Pub Date : 2023-10-01Epub Date: 2023-10-30DOI: 10.1097/WAD.0000000000000591
Annalise Rahman-Filipiak, Mary Lesniak, Shima Sadaghiyani, Scott Roberts, Peter Lichtenberg, Benjamin M Hampstead
Purpose: Alzheimer disease (AD) biomarker testing is now common in research and approaching clinical translation. Disclosure protocols must be informed by diverse participants' perspectives on if/how the information would be useful.
Methods: This study utilized semistructured interviews assessing interest in receiving positron emission tomography (PET) amyloid and tau results, as well as perceived risks and benefits of hypothetical PET disclosure as a function of race and participant diagnosis.
Participants: Participants [39% Black; 61% White; Mage =74.28 (5.98)] included 57 adults diagnosed as either cognitively healthy (58%) or with mild cognitive impairment (42%) and their respective care partners [33% Black; 67% White; Mage =66.93 (10.92)].
Results: Most dyads endorsed strong interest in PET results (82.5% of both participants and partners) regardless of race or diagnosis. Black care partners were less interested in receiving the participant's results than White care partners ( χ2(4) =8.31, P =0.047). Reasons for disclosure were diverse and highly personalized, including access to treatments or clinical trials (23.2% participants; 29.8% partners), advance planning (14.3% participants; 17.5% partners), and improved health knowledge (12.5% participants; 15.8% partners). In contrast, over 80% of respondents denied any risks of disclosure.
Discussion: Results suggest that predisclosure education, decisional capacity assessment, and a flexible disclosure approach are needed.
{"title":"Perspectives From Black and White Participants and Care Partners on Return of Amyloid and Tau PET Imaging and Other Research Results.","authors":"Annalise Rahman-Filipiak, Mary Lesniak, Shima Sadaghiyani, Scott Roberts, Peter Lichtenberg, Benjamin M Hampstead","doi":"10.1097/WAD.0000000000000591","DOIUrl":"10.1097/WAD.0000000000000591","url":null,"abstract":"<p><strong>Purpose: </strong>Alzheimer disease (AD) biomarker testing is now common in research and approaching clinical translation. Disclosure protocols must be informed by diverse participants' perspectives on if/how the information would be useful.</p><p><strong>Methods: </strong>This study utilized semistructured interviews assessing interest in receiving positron emission tomography (PET) amyloid and tau results, as well as perceived risks and benefits of hypothetical PET disclosure as a function of race and participant diagnosis.</p><p><strong>Participants: </strong>Participants [39% Black; 61% White; Mage =74.28 (5.98)] included 57 adults diagnosed as either cognitively healthy (58%) or with mild cognitive impairment (42%) and their respective care partners [33% Black; 67% White; Mage =66.93 (10.92)].</p><p><strong>Results: </strong>Most dyads endorsed strong interest in PET results (82.5% of both participants and partners) regardless of race or diagnosis. Black care partners were less interested in receiving the participant's results than White care partners ( χ2(4) =8.31, P =0.047). Reasons for disclosure were diverse and highly personalized, including access to treatments or clinical trials (23.2% participants; 29.8% partners), advance planning (14.3% participants; 17.5% partners), and improved health knowledge (12.5% participants; 15.8% partners). In contrast, over 80% of respondents denied any risks of disclosure.</p><p><strong>Discussion: </strong>Results suggest that predisclosure education, decisional capacity assessment, and a flexible disclosure approach are needed.</p>","PeriodicalId":7679,"journal":{"name":"Alzheimer Disease & Associated Disorders","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10664783/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"61559834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-10-01Epub Date: 2023-11-28DOI: 10.1097/WAD.0000000000000592
Lawrence S Honig
{"title":"Alzheimer Disease: A New Beginning in Therapeutics.","authors":"Lawrence S Honig","doi":"10.1097/WAD.0000000000000592","DOIUrl":"10.1097/WAD.0000000000000592","url":null,"abstract":"","PeriodicalId":7679,"journal":{"name":"Alzheimer Disease & Associated Disorders","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138443566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-10-01Epub Date: 2023-09-19DOI: 10.1097/WAD.0000000000000582
Michael R Kann, Peter J Zeiger, Sandra J Rizer, Stephanie Cosentino, Martina Azar
Subjective cognitive decline (SCD), a potential early marker for neurodegenerative disease such as Alzheimer's disease, is common among older adults. Although it is often regarded as a personal health concern, most individuals with SCD do not seek help from a health care professional. Help-seeking (HS) is a complex, individualized process with significant life-course implications, and older adults often face several barriers to HS across personal, socioeconomic, and cultural domains. The pandemic exacerbated these barriers by imposing additional limitations on in-person care. In response, virtual assessment became a popular method to conduct remote care. We provide a narrative review of the challenges and triumphs that came with the transition from in-person, pen-paper cognitive assessments to virtual cognitive assessments. In addition, we address the impact virtual assessment had in tackling barriers that previously limited individuals with SCD from formal HS. We argue that virtual cognitive assessment helps alleviate health access barriers to HS (e.g., cost, transportation, and physician availability) and allows individuals with different coping styles to undergo assessment within more convenient environments. We hope the findings presented in this review inform health care practice, public education, and future research targeted towards the use of virtual assessment to facilitate HS in older adults with SCD.
{"title":"Virtual Assessment as a Way to Reduce Help-seeking Barriers in Older Adults With Subjective Cognitive Decline.","authors":"Michael R Kann, Peter J Zeiger, Sandra J Rizer, Stephanie Cosentino, Martina Azar","doi":"10.1097/WAD.0000000000000582","DOIUrl":"10.1097/WAD.0000000000000582","url":null,"abstract":"<p><p>Subjective cognitive decline (SCD), a potential early marker for neurodegenerative disease such as Alzheimer's disease, is common among older adults. Although it is often regarded as a personal health concern, most individuals with SCD do not seek help from a health care professional. Help-seeking (HS) is a complex, individualized process with significant life-course implications, and older adults often face several barriers to HS across personal, socioeconomic, and cultural domains. The pandemic exacerbated these barriers by imposing additional limitations on in-person care. In response, virtual assessment became a popular method to conduct remote care. We provide a narrative review of the challenges and triumphs that came with the transition from in-person, pen-paper cognitive assessments to virtual cognitive assessments. In addition, we address the impact virtual assessment had in tackling barriers that previously limited individuals with SCD from formal HS. We argue that virtual cognitive assessment helps alleviate health access barriers to HS (e.g., cost, transportation, and physician availability) and allows individuals with different coping styles to undergo assessment within more convenient environments. We hope the findings presented in this review inform health care practice, public education, and future research targeted towards the use of virtual assessment to facilitate HS in older adults with SCD.</p>","PeriodicalId":7679,"journal":{"name":"Alzheimer Disease & Associated Disorders","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10719961/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41092322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-10-01Epub Date: 2023-09-20DOI: 10.1097/WAD.0000000000000583
Ashley Kuzmik, Marie Boltz, Barbara Resnick, Brittany F Drazich, James E Galvin
Background: The purpose of this study was to identify factors that are associated with physical activity after hospitalization in persons living with dementia.
Methods: Multiple linear regressions were conducted to test factors associated with objective activity levels (sedentary, low, moderate, and vigorous) among 244 patients living with dementia from a randomized controlled trial.
Results: Within 48 hours of hospital discharge, time in sedentary behavior was associated with increased pain (β=0.164, P =0.015). Time in low activity was associated with less pain (β=-0.130, P =0.049) and higher physical function (β=0.300, P =<0.001). Time in moderate activity was associated with increased physical function (β=0.190, P =0.008) and male gender (β=0.155, P =0.016). No significant associations of potential factors were found with time in vigorous activity.
Conclusions: Our findings suggest that managing or reducing pain, encouraging individual functional level, and gender could influence time spent in physical activity after acute hospitalization in persons living with dementia.
{"title":"Gender, Pain, and Function Associated With Physical Activity After Hospitalization in Persons Living With Dementia.","authors":"Ashley Kuzmik, Marie Boltz, Barbara Resnick, Brittany F Drazich, James E Galvin","doi":"10.1097/WAD.0000000000000583","DOIUrl":"10.1097/WAD.0000000000000583","url":null,"abstract":"<p><strong>Background: </strong>The purpose of this study was to identify factors that are associated with physical activity after hospitalization in persons living with dementia.</p><p><strong>Methods: </strong>Multiple linear regressions were conducted to test factors associated with objective activity levels (sedentary, low, moderate, and vigorous) among 244 patients living with dementia from a randomized controlled trial.</p><p><strong>Results: </strong>Within 48 hours of hospital discharge, time in sedentary behavior was associated with increased pain (β=0.164, P =0.015). Time in low activity was associated with less pain (β=-0.130, P =0.049) and higher physical function (β=0.300, P =<0.001). Time in moderate activity was associated with increased physical function (β=0.190, P =0.008) and male gender (β=0.155, P =0.016). No significant associations of potential factors were found with time in vigorous activity.</p><p><strong>Conclusions: </strong>Our findings suggest that managing or reducing pain, encouraging individual functional level, and gender could influence time spent in physical activity after acute hospitalization in persons living with dementia.</p>","PeriodicalId":7679,"journal":{"name":"Alzheimer Disease & Associated Disorders","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10841226/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41094294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-10-01Epub Date: 2023-09-11DOI: 10.1097/WAD.0000000000000578
Marwan N Sabbagh, Philip Mathew, Alan Blau
Background: A once-weekly donepezil transdermal delivery system (TDS; Adlarity; Corium, LLC) is indicated for the treatment of mild, moderate, and severe dementia of the Alzheimer type. Methods: In this placebo-controlled, randomized, double-blind phase 1 trial, healthy volunteers aged 40 years or older were randomized to receive a placebo and donepezil TDS and were evaluated for the primary endpoints of skin irritation and sensitization potential. Skin irritation was scored. Results: Two hundred fifty-six participants were randomized and received ≥1 dose of any treatment. After the first weekly TDS application, no skin irritation or minimal irritation was evident between donepezil and placebo TDSs. At the third weekly TDS application, for donepezil TDS, the average of the mean combined skin irritation score was 0.55 of a possible maximum of 7, indicating none to minimal skin irritation, and for placebo, the score was 0.19, indicating no skin irritation. Of 198 participants, 4 (2.0%) were considered potentially sensitized to donepezil TDS, and 0 were potentially sensitized to placebo TDS. Conclusion: Once-weekly 5-mg/d donepezil TDS demonstrated minimal skin irritation under conditions of use of 3 consecutive weekly patch applications to the same skin site and minimal sensitization potential.
{"title":"A Randomized Double-blind Study to Assess the Skin Irritation and Sensitization Potential of a Once-weekly Donepezil Transdermal Delivery System in Healthy Volunteers.","authors":"Marwan N Sabbagh, Philip Mathew, Alan Blau","doi":"10.1097/WAD.0000000000000578","DOIUrl":"10.1097/WAD.0000000000000578","url":null,"abstract":"Background: A once-weekly donepezil transdermal delivery system (TDS; Adlarity; Corium, LLC) is indicated for the treatment of mild, moderate, and severe dementia of the Alzheimer type. Methods: In this placebo-controlled, randomized, double-blind phase 1 trial, healthy volunteers aged 40 years or older were randomized to receive a placebo and donepezil TDS and were evaluated for the primary endpoints of skin irritation and sensitization potential. Skin irritation was scored. Results: Two hundred fifty-six participants were randomized and received ≥1 dose of any treatment. After the first weekly TDS application, no skin irritation or minimal irritation was evident between donepezil and placebo TDSs. At the third weekly TDS application, for donepezil TDS, the average of the mean combined skin irritation score was 0.55 of a possible maximum of 7, indicating none to minimal skin irritation, and for placebo, the score was 0.19, indicating no skin irritation. Of 198 participants, 4 (2.0%) were considered potentially sensitized to donepezil TDS, and 0 were potentially sensitized to placebo TDS. Conclusion: Once-weekly 5-mg/d donepezil TDS demonstrated minimal skin irritation under conditions of use of 3 consecutive weekly patch applications to the same skin site and minimal sensitization potential.","PeriodicalId":7679,"journal":{"name":"Alzheimer Disease & Associated Disorders","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10664792/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10554832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-10-01Epub Date: 2023-08-25DOI: 10.1097/WAD.0000000000000577
Tao Wang, Zhiwei Guo, Hongxia Wu, Yi Jiang, Qiwen Mu
Objective: The purpose of this study was to investigate the effects of repetitive transcranial magnetic stimulation (rTMS) on improving memory deficits in mild cognitive impairment (MCI), as well as to provide visualized evidence for neuronal specificity by using resting-state functional magnetic resonance imaging.
Materials and methods: Forty MCI patients were enrolled to receive 10-session and sham-controlled 10Hz-rTMS over the left dorsolateral prefrontal cortex. The resting-state functional magnetic resonance imaging combined with memory scales assessment were performed before and after the intervention. To elucidate the therapeutic mechanism of rTMS, amplitude of low-frequency fluctuations (ALFF) and functional connectivity were calculated. The Pearson correlation was used to measure the relationship between ALFF and memory performance.
Results: Compared with the sham group, ALFF significantly increased in the right insula, right inferior frontal gyrus-opercular part, and decreased in the left middle occipital gyrus, left angular gyrus, and left lingual gyrus after rTMS. The change in Auditory Verbal Learning Test scores were negatively correlated with ALFF decreases in the left lingual gyrus. Functional connectivity significantly increased between the posterior cingulate cortex and right supramarginal gyrus, and decreased between the right frontoinsular cortex and right supramarginal gyrus after intervention.
Conclusion: High-frequency rTMS over the left dorsolateral prefrontal cortex could facilitate improvement on impaired memory in patients with MCI via modulating the neuronal activity and brain network.
{"title":"High-Frequency rTMS Could Improve Impaired Memory in Mild Cognitive Impairment Patients in China: A Randomized Controlled Study.","authors":"Tao Wang, Zhiwei Guo, Hongxia Wu, Yi Jiang, Qiwen Mu","doi":"10.1097/WAD.0000000000000577","DOIUrl":"10.1097/WAD.0000000000000577","url":null,"abstract":"<p><strong>Objective: </strong>The purpose of this study was to investigate the effects of repetitive transcranial magnetic stimulation (rTMS) on improving memory deficits in mild cognitive impairment (MCI), as well as to provide visualized evidence for neuronal specificity by using resting-state functional magnetic resonance imaging.</p><p><strong>Materials and methods: </strong>Forty MCI patients were enrolled to receive 10-session and sham-controlled 10Hz-rTMS over the left dorsolateral prefrontal cortex. The resting-state functional magnetic resonance imaging combined with memory scales assessment were performed before and after the intervention. To elucidate the therapeutic mechanism of rTMS, amplitude of low-frequency fluctuations (ALFF) and functional connectivity were calculated. The Pearson correlation was used to measure the relationship between ALFF and memory performance.</p><p><strong>Results: </strong>Compared with the sham group, ALFF significantly increased in the right insula, right inferior frontal gyrus-opercular part, and decreased in the left middle occipital gyrus, left angular gyrus, and left lingual gyrus after rTMS. The change in Auditory Verbal Learning Test scores were negatively correlated with ALFF decreases in the left lingual gyrus. Functional connectivity significantly increased between the posterior cingulate cortex and right supramarginal gyrus, and decreased between the right frontoinsular cortex and right supramarginal gyrus after intervention.</p><p><strong>Conclusion: </strong>High-frequency rTMS over the left dorsolateral prefrontal cortex could facilitate improvement on impaired memory in patients with MCI via modulating the neuronal activity and brain network.</p>","PeriodicalId":7679,"journal":{"name":"Alzheimer Disease & Associated Disorders","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10060989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-10-01Epub Date: 2023-11-02DOI: 10.1097/WAD.0000000000000588
Tatiana Teresa Belfort Almeida Dos Santos, Marcela Moreira Lima Nogueira, Isabel Barbeito Lacerda, Michelle Brandt, Aline Tavares de Lucena, Rogeria Rangel, Julia Gaigher, Felipe Oliveira, Marcia Cristina Nascimento Dourado
Background: Social cognition (SC) impairments contribute to the dependence of people with Alzheimer disease (AD), influencing their functional disability and the burden on family members and caregivers. Our objective was to longitudinally investigate the relationship between SC and cognitive and clinical variables in persons with AD and their caregivers. We also evaluated the different SC predictors from 3 perspectives: people with AD, caregivers of people with AD, and discrepancy analysis.
Methods: In all, 137 dyads (people with AD and their caregivers) underwent 2 assessments: at baseline (M1) and after 1 year (M2). During follow-up, 58 dyads were excluded, and the study was thus concluded with 79.
Results: Longitudinal analysis of the people with AD showed that while some cognitive functions declined (which is consistent with disease progression), SC impairments showed a more stable pattern. Another interesting result was related to SC predictors. For people with AD, SC was associated with cognition at both time points. For caregivers, besides cognition, other predictors included reduced functional abilities and quality of life in people with AD. These results are consistent with the discrepancy predictors.
Conclusion: The stable pattern in SC functioning over 12 months in AD suggests that this neurocognitive domain may be influenced more by emotional processing than by cognitive impairment. In addition, the SC predictors showed that the investigation of different points of view enables a more global understanding, contributing to better and more targeted treatment for the patient.
{"title":"A Longitudinal Evaluation of the Pattern of Social Cognition Impairment in Brazilians With Alzheimer's Disease.","authors":"Tatiana Teresa Belfort Almeida Dos Santos, Marcela Moreira Lima Nogueira, Isabel Barbeito Lacerda, Michelle Brandt, Aline Tavares de Lucena, Rogeria Rangel, Julia Gaigher, Felipe Oliveira, Marcia Cristina Nascimento Dourado","doi":"10.1097/WAD.0000000000000588","DOIUrl":"10.1097/WAD.0000000000000588","url":null,"abstract":"<p><strong>Background: </strong>Social cognition (SC) impairments contribute to the dependence of people with Alzheimer disease (AD), influencing their functional disability and the burden on family members and caregivers. Our objective was to longitudinally investigate the relationship between SC and cognitive and clinical variables in persons with AD and their caregivers. We also evaluated the different SC predictors from 3 perspectives: people with AD, caregivers of people with AD, and discrepancy analysis.</p><p><strong>Methods: </strong>In all, 137 dyads (people with AD and their caregivers) underwent 2 assessments: at baseline (M1) and after 1 year (M2). During follow-up, 58 dyads were excluded, and the study was thus concluded with 79.</p><p><strong>Results: </strong>Longitudinal analysis of the people with AD showed that while some cognitive functions declined (which is consistent with disease progression), SC impairments showed a more stable pattern. Another interesting result was related to SC predictors. For people with AD, SC was associated with cognition at both time points. For caregivers, besides cognition, other predictors included reduced functional abilities and quality of life in people with AD. These results are consistent with the discrepancy predictors.</p><p><strong>Conclusion: </strong>The stable pattern in SC functioning over 12 months in AD suggests that this neurocognitive domain may be influenced more by emotional processing than by cognitive impairment. In addition, the SC predictors showed that the investigation of different points of view enables a more global understanding, contributing to better and more targeted treatment for the patient.</p>","PeriodicalId":7679,"journal":{"name":"Alzheimer Disease & Associated Disorders","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71419821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-10-01Epub Date: 2023-11-28DOI: 10.1097/WAD.0000000000000590
Youssef Razouqi, Ihssane El Bouchikhi, Hassan El-Abid, Soukayna Baammi, Ayoub Nedbour, Ahmed Omar Touhami Ahami, Achraf El Allali, Laila Bouguenouch
Alzheimer disease (AD) is a major public health concern worldwide. It is a severe neurodegenerative disease that primarily affects the elderly and causes significant brain cell death. According to the most complete scientific research, the APOE gene, which encodes the APOE protein, maybe the key to identifying the likely cause of delayed AD. The development of plaques and tangles, as well as increased amyloid (amyloid-β) levels and deposition, have been linked to APOE4. Pathogenic mutations in this gene can impact how beta-amyloid deposits and how they are cleared from the body. In this study, we report a novel pathogenic mutation, Arg160Leu, in APOE that was identified in a Moroccan patient. The magnetic resonance imaging of this 67-year-old woman revealed hippocampal shrinkage, and the results of her cognition testing revealed that she is suffering from severe AD. The current study may increase awareness of the genetic risk factors for AD caused by APOE4 mutations.
{"title":"Novel APOE Mutation in a Moroccan Subject Suffering from Alzheimer Disease: A Case Study and Exploration of Pathogenic Implication.","authors":"Youssef Razouqi, Ihssane El Bouchikhi, Hassan El-Abid, Soukayna Baammi, Ayoub Nedbour, Ahmed Omar Touhami Ahami, Achraf El Allali, Laila Bouguenouch","doi":"10.1097/WAD.0000000000000590","DOIUrl":"10.1097/WAD.0000000000000590","url":null,"abstract":"<p><p>Alzheimer disease (AD) is a major public health concern worldwide. It is a severe neurodegenerative disease that primarily affects the elderly and causes significant brain cell death. According to the most complete scientific research, the APOE gene, which encodes the APOE protein, maybe the key to identifying the likely cause of delayed AD. The development of plaques and tangles, as well as increased amyloid (amyloid-β) levels and deposition, have been linked to APOE4. Pathogenic mutations in this gene can impact how beta-amyloid deposits and how they are cleared from the body. In this study, we report a novel pathogenic mutation, Arg160Leu, in APOE that was identified in a Moroccan patient. The magnetic resonance imaging of this 67-year-old woman revealed hippocampal shrinkage, and the results of her cognition testing revealed that she is suffering from severe AD. The current study may increase awareness of the genetic risk factors for AD caused by APOE4 mutations.</p>","PeriodicalId":7679,"journal":{"name":"Alzheimer Disease & Associated Disorders","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138443567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-10-01Epub Date: 2023-11-28DOI: 10.1097/WAD.0000000000000589
Konstanze Plaschke, Jürgen Kopitz, Johannes Gebert, Nadine D Wolf, Robert Christian Wolf
Background: Despite substantial progress made in the past decades, the pathogenesis of sporadic Alzheimer disease (sAD) and related biological markers of the disease are still controversially discussed. Cerebrospinal fluid and functional brain imaging markers have been established to support the clinical diagnosis of sAD. Yet, due to the invasiveness of such diagnostics, less burdensome markers have been increasingly investigated in the past years. Among such markers, extracellular vesicles may yield promise in (early) diagnostics and treatment monitoring in sAD.
Materials and methods: In this pilot study, we collected the blood plasma of 18 patients with sAD and compared the proteome of extracted extracellular vesicles with the proteome of 11 age-matched healthy controls. The resulting proteomes were characterized by Gene Ontology terms and between-group statistics.
Results: Ten distinct proteins were found to significantly differ between sAD patients and controls (P<0.05, False Discovery Rate, corrected). These proteins included distinct immunoglobulins, fibronectin, and apolipoproteins.
Conclusions: These findings lend further support for exosomal changes in neurodegenerative disorders, and particularly in sAD. Further proteomic research could decisively advance our knowledge of sAD pathophysiology as much as it could foster the development of clinically meaningful biomarkers.
{"title":"Proteomic Analysis Reveals Potential Exosomal Biomarkers in Patients With Sporadic Alzheimer Disease.","authors":"Konstanze Plaschke, Jürgen Kopitz, Johannes Gebert, Nadine D Wolf, Robert Christian Wolf","doi":"10.1097/WAD.0000000000000589","DOIUrl":"10.1097/WAD.0000000000000589","url":null,"abstract":"<p><strong>Background: </strong>Despite substantial progress made in the past decades, the pathogenesis of sporadic Alzheimer disease (sAD) and related biological markers of the disease are still controversially discussed. Cerebrospinal fluid and functional brain imaging markers have been established to support the clinical diagnosis of sAD. Yet, due to the invasiveness of such diagnostics, less burdensome markers have been increasingly investigated in the past years. Among such markers, extracellular vesicles may yield promise in (early) diagnostics and treatment monitoring in sAD.</p><p><strong>Materials and methods: </strong>In this pilot study, we collected the blood plasma of 18 patients with sAD and compared the proteome of extracted extracellular vesicles with the proteome of 11 age-matched healthy controls. The resulting proteomes were characterized by Gene Ontology terms and between-group statistics.</p><p><strong>Results: </strong>Ten distinct proteins were found to significantly differ between sAD patients and controls (P<0.05, False Discovery Rate, corrected). These proteins included distinct immunoglobulins, fibronectin, and apolipoproteins.</p><p><strong>Conclusions: </strong>These findings lend further support for exosomal changes in neurodegenerative disorders, and particularly in sAD. Further proteomic research could decisively advance our knowledge of sAD pathophysiology as much as it could foster the development of clinically meaningful biomarkers.</p>","PeriodicalId":7679,"journal":{"name":"Alzheimer Disease & Associated Disorders","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138443568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-10-01Epub Date: 2023-11-28DOI: 10.1097/WAD.0000000000000585
Rachel Membreno, Kelsey R Thomas, Amanda T Calcetas, Lauren Edwards, Maria Bordyug, Maya Showell, Morgan Stanfill, Einat K Brenner, Kayla S Walker, Lindsay J Rotblatt, Adam M Brickman, Emily C Edmonds, Katherine J Bangen
Introduction: White matter hyperintensities (WMHs) are magnetic resonance imaging markers of small vessel cerebrovascular disease that are associated with cognitive decline and clinical Alzheimer disease. Previous studies have often focused on global or total WMH; less is known about associations of regional WMHs and cognitive abilities among older adults without dementia.
Methods: A total of 610 older adults with normal cognition (n=302) or mild cognitive impairment (n=308) from the Alzheimer's Disease Neuroimaging Initiative underwent neuropsychological testing and magnetic resonance imaging. Linear regression models examined associations between regional WMH volumes and cognition, adjusting for age, sex, education, apolipoprotein E ε4 allele frequency, and pulse pressure.
Results: Among all participants, greater regional WMH volume in all lobes was associated with poorer performance on memory and speed/executive functioning. Among participants with normal cognition, greater temporal and occipital WMH volumes were associated with poorer memory, whereas no regional WMH volumes were associated with speed/executive function.
Discussion: Results show that greater regional WMH volume relates to poorer cognitive functioning-even among those with normal cognition. Together with results from previous studies, our findings raise the possibility that WMH may be a useful therapeutic target and/or important effect modifier in treatment or prevention dementia trials.
{"title":"Regional White Matter Hyperintensities Relate to Specific Cognitive Abilities in Older Adults Without Dementia.","authors":"Rachel Membreno, Kelsey R Thomas, Amanda T Calcetas, Lauren Edwards, Maria Bordyug, Maya Showell, Morgan Stanfill, Einat K Brenner, Kayla S Walker, Lindsay J Rotblatt, Adam M Brickman, Emily C Edmonds, Katherine J Bangen","doi":"10.1097/WAD.0000000000000585","DOIUrl":"10.1097/WAD.0000000000000585","url":null,"abstract":"<p><strong>Introduction: </strong>White matter hyperintensities (WMHs) are magnetic resonance imaging markers of small vessel cerebrovascular disease that are associated with cognitive decline and clinical Alzheimer disease. Previous studies have often focused on global or total WMH; less is known about associations of regional WMHs and cognitive abilities among older adults without dementia.</p><p><strong>Methods: </strong>A total of 610 older adults with normal cognition (n=302) or mild cognitive impairment (n=308) from the Alzheimer's Disease Neuroimaging Initiative underwent neuropsychological testing and magnetic resonance imaging. Linear regression models examined associations between regional WMH volumes and cognition, adjusting for age, sex, education, apolipoprotein E ε4 allele frequency, and pulse pressure.</p><p><strong>Results: </strong>Among all participants, greater regional WMH volume in all lobes was associated with poorer performance on memory and speed/executive functioning. Among participants with normal cognition, greater temporal and occipital WMH volumes were associated with poorer memory, whereas no regional WMH volumes were associated with speed/executive function.</p><p><strong>Discussion: </strong>Results show that greater regional WMH volume relates to poorer cognitive functioning-even among those with normal cognition. Together with results from previous studies, our findings raise the possibility that WMH may be a useful therapeutic target and/or important effect modifier in treatment or prevention dementia trials.</p>","PeriodicalId":7679,"journal":{"name":"Alzheimer Disease & Associated Disorders","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10664788/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138443569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}