Subjective hearing loss (SHL) refers to an individual’s self-assessment of their hearing loss. The association and underlying mechanisms between SHL and cognitive impairment still necessitate elucidation.
Objectives
To validate potential mechanisms between SHL and cognitive impairment.
Design
Cross-section.
Setting
Shanghai, China.
Participants
A total of 2369 individuals from communities and the cognitive disorder clinic.
Measurements
All participants were subjected to a comprehensive neuropsychological assessment, encompassing the Hearing Handicap Inventory for the Elderly-Screening Version (HHIE-S). The participants’ brain β-amyloid (Aβ) deposition status, plasma biomarkers associated with Alzheimer’s disease (AD), and cardiovascular risk factors were also collected.
Results
In individuals with a heightened SHL, elevated HHIE-S score was linked to diminished cognitive and daily functioning as well as heightened levels of depressed mood. This correlation was observed in auditory memory performance but not in visual memory. The influence of SHL on cognitive function was mediated by depressed mood. SHL was associated with diabetes and smoking, whereas cognitive function was associated with hyperlipidemia and alcohol consumption. In individuals with positive brain Aβ deposition, SHL demonstrated associations with cognitive function independent of plasma Aβ42/40 ratio, P-tau181, neurofilament light chain, and APOE allele status.
Conclusion
SHL has an independent effect on cognitive impairment. The findings do no provide evidence for the common cause mechanism. Instead, the findings support the presence of a cognitive resource mechanism and an impoverished environment mechanism, along with the potential for a pathological interaction mechanism.
{"title":"Associations and Potential Multiple Mechanisms between Subjective Hearing Loss and Cognitive Impairment","authors":"","doi":"10.14283/jpad.2024.62","DOIUrl":"https://doi.org/10.14283/jpad.2024.62","url":null,"abstract":"<h3>Abstract</h3> <span> <h3>Background</h3> <p>Subjective hearing loss (SHL) refers to an individual’s self-assessment of their hearing loss. The association and underlying mechanisms between SHL and cognitive impairment still necessitate elucidation.</p> </span> <span> <h3>Objectives</h3> <p>To validate potential mechanisms between SHL and cognitive impairment.</p> </span> <span> <h3>Design</h3> <p>Cross-section.</p> </span> <span> <h3>Setting</h3> <p>Shanghai, China.</p> </span> <span> <h3>Participants</h3> <p>A total of 2369 individuals from communities and the cognitive disorder clinic.</p> </span> <span> <h3>Measurements</h3> <p>All participants were subjected to a comprehensive neuropsychological assessment, encompassing the Hearing Handicap Inventory for the Elderly-Screening Version (HHIE-S). The participants’ brain β-amyloid (Aβ) deposition status, plasma biomarkers associated with Alzheimer’s disease (AD), and cardiovascular risk factors were also collected.</p> </span> <span> <h3>Results</h3> <p>In individuals with a heightened SHL, elevated HHIE-S score was linked to diminished cognitive and daily functioning as well as heightened levels of depressed mood. This correlation was observed in auditory memory performance but not in visual memory. The influence of SHL on cognitive function was mediated by depressed mood. SHL was associated with diabetes and smoking, whereas cognitive function was associated with hyperlipidemia and alcohol consumption. In individuals with positive brain Aβ deposition, SHL demonstrated associations with cognitive function independent of plasma Aβ42/40 ratio, P-tau181, neurofilament light chain, and APOE allele status.</p> </span> <span> <h3>Conclusion</h3> <p>SHL has an independent effect on cognitive impairment. The findings do no provide evidence for the common cause mechanism. Instead, the findings support the presence of a cognitive resource mechanism and an impoverished environment mechanism, along with the potential for a pathological interaction mechanism.</p> </span>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"18 1","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140147158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cognitive reserve (CR) contributes to preserving cognition when facing brain aging and damage. CR has been linked to dementia risk in late life. However, the association between CR and cognitive changes and brain imaging measures, especially in midlife, is unclear.
Objective
We aimed to explore the association of CR with cognitive decline and structural brain differences in middle and older age.
Design
This longitudinal study was from the UK Biobank project where participants completed baseline surveys between 2006 to 2010 and were followed (mean follow-up: 9 years).
Setting
A population-based study.
Participants
A total of 42,301 dementia-free participants aged 40–70 were followed-up to detect cognitive changes. A subsample (n=34,041) underwent brain magnetic resonance imaging scans.
Measurements
We used latent class analysis to generate a CR indicator (categorized as high, moderate, and low) based on education, occupation, and multiple cognitively stimulating activities. Cognitive tests for global and domain-specific cognition were administrated at baseline and follow-up. Total brain, white matter, grey matter, hippocampal, and white matter hyperintensity volumes (TBV, WMV, GMV, HV, and WMHV) were assessed at the follow-up examination. Data were analyzed using mixed-effects models and analysis of covariance.
Results
At baseline, 16,032 (37.9%), 10,709 (25.3%), and 15,560 (36.8%) participants had low, moderate, and high levels of CR, respectively. Compared with low CR, high CR was associated with slower declines in global cognition (β [95% confidence interval]: 0.10 [0.08, 0.11]), prospective memory (0.10 [0.06, 0.15]), fluid intelligence (0.07 [0.04, 0.10]), and reaction time (0.04 [0.02, 0.06]). Participants with high CR had lower TBV, WMV, GMV, and WMHV, but higher HV when controlling for global cognition (corrected P <0.01 for all). The significant relationships between CR and cognition and TBV were present among both middle-aged (<60 years) and older (≥60 years) participants. The CR-cognition association remained significant despite reductions in brain structural properties.
Conclusions
Higher CR is associated with slower cognitive decline, higher HV, and lower microvascular burden, especially in middle age. Individuals with high CR could tolerate smaller brain volumes while maintaining cognition. The benefit of CR for cognition is independent of structural brain differences. Our findings highlight the contribution of enhancing CR to helping compensate for neuroimaging alterations and ultimately prevent cognitive decline.
{"title":"Association of Cognitive Reserve Indicator with Cognitive Decline and Structural Brain Differences in Middle and Older Age: Findings from the UK Biobank","authors":"","doi":"10.14283/jpad.2024.54","DOIUrl":"https://doi.org/10.14283/jpad.2024.54","url":null,"abstract":"<h3>Abstract</h3> <span> <h3>Background</h3> <p>Cognitive reserve (CR) contributes to preserving cognition when facing brain aging and damage. CR has been linked to dementia risk in late life. However, the association between CR and cognitive changes and brain imaging measures, especially in midlife, is unclear.</p> </span> <span> <h3>Objective</h3> <p>We aimed to explore the association of CR with cognitive decline and structural brain differences in middle and older age.</p> </span> <span> <h3>Design</h3> <p>This longitudinal study was from the UK Biobank project where participants completed baseline surveys between 2006 to 2010 and were followed (mean follow-up: 9 years).</p> </span> <span> <h3>Setting</h3> <p>A population-based study.</p> </span> <span> <h3>Participants</h3> <p>A total of 42,301 dementia-free participants aged 40–70 were followed-up to detect cognitive changes. A subsample (n=34,041) underwent brain magnetic resonance imaging scans.</p> </span> <span> <h3>Measurements</h3> <p>We used latent class analysis to generate a CR indicator (categorized as high, moderate, and low) based on education, occupation, and multiple cognitively stimulating activities. Cognitive tests for global and domain-specific cognition were administrated at baseline and follow-up. Total brain, white matter, grey matter, hippocampal, and white matter hyperintensity volumes (TBV, WMV, GMV, HV, and WMHV) were assessed at the follow-up examination. Data were analyzed using mixed-effects models and analysis of covariance.</p> </span> <span> <h3>Results</h3> <p>At baseline, 16,032 (37.9%), 10,709 (25.3%), and 15,560 (36.8%) participants had low, moderate, and high levels of CR, respectively. Compared with low CR, high CR was associated with slower declines in global cognition (β [95% confidence interval]: 0.10 [0.08, 0.11]), prospective memory (0.10 [0.06, 0.15]), fluid intelligence (0.07 [0.04, 0.10]), and reaction time (0.04 [0.02, 0.06]). Participants with high CR had lower TBV, WMV, GMV, and WMHV, but higher HV when controlling for global cognition (corrected P <0.01 for all). The significant relationships between CR and cognition and TBV were present among both middle-aged (<60 years) and older (≥60 years) participants. The CR-cognition association remained significant despite reductions in brain structural properties.</p> </span> <span> <h3>Conclusions</h3> <p>Higher CR is associated with slower cognitive decline, higher HV, and lower microvascular burden, especially in middle age. Individuals with high CR could tolerate smaller brain volumes while maintaining cognition. The benefit of CR for cognition is independent of structural brain differences. Our findings highlight the contribution of enhancing CR to helping compensate for neuroimaging alterations and ultimately prevent cognitive decline.</p> </span>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"5 1","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140146996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Novel plasma biomarkers are promising for identifying Alzheimer’s disease (AD) pathological processes in vivo, but most currently employed assays have limitations precluding widespread use.
Methods
CSF and plasma samples were collected from seventy amnestic mild cognitive impairment (aMCI) subjects, stratified as A+ and A−. CSF Aβ40, Aβ42, p-tau181 and t-tau and plasma Aβ40, Aβ42 and p-tau181 quantification were conducted using the Lumipulse G assays (Fujirebio), to evaluate the diagnostic performance of plasma biomarkers and assess their associations with CSF biomarkers.
Results
All plasma biomarkers except Aβ40 showed a very good accuracy in distinguishing A+ aMCI from A− aMCI, Aβ42/p-tau181 ratio being the most accurate (AUC 0.895, sensitivity 95.1%, specificity 82.8%). Plasma biomarkers levels were significantly associated with CSF biomarkers concentration.
Discussion
High-throughput and fully-automated plasma assays could be helpful in discriminating with high accuracy between aMCI in the AD continuum and aMCI unlikely due to AD in clinical settings.
{"title":"Performance of Fully-Automated High-Throughput Plasma Biomarker Assays for Alzheimer’s Disease in Amnestic Mild Cognitive Impairment Subjects","authors":"","doi":"10.14283/jpad.2024.58","DOIUrl":"https://doi.org/10.14283/jpad.2024.58","url":null,"abstract":"<h3>Abstract</h3> <span> <h3>Introduction</h3> <p>Novel plasma biomarkers are promising for identifying Alzheimer’s disease (AD) pathological processes in vivo, but most currently employed assays have limitations precluding widespread use.</p> </span> <span> <h3>Methods</h3> <p>CSF and plasma samples were collected from seventy amnestic mild cognitive impairment (aMCI) subjects, stratified as A+ and A−. CSF Aβ40, Aβ42, p-tau181 and t-tau and plasma Aβ40, Aβ42 and p-tau181 quantification were conducted using the Lumipulse G assays (Fujirebio), to evaluate the diagnostic performance of plasma biomarkers and assess their associations with CSF biomarkers.</p> </span> <span> <h3>Results</h3> <p>All plasma biomarkers except Aβ40 showed a very good accuracy in distinguishing A+ aMCI from A− aMCI, Aβ42/p-tau181 ratio being the most accurate (AUC 0.895, sensitivity 95.1%, specificity 82.8%). Plasma biomarkers levels were significantly associated with CSF biomarkers concentration.</p> </span> <span> <h3>Discussion</h3> <p>High-throughput and fully-automated plasma assays could be helpful in discriminating with high accuracy between aMCI in the AD continuum and aMCI unlikely due to AD in clinical settings.</p> </span>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"14 1","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140147274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Haiyan Liu, J. Li, E. Ziegemeier, S. Adams, E. McDade, D. B. Clifford, Y. Cao, G. Wang, Y. Li, S. L. Mills, A. M. Santacruz, S. Belyew, J. D. Grill, B. J. Snider, C. J. Mummery, G. Surti, D. Hannequin, D. Wallon, S. B. Berman, I. Z. Jimenez-Velazquez, E. D. Roberson, C. H. van Dyck, L. S. Honig, R. Sanchez-Valle, W. S. Brooks, S. Gauthier, D. Galasko, C. L. Masters, J. Brosch, G.-Y. R. Hsiung, S. Jayadev, M. Formaglio, M. Masellis, R. Clarnette, J. Pariente, B. Dubois, F. Pasquier, R. J. Bateman, Jorge J. Llibre-Guerra
Background
Clinical trial satisfaction is increasingly important for future trial designs and is associated with treatment adherence and willingness to enroll in future research studies or to recommend trial participation. In this post-trial survey, we examined participant satisfaction and attitudes toward future clinical trials in the Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU).
Methods
We developed an anonymous, participant satisfaction survey tailored to participants enrolled in the DIAN-TU-001 double-blind clinical trial of solanezumab or gantenerumab and requested that all study sites share the survey with their trial participants. A total of 194 participants enrolled in the trial at 24 study sites. We utilized regression analysis to explore the link between participants’ clinical trial experiences, their satisfaction, and their willingness to participate in upcoming trials.
Results
Survey responses were received over a sixteen-month window during 2020–2021 from 58 participants representing 15 study sites. Notably, 96.5% of the survey respondents expressed high levels of satisfaction with the trial, 91.4% would recommend trial participation, and 96.5% were willing to enroll again. Age, gender, and education did not influence satisfaction levels. Participants reported enhanced medical care (70.7%) and pride in contributing to the DIAN-TU trial (84.5%). Satisfaction with personnel and procedures was high (98.3%). Respondents had a mean age of 48.7 years, with most being from North America and Western Europe, matching the trial’s demographic distribution. Participants’ decisions to learn their genetic status increased during the trial, and most participants endorsed considering future trial participation regardless of the DIAN-TU-001 trial outcome.
Conclusion
Results suggest that DIAN-TU-001 participants who responded to the survey exhibited high motivation to participate in research, overall satisfaction with the clinical trial, and willingness to participate in research in the future, despite a long trial duration of 4–7 years with detailed annual clinical, cognitive, PET, MRI, and lumbar puncture assessments. Implementation of features that alleviate barriers and challenges to trial participation is like to have a high impact on trial satisfaction and reduce participant burden.
{"title":"Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU): Trial Satisfaction and Attitudes towards Future Clinical Trials","authors":"Haiyan Liu, J. Li, E. Ziegemeier, S. Adams, E. McDade, D. B. Clifford, Y. Cao, G. Wang, Y. Li, S. L. Mills, A. M. Santacruz, S. Belyew, J. D. Grill, B. J. Snider, C. J. Mummery, G. Surti, D. Hannequin, D. Wallon, S. B. Berman, I. Z. Jimenez-Velazquez, E. D. Roberson, C. H. van Dyck, L. S. Honig, R. Sanchez-Valle, W. S. Brooks, S. Gauthier, D. Galasko, C. L. Masters, J. Brosch, G.-Y. R. Hsiung, S. Jayadev, M. Formaglio, M. Masellis, R. Clarnette, J. Pariente, B. Dubois, F. Pasquier, R. J. Bateman, Jorge J. Llibre-Guerra","doi":"10.14283/jpad.2024.61","DOIUrl":"https://doi.org/10.14283/jpad.2024.61","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Clinical trial satisfaction is increasingly important for future trial designs and is associated with treatment adherence and willingness to enroll in future research studies or to recommend trial participation. In this post-trial survey, we examined participant satisfaction and attitudes toward future clinical trials in the Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU).</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>We developed an anonymous, participant satisfaction survey tailored to participants enrolled in the DIAN-TU-001 double-blind clinical trial of solanezumab or gantenerumab and requested that all study sites share the survey with their trial participants. A total of 194 participants enrolled in the trial at 24 study sites. We utilized regression analysis to explore the link between participants’ clinical trial experiences, their satisfaction, and their willingness to participate in upcoming trials.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Survey responses were received over a sixteen-month window during 2020–2021 from 58 participants representing 15 study sites. Notably, 96.5% of the survey respondents expressed high levels of satisfaction with the trial, 91.4% would recommend trial participation, and 96.5% were willing to enroll again. Age, gender, and education did not influence satisfaction levels. Participants reported enhanced medical care (70.7%) and pride in contributing to the DIAN-TU trial (84.5%). Satisfaction with personnel and procedures was high (98.3%). Respondents had a mean age of 48.7 years, with most being from North America and Western Europe, matching the trial’s demographic distribution. Participants’ decisions to learn their genetic status increased during the trial, and most participants endorsed considering future trial participation regardless of the DIAN-TU-001 trial outcome.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>Results suggest that DIAN-TU-001 participants who responded to the survey exhibited high motivation to participate in research, overall satisfaction with the clinical trial, and willingness to participate in research in the future, despite a long trial duration of 4–7 years with detailed annual clinical, cognitive, PET, MRI, and lumbar puncture assessments. Implementation of features that alleviate barriers and challenges to trial participation is like to have a high impact on trial satisfaction and reduce participant burden.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"44 1","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140147013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
D. Gao, W. Rong, C. Li, J. Liang, Y. Wang, Y. Pan, W. Zhang, Fanfan Zheng, Wuxiang Xie
Background
A history of fracture has been associated with increased risk of dementia; however, it is uncertain whether sex difference exists in the association between prior fracture and subsequent risk of incident dementia.
Objectives
To investigate whether sex modified the relationship between prior fracture and subsequent risk of dementia.
Design
Prospective cohort study.
Setting
UK Biobank.
Participants
496,331 participants (54.6% women) free of dementia at baseline.
Measurements
History of fracture was self-reported via touchscreen questionnaires at baseline. The primary outcome was all-cause dementia.
Results
Both any fracture and fragility fracture were significantly associated with an increased risk of subsequent all-cause dementia in men (adjusted hazard ratio (HR): 1.28; 95% confidence interval (CI): 1.14–1.43; adjusted HR: 1.48; 95% CI: 1.18–1.87, respectively), but not in women (adjusted HR: 1.04; 95% CI 0.95–1.15; adjusted HR: 1.01; 95% CI: 0.87–1.18, respectively); and these sex-differences were significant (P interaction = 0.006; P interaction = 0.007, respectively). The sex differences in the impacts of different fracture sites (including upper limb, lower limb, spine, and multiple sites) were consistent on all-cause dementia.
Conclusions
This study demonstrated that prior fracture was associated with an increased risk of dementia in men but not in women, and the sex difference was significant. Previous fracture may be an important marker for identifying subsequent dementia in middle-aged and older men.
{"title":"Sex Difference in the Association between Prior Fracture and Subsequent Risk of Incident Dementia: A Longitudinal Cohort Study","authors":"D. Gao, W. Rong, C. Li, J. Liang, Y. Wang, Y. Pan, W. Zhang, Fanfan Zheng, Wuxiang Xie","doi":"10.14283/jpad.2024.56","DOIUrl":"https://doi.org/10.14283/jpad.2024.56","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>A history of fracture has been associated with increased risk of dementia; however, it is uncertain whether sex difference exists in the association between prior fracture and subsequent risk of incident dementia.</p><h3 data-test=\"abstract-sub-heading\">Objectives</h3><p>To investigate whether sex modified the relationship between prior fracture and subsequent risk of dementia.</p><h3 data-test=\"abstract-sub-heading\">Design</h3><p>Prospective cohort study.</p><h3 data-test=\"abstract-sub-heading\">Setting</h3><p>UK Biobank.</p><h3 data-test=\"abstract-sub-heading\">Participants</h3><p>496,331 participants (54.6% women) free of dementia at baseline.</p><h3 data-test=\"abstract-sub-heading\">Measurements</h3><p>History of fracture was self-reported via touchscreen questionnaires at baseline. The primary outcome was all-cause dementia.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Both any fracture and fragility fracture were significantly associated with an increased risk of subsequent all-cause dementia in men (adjusted hazard ratio (HR): 1.28; 95% confidence interval (CI): 1.14–1.43; adjusted HR: 1.48; 95% CI: 1.18–1.87, respectively), but not in women (adjusted HR: 1.04; 95% CI 0.95–1.15; adjusted HR: 1.01; 95% CI: 0.87–1.18, respectively); and these sex-differences were significant (P interaction = 0.006; P interaction = 0.007, respectively). The sex differences in the impacts of different fracture sites (including upper limb, lower limb, spine, and multiple sites) were consistent on all-cause dementia.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>This study demonstrated that prior fracture was associated with an increased risk of dementia in men but not in women, and the sex difference was significant. Previous fracture may be an important marker for identifying subsequent dementia in middle-aged and older men.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"21 1","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140072600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Samuel Dickson, A. Solomon, M. Kivipelto, T. Hartmann, A. M. J. van Hees, A. Brownlee, B. Haaland, C. H. Mallinckrodt, S. B. Hendrix
Assessment of meaningfulness in randomized clinical trials (RCTs) in Alzheimer’s disease (AD) is challenging, particularly in early disease. Converting clinical outcomes to disease progression time allows assessment of treatment effects using a metric that is understandable and meaningful: time. We demonstrate time savings assessments using meta time component tests (TCTs) in the LipiDiDiet multinutrient RCT. Dietary patterns are important for dementia prevention, likely due to individual cumulative nutrient effects. LipiDiDiet used a multinutrient (Fortasyn Connect) formulation in patients with prodromal AD, benefitting cognition (5-item composite NTB, effect 0.089), cognition and function (CDR-SB, −0.605), and slowing hippocampal atrophy (0.122 cm3). Meaningfulness of point differences is unclear. However, a combination TCT showed 9-month disease time savings at 24 months (38% slowing of disease time): 9.0, 10.5, and 7.2 months for NTB, CDR-SB, and hippocampal volume, underscoring the value of TCTs in AD RCTs and the need for continued validation of this approach.
{"title":"Evaluation of Clinical Meaningfulness of Fortasyn Connect in Terms of “Time Saved”","authors":"Samuel Dickson, A. Solomon, M. Kivipelto, T. Hartmann, A. M. J. van Hees, A. Brownlee, B. Haaland, C. H. Mallinckrodt, S. B. Hendrix","doi":"10.14283/jpad.2024.55","DOIUrl":"https://doi.org/10.14283/jpad.2024.55","url":null,"abstract":"<p>Assessment of meaningfulness in randomized clinical trials (RCTs) in Alzheimer’s disease (AD) is challenging, particularly in early disease. Converting clinical outcomes to disease progression time allows assessment of treatment effects using a metric that is understandable and meaningful: time. We demonstrate time savings assessments using meta time component tests (TCTs) in the LipiDiDiet multinutrient RCT. Dietary patterns are important for dementia prevention, likely due to individual cumulative nutrient effects. LipiDiDiet used a multinutrient (Fortasyn Connect) formulation in patients with prodromal AD, benefitting cognition (5-item composite NTB, effect 0.089), cognition and function (CDR-SB, −0.605), and slowing hippocampal atrophy (0.122 cm<sup>3</sup>). Meaningfulness of point differences is unclear. However, a combination TCT showed 9-month disease time savings at 24 months (38% slowing of disease time): 9.0, 10.5, and 7.2 months for NTB, CDR-SB, and hippocampal volume, underscoring the value of TCTs in AD RCTs and the need for continued validation of this approach.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"2015 1","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140072317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Relationships of fish-shellfish consumption, cognitive health and mortality from Alzheimer’s disease (AD) among US adults aged 60 years and older have not been adequately studied.
Objectives
To determine the relationship of fish-shellfish consumption, cognitive health and mortality from AD in US adults aged 60 years and older.
Design, Setting and Participants
The data of this cross-sectional study of US adults aged 60 years and older were from the National Nutrition and Health Examination Survey (NHANES) datasets. Frequency of fish-shellfish consumption, its association with subjective cognitive decline (SCD) and AD mortality of these participants between 1999 and 2018 and cognitive assessment scores between 2011 and 2014 were analyzed.
Measurements and Results
US adults aged 60 years and older consumed fish-shellfish 1.2 times/week and had a blood Hg of 1.63 ug/L on average between 1999 and 2018. Participants aged 60 years and older in the highest quartile of fish-shellfish consumption (∼3 times/week) had significantly higher cognitive assessment scores than those in the lowest quartile (rare or no fish-shellfish consumption). Adults in the highest quartile of fish-shellfish consumption had a 30% lower risk (odds ratio 0.7, 95%CI 0.57–0.87) of SCD, and 44% lower risk (hazard ratio 0.56, 95%CI 0.35–0.9) of AD mortality than those in the lowest quartile.
Conclusion
Increased fish-shellfish consumption was associated with improved scores of cognitive assessment and reduced risks of SCD and AD mortality.
{"title":"Fish and Shellfish Consumption, Cognitive Health and Mortality from Alzheimer’s Disease among US Adults Aged 60 and Older","authors":"","doi":"10.14283/jpad.2024.57","DOIUrl":"https://doi.org/10.14283/jpad.2024.57","url":null,"abstract":"<h3>Abstract</h3> <span> <h3>Background</h3> <p>Relationships of fish-shellfish consumption, cognitive health and mortality from Alzheimer’s disease (AD) among US adults aged 60 years and older have not been adequately studied.</p> </span> <span> <h3>Objectives</h3> <p>To determine the relationship of fish-shellfish consumption, cognitive health and mortality from AD in US adults aged 60 years and older.</p> </span> <span> <h3>Design, Setting and Participants</h3> <p>The data of this cross-sectional study of US adults aged 60 years and older were from the National Nutrition and Health Examination Survey (NHANES) datasets. Frequency of fish-shellfish consumption, its association with subjective cognitive decline (SCD) and AD mortality of these participants between 1999 and 2018 and cognitive assessment scores between 2011 and 2014 were analyzed.</p> </span> <span> <h3>Measurements and Results</h3> <p>US adults aged 60 years and older consumed fish-shellfish 1.2 times/week and had a blood Hg of 1.63 ug/L on average between 1999 and 2018. Participants aged 60 years and older in the highest quartile of fish-shellfish consumption (∼3 times/week) had significantly higher cognitive assessment scores than those in the lowest quartile (rare or no fish-shellfish consumption). Adults in the highest quartile of fish-shellfish consumption had a 30% lower risk (odds ratio 0.7, 95%CI 0.57–0.87) of SCD, and 44% lower risk (hazard ratio 0.56, 95%CI 0.35–0.9) of AD mortality than those in the lowest quartile.</p> </span> <span> <h3>Conclusion</h3> <p>Increased fish-shellfish consumption was associated with improved scores of cognitive assessment and reduced risks of SCD and AD mortality.</p> </span>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"149 1","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140204439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. N. Temedda, A. Garnier-Crussard, C. Mouchoux, Virginie Dauphinot
This systematic review aimed to examine whether higher comorbidity burden, as assessed by comorbidity indices, was associated with a functional autonomy decline in individuals with cognitive impairment. The search was conducted in the following databases: PubMed/MEDLINE, ScienceDirect, Cochrane, and Embase. Both cross-sectional and longitudinal studies that examined the relationship between comorbidity indices and scales measuring activities of daily living (ADL) in individuals with cognitive impairment were included. The quality assessment tool for observational cohort and cross-sectional studies of the National Institutes of Health (NIH) was used. Overall, 12 studies were included, among which three were longitudinal. Significant association was frequently reported by cross-sectional designs (n=7 studies) and only one study reported a significant longitudinal association. This longitudinal study repeatedly assessed both comorbidity burden and functional autonomy, and considered comorbidity burden as a time-varying covariate. Considering comorbidity burden as a time varying covariate may deal with the dynamic nature of comorbidity burden over time, and conducting repeated assessments during the follow-up using both comorbidity index and ADL scales may increase their sensitivity to reliably measure comorbidity burden and functional autonomy decline over time. In conclusion, a higher comorbidity index was associated with a lower level of functional autonomy in people with cognitive impairment. This relationship seems to be dynamic over time and using comorbidity indices and ADL scales only once may not deal with the fluctuation of both comorbidity burden and functional autonomy decline. To cope with complexity of this relationship this review highlights some methodological approaches to be considered.
{"title":"Association between Comorbidity Indices and Functional Autonomy in Individuals with Cognitive Impairment: A Systematic Review","authors":"M. N. Temedda, A. Garnier-Crussard, C. Mouchoux, Virginie Dauphinot","doi":"10.14283/jpad.2024.51","DOIUrl":"https://doi.org/10.14283/jpad.2024.51","url":null,"abstract":"<p>This systematic review aimed to examine whether higher comorbidity burden, as assessed by comorbidity indices, was associated with a functional autonomy decline in individuals with cognitive impairment. The search was conducted in the following databases: PubMed/MEDLINE, ScienceDirect, Cochrane, and Embase. Both cross-sectional and longitudinal studies that examined the relationship between comorbidity indices and scales measuring activities of daily living (ADL) in individuals with cognitive impairment were included. The quality assessment tool for observational cohort and cross-sectional studies of the National Institutes of Health (NIH) was used. Overall, 12 studies were included, among which three were longitudinal. Significant association was frequently reported by cross-sectional designs (n=7 studies) and only one study reported a significant longitudinal association. This longitudinal study repeatedly assessed both comorbidity burden and functional autonomy, and considered comorbidity burden as a time-varying covariate. Considering comorbidity burden as a time varying covariate may deal with the dynamic nature of comorbidity burden over time, and conducting repeated assessments during the follow-up using both comorbidity index and ADL scales may increase their sensitivity to reliably measure comorbidity burden and functional autonomy decline over time. In conclusion, a higher comorbidity index was associated with a lower level of functional autonomy in people with cognitive impairment. This relationship seems to be dynamic over time and using comorbidity indices and ADL scales only once may not deal with the fluctuation of both comorbidity burden and functional autonomy decline. To cope with complexity of this relationship this review highlights some methodological approaches to be considered.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"69 1","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140019784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alzheimer’s disease (AD) is a neurodegenerative disease and there is by far no effective treatment for it, especially in its late stage. Circular RNAs (circRNAs), known as a class of non-coding RNAs are widely observed in eukaryotic transcriptomes, and are reported to play an important role in neurodegenerative diseases including AD. circRNAs usually act as microRNA (miRNA) inhibitors or «sponges» to regulate the function of miRNAs, leading to subsequent changes in protein activities and functions. Accumulating evidence indicates that circRNAs can serve as potential biomarker in AD early prediction. The functional roles of circRNAs are very versatile including miRNAs binding - thus affecting downstream gene expression, generating abnormally translated protein peptides, and affecting epigenetic modifications which subsequently affect AD related gene expressions. Therefore, identifying AD-related circRNAs can contribute to AD early diagnosis and intervention. In this work, we collected and curated an AD-related circRNA dataset; by exploring the circRNAs’ corresponding DNA loci distribution in chromatin 3D conformation (3D genome) and utilize the such 3D genome information, we were able to selected a concise yet predictively effective circRNA panel, based on which, significantly better AD prediction machine learning models were achieved.
{"title":"Prediction of Alzheimer’s Disease Based on 3D Genome Selected circRNA","authors":"","doi":"10.14283/jpad.2024.52","DOIUrl":"https://doi.org/10.14283/jpad.2024.52","url":null,"abstract":"<h3>Abstract</h3> <p>Alzheimer’s disease (AD) is a neurodegenerative disease and there is by far no effective treatment for it, especially in its late stage. Circular RNAs (circRNAs), known as a class of non-coding RNAs are widely observed in eukaryotic transcriptomes, and are reported to play an important role in neurodegenerative diseases including AD. circRNAs usually act as microRNA (miRNA) inhibitors or «sponges» to regulate the function of miRNAs, leading to subsequent changes in protein activities and functions. Accumulating evidence indicates that circRNAs can serve as potential biomarker in AD early prediction. The functional roles of circRNAs are very versatile including miRNAs binding - thus affecting downstream gene expression, generating abnormally translated protein peptides, and affecting epigenetic modifications which subsequently affect AD related gene expressions. Therefore, identifying AD-related circRNAs can contribute to AD early diagnosis and intervention. In this work, we collected and curated an AD-related circRNA dataset; by exploring the circRNAs’ corresponding DNA loci distribution in chromatin 3D conformation (3D genome) and utilize the such 3D genome information, we were able to selected a concise yet predictively effective circRNA panel, based on which, significantly better AD prediction machine learning models were achieved.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"1 1","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140019664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Y. Wang, D. Ren, J. S. Roberts, L. K. Tamres, J. H. Lingler
<h3 data-test="abstract-sub-heading">Background</h3><p>Growing evidence supports the clinical utility of amyloid PET, however, whether patients at risk for dementia use knowledge of their brain amyloid status to alter their health behaviors remains unclear.</p><h3 data-test="abstract-sub-heading">Objectives</h3><p>To explore the effect of amyloid PET results disclosure on self-reported health behaviors in patients with mild cognitive impairment.</p><h3 data-test="abstract-sub-heading">Design</h3><p>Self-reported health behaviors were a secondary outcome of the Return of Amyloid Imaging Scan Results (RAISR) randomized clinical trial of amyloid PET results disclosure for individuals with mild cognitive impairment.</p><h3 data-test="abstract-sub-heading">Setting</h3><p>Academic medical center.</p><h3 data-test="abstract-sub-heading">Participants</h3><p>RAISR study participants included 82 patients with mild cognitive impairment who were 92% non-Hispanic white, 59% male, and, on average, 73 ± 8.61 years old with 16.25 ± 2.49 years of education.</p><h3 data-test="abstract-sub-heading">Intervention</h3><p>Participants were assigned to a scan group with the opportunity to have an amyloid PET scan and learn their results or to a control group consisting only of a mild cognitive impairment education session and no opportunity for an amyloid PET scan.</p><h3 data-test="abstract-sub-heading">Measurements</h3><p>A 14-item health behavior questionnaire supplemented with qualitative data from the open-ended text entries to describe “other” health behaviors and follow-up semi-structured interviews. Baseline assessments were conducted prior to group assignment. For the present analysis, 71 participants had available data and scan group participants were divided by amyloid status, creating three groups for comparison: amyloid positive, amyloid negative, and control (no scan).</p><h3 data-test="abstract-sub-heading">Results</h3><p>Over 12 months of follow-up, no significant differences were observed in lifestyle, vitamin/supplement use, stress reduction activities, cognitive stimulation, or advance directive completion. Amyloid-negative participants were less likely than controls to consider long-term care insurance (63.6% vs. 89.2%; P =.025), and to endorse behaviors classified as “other” (36.4% vs. 64.9%; P = 0.037). After adjusting for education level, gender, and Mini-Mental State Exam score, logistic regression showed that amyloid-negative patients were 74% less likely than controls to report “other” behaviors (OR = 0.26, 95% CI [0.08, 0.85], P = 0.025), and 78% less likely to consider long-term care insurance (OR= 0.22, 95% CI [0.06, 0.86], P = 0.03). Qualitative analysis of open-ended questionnaire data and supplemental interviews with scan group participants revealed “other” activities to include changes in areas like employment, driving, and residential status, and engagement in other non-medical activities (e.g., pursuing bucket lists).</p><h3 data-test=
背景越来越多的证据支持淀粉样蛋白PET的临床应用，然而，痴呆症高危患者是否会利用大脑淀粉样蛋白状态的知识来改变自己的健康行为仍不清楚。目的探讨淀粉样蛋白PET结果公开对轻度认知障碍患者自我报告的健康行为的影响。设计自我报告的健康行为是淀粉样蛋白成像扫描结果回报（RAISR）随机临床试验的次要结果，该试验针对轻度认知障碍患者进行淀粉样蛋白 PET 结果披露。参与者RAISR研究参与者包括82名轻度认知障碍患者，其中92%为非西班牙裔白人，59%为男性，平均年龄为（73±8.61）岁，受教育年限为（16.25±2.49）年。干预措施参与者被分配到扫描组，该组有机会进行淀粉样蛋白 PET 扫描并了解扫描结果；或者被分配到对照组，该组只有轻度认知障碍教育课程，没有机会进行淀粉样蛋白 PET 扫描。在分组前进行了基线评估。结果在 12 个月的随访中，在生活方式、维生素/补充剂使用、减压活动、认知刺激或预先指示完成情况方面没有观察到显著差异。与对照组相比，淀粉样蛋白阴性的参与者不太可能考虑长期护理保险（63.6% 对 89.2%；P =0.025），也不太可能赞同被归类为 "其他 "的行为（36.4% 对 64.9%；P =0.037）。调整教育水平、性别和迷你精神状态检查得分后，逻辑回归显示淀粉样蛋白阴性患者报告 "其他 "行为的可能性比对照组低 74%（OR=0.26，95% CI [0.08，0.85]，P=0.025），考虑长期护理保险的可能性低 78%（OR=0.22，95% CI [0.06，0.86]，P=0.03）。对开放式问卷数据的定性分析以及对扫描组参与者的补充访谈显示，"其他 "活动包括就业、驾驶和居住状况等方面的变化，以及参与其他非医疗活动（如追求遗愿清单）。结论这项对淀粉样蛋白PET披露后健康相关行为变化的探索性分析表明，了解一个人大脑淀粉样蛋白状态的价值可能因扫描结果而异，并包括更注重最大限度提高生活质量而非促进认知健康的行动。
{"title":"Value of Knowing: Health-Related Behavior Changes following Amyloid PET Results Disclosure in Mild Cognitive Impairment","authors":"Y. Wang, D. Ren, J. S. Roberts, L. K. Tamres, J. H. Lingler","doi":"10.14283/jpad.2024.50","DOIUrl":"https://doi.org/10.14283/jpad.2024.50","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Growing evidence supports the clinical utility of amyloid PET, however, whether patients at risk for dementia use knowledge of their brain amyloid status to alter their health behaviors remains unclear.</p><h3 data-test=\"abstract-sub-heading\">Objectives</h3><p>To explore the effect of amyloid PET results disclosure on self-reported health behaviors in patients with mild cognitive impairment.</p><h3 data-test=\"abstract-sub-heading\">Design</h3><p>Self-reported health behaviors were a secondary outcome of the Return of Amyloid Imaging Scan Results (RAISR) randomized clinical trial of amyloid PET results disclosure for individuals with mild cognitive impairment.</p><h3 data-test=\"abstract-sub-heading\">Setting</h3><p>Academic medical center.</p><h3 data-test=\"abstract-sub-heading\">Participants</h3><p>RAISR study participants included 82 patients with mild cognitive impairment who were 92% non-Hispanic white, 59% male, and, on average, 73 ± 8.61 years old with 16.25 ± 2.49 years of education.</p><h3 data-test=\"abstract-sub-heading\">Intervention</h3><p>Participants were assigned to a scan group with the opportunity to have an amyloid PET scan and learn their results or to a control group consisting only of a mild cognitive impairment education session and no opportunity for an amyloid PET scan.</p><h3 data-test=\"abstract-sub-heading\">Measurements</h3><p>A 14-item health behavior questionnaire supplemented with qualitative data from the open-ended text entries to describe “other” health behaviors and follow-up semi-structured interviews. Baseline assessments were conducted prior to group assignment. For the present analysis, 71 participants had available data and scan group participants were divided by amyloid status, creating three groups for comparison: amyloid positive, amyloid negative, and control (no scan).</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Over 12 months of follow-up, no significant differences were observed in lifestyle, vitamin/supplement use, stress reduction activities, cognitive stimulation, or advance directive completion. Amyloid-negative participants were less likely than controls to consider long-term care insurance (63.6% vs. 89.2%; P =.025), and to endorse behaviors classified as “other” (36.4% vs. 64.9%; P = 0.037). After adjusting for education level, gender, and Mini-Mental State Exam score, logistic regression showed that amyloid-negative patients were 74% less likely than controls to report “other” behaviors (OR = 0.26, 95% CI [0.08, 0.85], P = 0.025), and 78% less likely to consider long-term care insurance (OR= 0.22, 95% CI [0.06, 0.86], P = 0.03). Qualitative analysis of open-ended questionnaire data and supplemental interviews with scan group participants revealed “other” activities to include changes in areas like employment, driving, and residential status, and engagement in other non-medical activities (e.g., pursuing bucket lists).</p><h3 data-test=","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"2 1","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140019534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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