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Article ; Online: Donanemab for Alzheimer Disease-Who Benefits and Who Is Harmed?

Manly, Jennifer J / Deters, Kacie D

2023 Volume 330, Issue 6, Page(s) 510–511

MeSH term(s)	Humans ; Alzheimer Disease/drug therapy ; Self-Injurious Behavior ; Risk Factors ; Antibodies, Monoclonal
Chemical Substances	Antibodies, Monoclonal
Language	English
Publishing date	2023-07-17
Publishing country	United States
Document type	Editorial ; Comment
ZDB-ID	2958-0
ISSN	1538-3598 ; 0254-9077 ; 0002-9955 ; 0098-7484
ISSN (online)	1538-3598
ISSN	0254-9077 ; 0002-9955 ; 0098-7484
DOI	10.1001/jama.2023.11704
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Article ; Online: What the Aducanumab Approval Reveals About Alzheimer Disease Research.

Manly, Jennifer J / Glymour, M Maria

JAMA neurology

2021 Volume 78, Issue 11, Page(s) 1305–1306

MeSH term(s)	Alzheimer Disease/drug therapy ; Antibodies, Monoclonal, Humanized/therapeutic use ; Clinical Trials as Topic/methods ; Clinical Trials as Topic/standards ; Drug Approval ; Ethnic and Racial Minorities ; Humans ; United States ; United States Food and Drug Administration
Chemical Substances	Antibodies, Monoclonal, Humanized ; aducanumab (105J35OE21)
Language	English
Publishing date	2021-09-22
Publishing country	United States
Document type	Journal Article
ZDB-ID	2702023-X
ISSN	2168-6157 ; 2168-6149
ISSN (online)	2168-6157
ISSN	2168-6149
DOI	10.1001/jamaneurol.2021.3404
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Article ; Online: Childhood Maltreatment and Dementia Risk Factors in Midlife: A Prospective Investigation.

Widom, Cathy S / Do, Hang H / Lynch, Kristin S / Manly, Jennifer J

Current Alzheimer research

2023 Volume 20, Issue 9, Page(s) 636–647

Abstract: Background: Previous studies have linked childhood adversities to dementia risk, yet most studies are cross-sectional in design and utilize retrospective self-reports to assess childhood experiences. These design characteristics make it difficult to ... ...

Abstract	Background: Previous studies have linked childhood adversities to dementia risk, yet most studies are cross-sectional in design and utilize retrospective self-reports to assess childhood experiences. These design characteristics make it difficult to establish temporal order and draw firm conclusions. Objectives: Using a longitudinal design, we sought to determine whether childhood maltreatment predicts dementia risk factors in middle adulthood. Methods: Data have been obtained from a prospective cohort design study of children with documented cases of childhood maltreatment (ages 0-11 years at case identification) and demographically matched controls who were followed up and interviewed in middle adulthood. Outcomes were assessed through a medical examination and interview, and 807 of the cases that included blood collection at mean age 41. Dementia risk were investigated using 11 potentially modifiable risk factors. Results: Compared to controls, individuals with histories of childhood maltreatment had a higher risk of low educational attainment, low social contact, smoking, and clinical depression, and a higher total number of dementia risk factors. In general, childhood maltreatment predicted a higher risk of dementia for females, males, and Black and White participants. Black maltreated participants had a greater risk for traumatic brain injury compared to Black controls. Physical abuse, sexual abuse, and neglect, each predicted a higher number of dementia risk factors in mid-life. Conclusion: These findings provide evidence that childhood maltreatment increases the risk for dementia in mid-life and has a demonstrable impact lasting over 30 years. Reducing the prevalence of mid-life dementia risk factors could reduce the risk of later-life dementia.
MeSH term(s)	Child ; Male ; Female ; Humans ; Adult ; Child Abuse ; Retrospective Studies ; Prospective Studies ; Cross-Sectional Studies ; Risk Factors ; Dementia/epidemiology ; Dementia/etiology
Language	English
Publishing date	2023-12-28
Publishing country	United Arab Emirates
Document type	Journal Article
ZDB-ID	2205170-3
ISSN	1875-5828 ; 1567-2050
ISSN (online)	1875-5828
ISSN	1567-2050
DOI	10.2174/0115672050281539231222071355
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Article ; Online: Association of Stress With Cognitive Function Among Older Black and White US Adults.

Kulshreshtha, Ambar / Alonso, Alvaro / McClure, Leslie A / Hajjar, Ihab / Manly, Jennifer J / Judd, Suzanne

JAMA network open

2023 Volume 6, Issue 3, Page(s) e231860

Abstract: Importance: Perceived stress can have long-term physiological and psychological consequences and has shown to be a modifiable risk factor for Alzheimer disease and related dementias.: Objective: To investigate the association between perceived stress ...

Abstract	Importance: Perceived stress can have long-term physiological and psychological consequences and has shown to be a modifiable risk factor for Alzheimer disease and related dementias. Objective: To investigate the association between perceived stress and cognitive impairment in a large cohort study of Black and White participants aged 45 years or older. Design, setting, and participants: The Reasons for Geographic and Racial Differences in Stroke (REGARDS) study is a national population-based cohort of 30 239 Black and White participants aged 45 years or older, sampled from the US population. Participants were recruited from 2003 to 2007, with ongoing annual follow-up. Data were collected by telephone, self-administered questionnaires, and an in-home examination. Statistical analysis was performed from May 2021 to March 2022. Exposures: Perceived stress was measured using the 4-item version of the Cohen Perceived Stress Scale. It was assessed at the baseline visit and during 1 follow-up visit. Main outcomes and measures: Cognitive function was assessed with the Six-Item Screener (SIS); participants with a score below 5 were considered to have cognitive impairment. Incident cognitive impairment was defined as a shift from intact cognition (SIS score >4) at the first assessment to impaired cognition (SIS score ≤4) at the latest available assessment. Results: The final analytical sample included 24 448 participants (14 646 women [59.9%]; median age, 64 years [range, 45-98 years]; 10 177 Black participants [41.6%] and 14 271 White participants [58.4%]). A total of 5589 participants (22.9%) reported elevated levels of stress. Elevated levels of perceived stress (dichotomized as low stress vs elevated stress) were associated with 1.37 times higher odds of poor cognition after adjustment for sociodemographic variables, cardiovascular risk factors, and depression (adjusted odds ratio [AOR], 1.37; 95% CI, 1.22-1.53). The association of the change in the Perceived Stress Scale score with incident cognitive impairment was significant in both the unadjusted model (OR, 1.62; 95% CI, 1.46-1.80) and after adjustment for sociodemographic variables, cardiovascular risk factors, and depression (AOR, 1.39; 95% CI, 1.22-1.58). There was no interaction with age, race, and sex. Conclusions and relevance: This study suggests that there is an independent association between perceived stress and both prevalent and incident cognitive impairment. The findings suggest the need for regular screening and targeted interventions for stress among older adults.
MeSH term(s)	Aged ; Female ; Humans ; Middle Aged ; Cognition ; Cognitive Dysfunction/epidemiology ; Cohort Studies ; White ; Black or African American ; United States ; Aged, 80 and over ; Male ; Stress, Psychological/epidemiology
Language	English
Publishing date	2023-03-01
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ISSN	2574-3805
ISSN (online)	2574-3805
DOI	10.1001/jamanetworkopen.2023.1860
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Article ; Online: Inclusion of Underrepresented Groups in Preclinical Alzheimer Disease Trials-Opportunities Abound.

Manly, Jennifer J / Gilmore-Bykovskyi, Andrea / Deters, Kacie D

JAMA network open

2021 Volume 4, Issue 7, Page(s) e2114606

MeSH term(s)	Alzheimer Disease ; Humans ; Minority Groups ; Patient Selection
Language	English
Publishing date	2021-07-01
Publishing country	United States
Document type	Journal Article ; Comment
ISSN	2574-3805
ISSN (online)	2574-3805
DOI	10.1001/jamanetworkopen.2021.14606
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Article ; Online: Compulsory Schooling Laws as quasi-experiments for the health effects of education: Reconsidering mechanisms to understand inconsistent results.

Glymour, M Maria / Manly, Jennifer J

Social science & medicine (1982)

2018 Volume 214, Page(s) 67–69

MeSH term(s)	Educational Status ; Health Status ; Humans ; Research Design ; Schools/legislation & jurisprudence ; Social Determinants of Health ; United States
Language	English
Publishing date	2018-08-16
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	4766-1
ISSN	1873-5347 ; 0037-7856 ; 0277-9536
ISSN (online)	1873-5347
ISSN	0037-7856 ; 0277-9536
DOI	10.1016/j.socscimed.2018.08.008
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Article ; Online: Factor structure of the Harmonized Cognitive Assessment Protocol neuropsychological battery in the Health and Retirement Study.

Jones, Richard N / Manly, Jennifer J / Langa, Kenneth M / Ryan, Lindsay H / Levine, Deborah A / McCammon, Ryan / Weir, David

Journal of the International Neuropsychological Society : JINS

2023 Volume 30, Issue 1, Page(s) 47–55

Abstract: Objective: The Harmonized Cognitive Assessment Protocol (HCAP) describes an assessment battery and a family of population-representative studies measuring neuropsychological performance. We describe the factorial structure of the HCAP battery in the US ... ...

Abstract	Objective: The Harmonized Cognitive Assessment Protocol (HCAP) describes an assessment battery and a family of population-representative studies measuring neuropsychological performance. We describe the factorial structure of the HCAP battery in the US Health and Retirement Study (HRS). Method: The HCAP battery was compiled from existing measures by a cross-disciplinary and international panel of researchers. The HCAP battery was used in the 2016 wave of the HRS. We used factor analysis methods to assess and refine a theoretically driven single and multiple domain factor structure for tests included in the HCAP battery among 3,347 participants with evaluable performance data. Results: For the eight domains of cognitive functioning identified (orientation, memory [immediate, delayed, and recognition], set shifting, attention/speed, language/fluency, and visuospatial), all single factor models fit reasonably well, although four of these domains had either 2 or 3 indicators where fit must be perfect and is not informative. Multidimensional models suggested the eight-domain model was overly complex. A five-domain model (orientation, memory delayed and recognition, executive functioning, language/fluency, visuospatial) was identified as a reasonable model for summarizing performance in this sample (standardized root mean square residual = 0.05, root mean square error of approximation = 0.05, confirmatory fit index = 0.94). Conclusions: The HCAP battery conforms adequately to a multidimensional structure of neuropsychological performance. The derived measurement models can be used to operationalize notions of neurocognitive impairment, and as a starting point for prioritizing pre-statistical harmonization and evaluating configural invariance in cross-national research.
MeSH term(s)	Humans ; Retirement ; Neuropsychological Tests ; Cognition ; Executive Function ; Attention ; Cognitive Dysfunction/diagnosis
Language	English
Publishing date	2023-07-14
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/S135561772300019X
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Article ; Online: Recommendations on Social Determinants of Health in Neurologic Disease.

Towfighi, Amytis / Berger, Rachel P / Corley, Alexandra M S / Glymour, M Maria / Manly, Jennifer J / Skolarus, Lesli E

Neurology

2023 Volume 101, Issue 7 Suppl 1, Page(s) S17–S26

Abstract: Social determinants of health (SDOH) are increasingly recognized as important drivers of inequities in neurologic disease and outcomes. However, our understanding of the biopsychosocial mechanisms by which SDOH affect neurologic disease remains in its ... ...

Abstract	Social determinants of health (SDOH) are increasingly recognized as important drivers of inequities in neurologic disease and outcomes. However, our understanding of the biopsychosocial mechanisms by which SDOH affect neurologic disease remains in its infancy. The most robust epidemiologic research has been on the associations between education, schooling, and place-based social determinants on cognition, dementia, and cerebrovascular disease later in life. Further research is needed to more deeply understand the complex interplay of SDOH on neurologic disease. Few SDOH screening tools have been validated in populations with neurologic disease. In addition, comparison across studies and populations is hampered by lack of standardized common data elements. Experiences of populations historically underrepresented in research should be centered in future research studies, and changes should be made in recruitment expectations and measurement choices. For research on inequities, it is critical to support and incentivize institutional infrastructure to foster meaningful engagement with populations affected by research. Finally, it remains to be seen whether individual-level health or behavioral interventions or place-level, systemic or policy interventions to reduce population burden will be most effective in reducing inequities in neurologic disease and outcomes. Although numerous clinical trials have focused on addressing downstream SDOH such as health literacy and health behaviors (e.g., medication adherence, physical activity, diet), few have addressed upstream, structural determinants which may have a more profound impact on addressing inequities in neurologic disease. Ultimately, further research is needed to determine which specific SDOH should be targeted and how, when, and by whom they should be addressed to improve neurologic outcomes.
MeSH term(s)	Humans ; Social Determinants of Health ; Nervous System Diseases/diagnosis ; Nervous System Diseases/epidemiology ; Educational Status ; Behavior Therapy ; Cognition
Language	English
Publishing date	2023-08-14
Publishing country	United States
Document type	Journal Article
ZDB-ID	207147-2
ISSN	1526-632X ; 0028-3878
ISSN (online)	1526-632X
ISSN	0028-3878
DOI	10.1212/WNL.0000000000207562
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Article ; Online: Longitudinal decline in semantic

Fernández, Kayri K / Kociolek, Anton J / Lao, Patrick J / Stern, Yaakov / Manly, Jennifer J / Vonk, Jet M J

Journal of the International Neuropsychological Society : JINS

2023 Volume 29, Issue 8, Page(s) 775–782

Abstract: Objective: To compare longitudinal verbal fluency performance among Latinx Spanish speakers who develop Alzheimer's disease to those who do not develop dementia in absolute number of words produced on each task and their ratio to combine both scores.: ...

Abstract	Objective: To compare longitudinal verbal fluency performance among Latinx Spanish speakers who develop Alzheimer's disease to those who do not develop dementia in absolute number of words produced on each task and their ratio to combine both scores. Method: Participants included 833 Latinx Spanish-speaking older adults from a community-based prospective cohort in Manhattan. We performed growth curve modeling to investigate the trajectories of letter and semantic fluency, and their ratio (i.e., 'semantic index'), between individuals who developed Alzheimer's disease and those who did not (i.e., controls). The semantic index quantifies the proportion of words generated for semantic fluency in relation to the total verbal fluency performance. Results: Letter fluency performance did not decline in controls; we observed a linear decline in those who developed Alzheimer's disease. Semantic fluency declined in both groups and showed an increased rate of change over time in the incident Alzheimer's disease group; in comparison, the control group had a linear and slower decline. There were no group differences in the longitudinal trajectory (intercept and slope) of the semantic index. Conclusion: A decline in letter fluency and a more rapid and accelerating decline over time in semantic fluency distinguished people who developed Alzheimer's disease from controls. Using the semantic index was not a superior marker of incident Alzheimer's disease compared to examining the two fluency scores individually. Results suggest the differential decline in verbal fluency tasks, when evaluated appropriately, may be useful for early identification of Alzheimer's disease in Latinx Spanish speakers, a historically understudied population.
MeSH term(s)	Aged ; Humans ; Alzheimer Disease/complications ; Alzheimer Disease/epidemiology ; Hispanic or Latino ; Neuropsychological Tests ; Prospective Studies ; Semantics ; Verbal Behavior ; Speech Disorders/diagnosis ; Speech Disorders/etiology
Language	English
Publishing date	2023-01-13
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1230632-0
ISSN	1469-7661 ; 1355-6177
ISSN (online)	1469-7661
ISSN	1355-6177
DOI	10.1017/S1355617722000856
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Article ; Online: Risk of Alzheimer's disease is associated with longitudinal changes in plasma biomarkers in the multi-ethnic Washington Heights-Hamilton Heights-Inwood Columbia Aging Project (WHICAP) cohort.

Gu, Yian / Honig, Lawrence S / Kang, Min Suk / Bahl, Aanya / Sanchez, Danurys / Reyes-Dumeyer, Dolly / Manly, Jennifer J / Dage, Jeffrey L / Lantigua, Rafael A / Brickman, Adam M / Vardarajan, Badri N / Mayeux, Richard

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

2024 Volume 20, Issue 3, Page(s) 1988–1999

Abstract: Background: Alzheimer's disease (AD) biomarkers can help differentiate cognitively unimpaired (CU) individuals from mild cognitive impairment (MCI) and dementia. The role of AD biomarkers in predicting cognitive impairment and AD needs examination.: ... ...

Abstract	Background: Alzheimer's disease (AD) biomarkers can help differentiate cognitively unimpaired (CU) individuals from mild cognitive impairment (MCI) and dementia. The role of AD biomarkers in predicting cognitive impairment and AD needs examination. Methods: In 628 CU individuals from a multi-ethnic cohort, amyloid beta (Aβ)42, Aβ40, phosphorylated tau-181 (p-tau181), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL) were measured in plasma. Results: Higher baseline levels of p-tau181/Aβ42 ratio were associated with an increased risk of incident dementia. A biomarker pattern (with elevated Aβ42/Aβ40 but low p-tau181/Aβ42) was associated with decreased dementia risk. Compared to CU, participants who developed MCI or dementia had a rapid decrease in this protective biomarker pattern reflecting AD-specific pathological change. Discussion: Elevated levels of AD biomarker p-tau181/Aβ42, by itself or combined with a low Aβ42/Aβ40 level, predicts clinically diagnosed AD. Individuals with a rapid change in these biomarkers may need close monitoring for the potential downward trajectory of cognition. Highlights: We discuss a multi-ethnic, urban community study of elderly individuals. The study consisted of a longitudinal assessment over 6 years with repeated clinical assessments. The study used blood-based biomarkers as predictors of mild cognitive impairment and Alzheimer's disease.
MeSH term(s)	Humans ; Aged ; Alzheimer Disease ; Amyloid beta-Peptides ; Washington ; tau Proteins ; Cognitive Dysfunction/diagnosis ; Aging ; Biomarkers
Chemical Substances	Amyloid beta-Peptides ; tau Proteins ; Biomarkers
Language	English
Publishing date	2024-01-06
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.13652
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