Arterial Stiffening Moderates the Relationship Between Type-2 Diabetes Mellitus and White Matter Hyperintensity Burden in Older Adults With Mild Cognitive Impairment
Background: Cerebrovascular dysfunction has been proposed as a possible mechanism underlying cognitive impairment in the context of type 2 diabetes mellitus (DM). Although magnetic resonance imaging (MRI) evidence of cerebrovascular disease, such as white matter hyperintensities (WMH), is often obse...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-10-01
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| Series: | Frontiers in Aging Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnagi.2021.716638/full |
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| author | Madeleine L. Werhane Kelsey R. Thomas Kelsey R. Thomas Katherine J. Bangen Katherine J. Bangen Alexandra J. Weigand Alexandra J. Weigand Alexandra J. Weigand Emily C. Edmonds Emily C. Edmonds Daniel A. Nation Erin E. Sundermann Mark W. Bondi Mark W. Bondi Lisa Delano-Wood Lisa Delano-Wood |
| author_facet | Madeleine L. Werhane Kelsey R. Thomas Kelsey R. Thomas Katherine J. Bangen Katherine J. Bangen Alexandra J. Weigand Alexandra J. Weigand Alexandra J. Weigand Emily C. Edmonds Emily C. Edmonds Daniel A. Nation Erin E. Sundermann Mark W. Bondi Mark W. Bondi Lisa Delano-Wood Lisa Delano-Wood |
| author_sort | Madeleine L. Werhane |
| collection | DOAJ |
| description | Background: Cerebrovascular dysfunction has been proposed as a possible mechanism underlying cognitive impairment in the context of type 2 diabetes mellitus (DM). Although magnetic resonance imaging (MRI) evidence of cerebrovascular disease, such as white matter hyperintensities (WMH), is often observed in DM, the vascular dynamics underlying this pathology remain unclear. Thus, we assessed the independent and combined effects of DM status and different vascular hemodynamic measures (i.e., systolic, diastolic, and mean arterial blood pressure and pulse pressure index [PPi]) on WMH burden in cognitively unimpaired (CU) older adults and those with mild cognitive impairment (MCI).Methods: 559 older adults (mean age: 72.4 years) from the Alzheimer’s Disease Neuroimaging Initiative were categorized into those with diabetes (DM+; CU = 43, MCI = 34) or without diabetes (DM-; CU = 279; MCI = 203). Participants underwent BP assessment, from which all vascular hemodynamic measures were derived. T2-FLAIR MRI was used to quantify WMH burden. Hierarchical linear regression, adjusting for age, sex, BMI, intracranial volume, CSF amyloid, and APOE ε4 status, examined the independent and interactive effects of DM status and each vascular hemodynamic measure on total WMH burden.Results: The presence of DM (p = 0.046), but not PPi values (p = 0.299), was independently associated with greater WMH burden overall after adjusting for covariates. Analyses stratified by cognitive status revealed a significant DM status x PPi interaction within the MCI group (p = 0.001) such that higher PPi values predicted greater WMH burden in the DM + but not DM- group. No significant interactions were observed in the CU group (all ps > 0.05).Discussion: Results indicate that higher PPi values are positively associated with WMH burden in diabetic older adults with MCI, but not their non-diabetic or CU counterparts. Our findings suggest that arterial stiffening and reduced vascular compliance may have a role in development of cerebrovascular pathology within the context of DM in individuals at risk for future cognitive decline. Given the specificity of these findings to MCI, future exploration of the sensitivity of earlier brain markers of vascular insufficiency (i.e., prior to macrostructural white matter changes) to the effects of DM and arterial stiffness/reduced vascular compliance in CU individuals is warranted. |
| first_indexed | 2024-12-20T17:53:03Z |
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| id | doaj.art-4424ed3fc2394a3ba7f13093a5242c58 |
| institution | Directory Open Access Journal |
| issn | 1663-4365 |
| language | English |
| last_indexed | 2024-12-20T17:53:03Z |
| publishDate | 2021-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Aging Neuroscience |
| spelling | doaj.art-4424ed3fc2394a3ba7f13093a5242c582022-12-21T19:30:48ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652021-10-011310.3389/fnagi.2021.716638716638Arterial Stiffening Moderates the Relationship Between Type-2 Diabetes Mellitus and White Matter Hyperintensity Burden in Older Adults With Mild Cognitive ImpairmentMadeleine L. Werhane0Kelsey R. Thomas1Kelsey R. Thomas2Katherine J. Bangen3Katherine J. Bangen4Alexandra J. Weigand5Alexandra J. Weigand6Alexandra J. Weigand7Emily C. Edmonds8Emily C. Edmonds9Daniel A. Nation10Erin E. Sundermann11Mark W. Bondi12Mark W. Bondi13Lisa Delano-Wood14Lisa Delano-Wood15Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, United StatesVA San Diego Healthcare System, San Diego, CA, United StatesDepartment of Psychiatry, University of California, San Diego, La Jolla, CA, United StatesVA San Diego Healthcare System, San Diego, CA, United StatesDepartment of Psychiatry, University of California, San Diego, La Jolla, CA, United StatesVA San Diego Healthcare System, San Diego, CA, United StatesDepartment of Psychiatry, University of California, San Diego, La Jolla, CA, United StatesSDSU/UC San Diego Joint Doctoral Program in Clinical Psychology, San Diego State University/University of California, San Diego, San Diego, CA, United StatesVA San Diego Healthcare System, San Diego, CA, United StatesDepartment of Psychiatry, University of California, San Diego, La Jolla, CA, United StatesDepartment of Psychological Sciences, University of California, Irvine, Irvine, CA, United StatesDepartment of Psychiatry, University of California, San Diego, La Jolla, CA, United StatesVA San Diego Healthcare System, San Diego, CA, United StatesDepartment of Psychiatry, University of California, San Diego, La Jolla, CA, United StatesVA San Diego Healthcare System, San Diego, CA, United StatesDepartment of Psychiatry, University of California, San Diego, La Jolla, CA, United StatesBackground: Cerebrovascular dysfunction has been proposed as a possible mechanism underlying cognitive impairment in the context of type 2 diabetes mellitus (DM). Although magnetic resonance imaging (MRI) evidence of cerebrovascular disease, such as white matter hyperintensities (WMH), is often observed in DM, the vascular dynamics underlying this pathology remain unclear. Thus, we assessed the independent and combined effects of DM status and different vascular hemodynamic measures (i.e., systolic, diastolic, and mean arterial blood pressure and pulse pressure index [PPi]) on WMH burden in cognitively unimpaired (CU) older adults and those with mild cognitive impairment (MCI).Methods: 559 older adults (mean age: 72.4 years) from the Alzheimer’s Disease Neuroimaging Initiative were categorized into those with diabetes (DM+; CU = 43, MCI = 34) or without diabetes (DM-; CU = 279; MCI = 203). Participants underwent BP assessment, from which all vascular hemodynamic measures were derived. T2-FLAIR MRI was used to quantify WMH burden. Hierarchical linear regression, adjusting for age, sex, BMI, intracranial volume, CSF amyloid, and APOE ε4 status, examined the independent and interactive effects of DM status and each vascular hemodynamic measure on total WMH burden.Results: The presence of DM (p = 0.046), but not PPi values (p = 0.299), was independently associated with greater WMH burden overall after adjusting for covariates. Analyses stratified by cognitive status revealed a significant DM status x PPi interaction within the MCI group (p = 0.001) such that higher PPi values predicted greater WMH burden in the DM + but not DM- group. No significant interactions were observed in the CU group (all ps > 0.05).Discussion: Results indicate that higher PPi values are positively associated with WMH burden in diabetic older adults with MCI, but not their non-diabetic or CU counterparts. Our findings suggest that arterial stiffening and reduced vascular compliance may have a role in development of cerebrovascular pathology within the context of DM in individuals at risk for future cognitive decline. Given the specificity of these findings to MCI, future exploration of the sensitivity of earlier brain markers of vascular insufficiency (i.e., prior to macrostructural white matter changes) to the effects of DM and arterial stiffness/reduced vascular compliance in CU individuals is warranted.https://www.frontiersin.org/articles/10.3389/fnagi.2021.716638/fullmild cognitive impairmentwhite matter hyperintensity volumeblood pressurearterial stiffnessdiabetes |
| spellingShingle | Madeleine L. Werhane Kelsey R. Thomas Kelsey R. Thomas Katherine J. Bangen Katherine J. Bangen Alexandra J. Weigand Alexandra J. Weigand Alexandra J. Weigand Emily C. Edmonds Emily C. Edmonds Daniel A. Nation Erin E. Sundermann Mark W. Bondi Mark W. Bondi Lisa Delano-Wood Lisa Delano-Wood Arterial Stiffening Moderates the Relationship Between Type-2 Diabetes Mellitus and White Matter Hyperintensity Burden in Older Adults With Mild Cognitive Impairment Frontiers in Aging Neuroscience mild cognitive impairment white matter hyperintensity volume blood pressure arterial stiffness diabetes |
| title | Arterial Stiffening Moderates the Relationship Between Type-2 Diabetes Mellitus and White Matter Hyperintensity Burden in Older Adults With Mild Cognitive Impairment |
| title_full | Arterial Stiffening Moderates the Relationship Between Type-2 Diabetes Mellitus and White Matter Hyperintensity Burden in Older Adults With Mild Cognitive Impairment |
| title_fullStr | Arterial Stiffening Moderates the Relationship Between Type-2 Diabetes Mellitus and White Matter Hyperintensity Burden in Older Adults With Mild Cognitive Impairment |
| title_full_unstemmed | Arterial Stiffening Moderates the Relationship Between Type-2 Diabetes Mellitus and White Matter Hyperintensity Burden in Older Adults With Mild Cognitive Impairment |
| title_short | Arterial Stiffening Moderates the Relationship Between Type-2 Diabetes Mellitus and White Matter Hyperintensity Burden in Older Adults With Mild Cognitive Impairment |
| title_sort | arterial stiffening moderates the relationship between type 2 diabetes mellitus and white matter hyperintensity burden in older adults with mild cognitive impairment |
| topic | mild cognitive impairment white matter hyperintensity volume blood pressure arterial stiffness diabetes |
| url | https://www.frontiersin.org/articles/10.3389/fnagi.2021.716638/full |
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