia pathobiology. However, different studies sometimes report disparate findings, partially because each study has its own recruitment biases. We hypothesized that a straightforward metric, related to the percentage of research volunteers cognitively normal at recruitment, would predict other inter-cohort differences. Methods: The National Alzheimer's Coordinating Center (NACC) provided data on N = 7178 autopsied participants from 28 individual research centers. Research cohorts were grouped based on the proportion of participants with normal cognition at initial clinical visit. Results: Cohorts with more participants who were cognitively normal at recruitment contained more individuals who were older, female, had lower frequencies of apolipoprotein E ε4, Lewy body disease, and frontotemporal dementia, but higher rates of cerebrovascular disease. Alzheimer's disease (AD) pathology was little different between groups. Discussion: The percentage of participants recruited while cognitively normal predicted differences in findings in autopsy research cohorts. Most differences were in non-AD pathologies. Highlights: Systematic differences exist between autopsy cohorts that serve dementia research. We propose a metric to use for gauging a research-oriented autopsy cohort. It is essential to consider the characteristics of autopsy cohorts.
MeSH term(s)	Humans ; Female ; Selection Bias ; Alzheimer Disease/pathology ; Lewy Body Disease/pathology ; Cerebrovascular Disorders ; Autopsy
Language	English
Publishing date	2023-08-17
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.13422
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