Does synaptic hypometabolism or synaptic dysfunction, originate cognitive loss? Analysis of the evidence
Abstract Elderly persons with currently normal cognition who have cerebral hypometabolism as shown by low uptake of 18fluorine‐fluorodeoxyglucose (18F‐FDG), are at risk of future loss of cognition and, thus, of future Alzheimer's dementia (AD). Reduction of either 18F‐FDG or cognition is assume...
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| Format: | Article |
| Language: | English |
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Wiley
2021-01-01
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| Series: | Alzheimer’s & Dementia: Translational Research & Clinical Interventions |
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| Online Access: | https://doi.org/10.1002/trc2.12177 |
| _version_ | 1828199368479473664 |
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| author | Jeffrey Fessel |
| author_facet | Jeffrey Fessel |
| author_sort | Jeffrey Fessel |
| collection | DOAJ |
| description | Abstract Elderly persons with currently normal cognition who have cerebral hypometabolism as shown by low uptake of 18fluorine‐fluorodeoxyglucose (18F‐FDG), are at risk of future loss of cognition and, thus, of future Alzheimer's dementia (AD). Reduction of either 18F‐FDG or cognition is assumed to reflect synaptic dysfunction, since synapses account for the majority of glucose use by the brain and cognition depends upon accurate synaptic function. The chronology of the connection between reduced cerebral synaptic function and hypometabolism is, therefore, a critical question, because if synaptic dysfunction came first, then correcting the hypometabolism would likely not benefit synaptic function; but if hypometabolism came first, then correcting the hypometabolism probably would benefit synaptic function. That correction might prevent initiation of the cognitive loss that eventuates in AD and, thereby, would benefit the vast numbers of persons in their eighth to tenth decades of life who are at risk for AD. Among the many citations reviewed in this presentation, seven show hypometabolism that precedes synaptic dysfunction, and two show the reverse. Thus the preponderance of evidence, 78%, suggests that the initiating event is synaptic hypometabolism and that it is 3.5‐fold less likely that synaptic dysfunction is the initiator. In addition, it is inherently unlikely that synaptic dysfunction causes hypometabolism. This conclusion could be tested by a clinical trial whose primary objective would be to assess the benefit to cognition of improving synaptic metabolism in patients who are at risk for cognitive loss. |
| first_indexed | 2024-04-12T10:55:27Z |
| format | Article |
| id | doaj.art-3546e55184ff4101a6dd47bf12f0d3ca |
| institution | Directory Open Access Journal |
| issn | 2352-8737 |
| language | English |
| last_indexed | 2024-04-12T10:55:27Z |
| publishDate | 2021-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Alzheimer’s & Dementia: Translational Research & Clinical Interventions |
| spelling | doaj.art-3546e55184ff4101a6dd47bf12f0d3ca2022-12-22T03:36:07ZengWileyAlzheimer’s & Dementia: Translational Research & Clinical Interventions2352-87372021-01-0171n/an/a10.1002/trc2.12177Does synaptic hypometabolism or synaptic dysfunction, originate cognitive loss? Analysis of the evidenceJeffrey Fessel0Department of Medicine University of California San Francisco California USAAbstract Elderly persons with currently normal cognition who have cerebral hypometabolism as shown by low uptake of 18fluorine‐fluorodeoxyglucose (18F‐FDG), are at risk of future loss of cognition and, thus, of future Alzheimer's dementia (AD). Reduction of either 18F‐FDG or cognition is assumed to reflect synaptic dysfunction, since synapses account for the majority of glucose use by the brain and cognition depends upon accurate synaptic function. The chronology of the connection between reduced cerebral synaptic function and hypometabolism is, therefore, a critical question, because if synaptic dysfunction came first, then correcting the hypometabolism would likely not benefit synaptic function; but if hypometabolism came first, then correcting the hypometabolism probably would benefit synaptic function. That correction might prevent initiation of the cognitive loss that eventuates in AD and, thereby, would benefit the vast numbers of persons in their eighth to tenth decades of life who are at risk for AD. Among the many citations reviewed in this presentation, seven show hypometabolism that precedes synaptic dysfunction, and two show the reverse. Thus the preponderance of evidence, 78%, suggests that the initiating event is synaptic hypometabolism and that it is 3.5‐fold less likely that synaptic dysfunction is the initiator. In addition, it is inherently unlikely that synaptic dysfunction causes hypometabolism. This conclusion could be tested by a clinical trial whose primary objective would be to assess the benefit to cognition of improving synaptic metabolism in patients who are at risk for cognitive loss.https://doi.org/10.1002/trc2.12177cognitionelderly persons18F‐FDGhypometabolisminitiating causeprevention |
| spellingShingle | Jeffrey Fessel Does synaptic hypometabolism or synaptic dysfunction, originate cognitive loss? Analysis of the evidence Alzheimer’s & Dementia: Translational Research & Clinical Interventions cognition elderly persons 18F‐FDG hypometabolism initiating cause prevention |
| title | Does synaptic hypometabolism or synaptic dysfunction, originate cognitive loss? Analysis of the evidence |
| title_full | Does synaptic hypometabolism or synaptic dysfunction, originate cognitive loss? Analysis of the evidence |
| title_fullStr | Does synaptic hypometabolism or synaptic dysfunction, originate cognitive loss? Analysis of the evidence |
| title_full_unstemmed | Does synaptic hypometabolism or synaptic dysfunction, originate cognitive loss? Analysis of the evidence |
| title_short | Does synaptic hypometabolism or synaptic dysfunction, originate cognitive loss? Analysis of the evidence |
| title_sort | does synaptic hypometabolism or synaptic dysfunction originate cognitive loss analysis of the evidence |
| topic | cognition elderly persons 18F‐FDG hypometabolism initiating cause prevention |
| url | https://doi.org/10.1002/trc2.12177 |
| work_keys_str_mv | AT jeffreyfessel doessynaptichypometabolismorsynapticdysfunctionoriginatecognitivelossanalysisoftheevidence |