{"title":"内侧颞叶和新皮层的Tau病理学：对认知未受损老年人认知未受损的影响。","authors":"İdris Demirsoy","doi":"10.4274/balkanmedj.galenos.2025.2025-2-93","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The accumulation of proteins such as amyloid-beta and tau, which disrupt normal cellular processes, characterizes Alzheimer's disease (AD). Cognitive decline is strongly linked to tau pathology, which initially manifests in the medial temporal lobe (MTL).</p><p><strong>Aims: </strong>To investigated the association between cognitive performance and regional tau accumulation, as measured by positron emission tomography (PET) imaging, in cognitively normal older adults. Understanding this relationship is critical for early intervention before noticeable cognitive decline emerges.</p><p><strong>Study design: </strong>Retrospective study.</p><p><strong>Methods: </strong>Tau PET scans were conducted on 440 participants enrolled in the anti-amyloid treatment in asymptomatic Alzheimer's (A4) study. The participants, aged 65-85, were cognitively unimpaired and had complete demographic and genetic profiles. Tau levels in the MTL and temporal neocortex (NEO) was quantified using composite metrics. Cognitive function was evaluated using the preclinical Alzheimer's cognitive composite (PACC) and its individual components. Multiple linear regression models were applied to determine the associations between tau burden and cognitive outcomes, including interaction terms to evaluate the moderating roles of sex and apolipoprotein E (APOE)-ε4 genotype.</p><p><strong>Results: </strong>The average participant age was 71.8 years (standard deviation = 4.84), with females comprising 58% of the sample. Greater tau accumulation in both tauMTL and tauNEO regions was significantly associated with lower cognitive scores. Specifically, reduced PACC scores (<i>p</i> < 0.001) corresponded with higher tau levels in both regions, primarily influenced by declines in Delayed Logical Memory and Free and Cued Selective Reminding test scores. Additionally, tauNEO levels were modestly linked to Mini-Mental State Examination scores. The effects of sex and APOE-ε4 status were minimal.</p><p><strong>Conclusion: </strong>Elevated tau deposition in the MTL and NEO is associated with diminished cognitive function, particularly in memory and processing speed domains. Notably, tau accumulation in the MTL showed a strong association with poorer outcomes on memory-related cognitive measures. The limited influence of sex and APOE-ε4 genotype highlights tau pathology as a key contributor to early cognitive decline in preclinical AD.</p>","PeriodicalId":8690,"journal":{"name":"Balkan Medical Journal","volume":"42 4","pages":"329-338"},"PeriodicalIF":1.9000,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12240214/pdf/","citationCount":"0","resultStr":"{\"title\":\"Tau Pathology in the Medial Temporal Lobe and Neocortex: Implications for Cognitive Unimpaired in Cognitively Unimpaired Older Adults.\",\"authors\":\"İdris Demirsoy\",\"doi\":\"10.4274/balkanmedj.galenos.2025.2025-2-93\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>The accumulation of proteins such as amyloid-beta and tau, which disrupt normal cellular processes, characterizes Alzheimer's disease (AD). Cognitive decline is strongly linked to tau pathology, which initially manifests in the medial temporal lobe (MTL).</p><p><strong>Aims: </strong>To investigated the association between cognitive performance and regional tau accumulation, as measured by positron emission tomography (PET) imaging, in cognitively normal older adults. Understanding this relationship is critical for early intervention before noticeable cognitive decline emerges.</p><p><strong>Study design: </strong>Retrospective study.</p><p><strong>Methods: </strong>Tau PET scans were conducted on 440 participants enrolled in the anti-amyloid treatment in asymptomatic Alzheimer's (A4) study. The participants, aged 65-85, were cognitively unimpaired and had complete demographic and genetic profiles. Tau levels in the MTL and temporal neocortex (NEO) was quantified using composite metrics. Cognitive function was evaluated using the preclinical Alzheimer's cognitive composite (PACC) and its individual components. Multiple linear regression models were applied to determine the associations between tau burden and cognitive outcomes, including interaction terms to evaluate the moderating roles of sex and apolipoprotein E (APOE)-ε4 genotype.</p><p><strong>Results: </strong>The average participant age was 71.8 years (standard deviation = 4.84), with females comprising 58% of the sample. Greater tau accumulation in both tauMTL and tauNEO regions was significantly associated with lower cognitive scores. Specifically, reduced PACC scores (<i>p</i> < 0.001) corresponded with higher tau levels in both regions, primarily influenced by declines in Delayed Logical Memory and Free and Cued Selective Reminding test scores. Additionally, tauNEO levels were modestly linked to Mini-Mental State Examination scores. The effects of sex and APOE-ε4 status were minimal.</p><p><strong>Conclusion: </strong>Elevated tau deposition in the MTL and NEO is associated with diminished cognitive function, particularly in memory and processing speed domains. Notably, tau accumulation in the MTL showed a strong association with poorer outcomes on memory-related cognitive measures. The limited influence of sex and APOE-ε4 genotype highlights tau pathology as a key contributor to early cognitive decline in preclinical AD.</p>\",\"PeriodicalId\":8690,\"journal\":{\"name\":\"Balkan Medical Journal\",\"volume\":\"42 4\",\"pages\":\"329-338\"},\"PeriodicalIF\":1.9000,\"publicationDate\":\"2025-07-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12240214/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Balkan Medical Journal\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.4274/balkanmedj.galenos.2025.2025-2-93\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"MEDICINE, GENERAL & INTERNAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Balkan Medical Journal","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.4274/balkanmedj.galenos.2025.2025-2-93","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MEDICINE, GENERAL & INTERNAL","Score":null,"Total":0}
Tau Pathology in the Medial Temporal Lobe and Neocortex: Implications for Cognitive Unimpaired in Cognitively Unimpaired Older Adults.
Background: The accumulation of proteins such as amyloid-beta and tau, which disrupt normal cellular processes, characterizes Alzheimer's disease (AD). Cognitive decline is strongly linked to tau pathology, which initially manifests in the medial temporal lobe (MTL).
Aims: To investigated the association between cognitive performance and regional tau accumulation, as measured by positron emission tomography (PET) imaging, in cognitively normal older adults. Understanding this relationship is critical for early intervention before noticeable cognitive decline emerges.
Study design: Retrospective study.
Methods: Tau PET scans were conducted on 440 participants enrolled in the anti-amyloid treatment in asymptomatic Alzheimer's (A4) study. The participants, aged 65-85, were cognitively unimpaired and had complete demographic and genetic profiles. Tau levels in the MTL and temporal neocortex (NEO) was quantified using composite metrics. Cognitive function was evaluated using the preclinical Alzheimer's cognitive composite (PACC) and its individual components. Multiple linear regression models were applied to determine the associations between tau burden and cognitive outcomes, including interaction terms to evaluate the moderating roles of sex and apolipoprotein E (APOE)-ε4 genotype.
Results: The average participant age was 71.8 years (standard deviation = 4.84), with females comprising 58% of the sample. Greater tau accumulation in both tauMTL and tauNEO regions was significantly associated with lower cognitive scores. Specifically, reduced PACC scores (p < 0.001) corresponded with higher tau levels in both regions, primarily influenced by declines in Delayed Logical Memory and Free and Cued Selective Reminding test scores. Additionally, tauNEO levels were modestly linked to Mini-Mental State Examination scores. The effects of sex and APOE-ε4 status were minimal.
Conclusion: Elevated tau deposition in the MTL and NEO is associated with diminished cognitive function, particularly in memory and processing speed domains. Notably, tau accumulation in the MTL showed a strong association with poorer outcomes on memory-related cognitive measures. The limited influence of sex and APOE-ε4 genotype highlights tau pathology as a key contributor to early cognitive decline in preclinical AD.
期刊介绍：
The Balkan Medical Journal (Balkan Med J) is a peer-reviewed open-access international journal that publishes interesting clinical and experimental research conducted in all fields of medicine, interesting case reports and clinical images, invited reviews, editorials, letters, comments and letters to the Editor including reports on publication and research ethics. The journal is the official scientific publication of the Trakya University Faculty of Medicine, Edirne, Turkey and is printed six times a year, in January, March, May, July, September and November. The language of the journal is English.
The journal is based on independent and unbiased double-blinded peer-reviewed principles. Only unpublished papers that are not under review for publication elsewhere can be submitted. Balkan Medical Journal does not accept multiple submission and duplicate submission even though the previous one was published in a different language. The authors are responsible for the scientific content of the material to be published. The Balkan Medical Journal reserves the right to request any research materials on which the paper is based.
The Balkan Medical Journal encourages and enables academicians, researchers, specialists and primary care physicians of Balkan countries to publish their valuable research in all branches of medicine. The primary aim of the journal is to publish original articles with high scientific and ethical quality and serve as a good example of medical publications in the Balkans as well as in the World.
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