Longitudinal Intraindividual Cognitive Variability Is Associated With Reduction in Regional Cerebral Blood Flow Among Alzheimer’s Disease Biomarker-Positive Older Adults
Intraindividual variability (IIV) across neuropsychological measures within a single testing session is a promising marker predictive of cognitive decline and development of Alzheimer’s disease (AD). We have previously shown that greater IIV is cross-sectionally associated with reduced cerebral bloo...
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| Format: | Article |
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Frontiers Media S.A.
2022-07-01
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| Series: | Frontiers in Aging Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnagi.2022.859873/full |
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| author | Sophia L. Holmqvist Kelsey R. Thomas Kelsey R. Thomas Einat K. Brenner Emily C. Edmonds Emily C. Edmonds Amanda Calcetas Lauren Edwards Maria Bordyug Katherine J. Bangen Katherine J. Bangen |
| author_facet | Sophia L. Holmqvist Kelsey R. Thomas Kelsey R. Thomas Einat K. Brenner Emily C. Edmonds Emily C. Edmonds Amanda Calcetas Lauren Edwards Maria Bordyug Katherine J. Bangen Katherine J. Bangen |
| author_sort | Sophia L. Holmqvist |
| collection | DOAJ |
| description | Intraindividual variability (IIV) across neuropsychological measures within a single testing session is a promising marker predictive of cognitive decline and development of Alzheimer’s disease (AD). We have previously shown that greater IIV is cross-sectionally associated with reduced cerebral blood flow (CBF), but not with cortical thickness or brain volume, in older adults without dementia who were amyloid beta (Aβ) positive. However, there is little known about the association between change in IIV and CBF over time. Therefore, we examined 12-month longitudinal change in IIV and interactions of IIV and AD biomarker status on changes in regional CBF. Fifty-three non-demented Alzheimer’s Disease Neuroimaging Initiative (ADNI) participants underwent lumbar puncture to obtain cerebrospinal fluid (CSF) at baseline and neuropsychological testing and magnetic resonance imaging (MRI) exams at baseline and 12-month follow-up evaluation. IIV was calculated as the intraindividual standard deviation across 6 demographically-corrected neuropsychological measures. Pulsed arterial spin labeling (ASL) MRI was acquired to quantify CBF and FreeSurfer-derived a priori CBF regions of interest (ROIs) were examined. AD biomarker positivity was determined using a published CSF p-tau/Aβ ratio cut-score. Change scores were calculated for IIV, CBF, and mean neuropsychological performance from baseline to 12 months. Hierarchical linear regression models showed that after adjusting for age and gender, there was a significant interaction between IIV change and biomarker-positivity (p-tau/Aβ+) for change in entorhinal and hippocampal CBF but not for the other ROIs. Specifically, increases in IIV were associated with reductions in entorhinal and hippocampal CBF among individuals who were biomarker-positive (n = 21). In contrast, there were no significant associations between change in IIV and CBF among those who were biomarker-negative (n = 32). Findings remained similar when analyses were performed adjusting for change in mean level of neuropsychological performance. Changes in IIV may be sensitive to changes in regional hypoperfusion in AD-vulnerable regions among AD biomarker-positive individuals, above and beyond demographics and mean neuropsychological performance. These findings provide further evidence supporting IIV as a potential marker of cerebrovascular brain changes in individuals at risk for dementia. |
| first_indexed | 2024-04-13T14:41:48Z |
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| id | doaj.art-cb7a4f4675b74bb8bd6cb76ea23919d2 |
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| issn | 1663-4365 |
| language | English |
| last_indexed | 2024-04-13T14:41:48Z |
| publishDate | 2022-07-01 |
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| series | Frontiers in Aging Neuroscience |
| spelling | doaj.art-cb7a4f4675b74bb8bd6cb76ea23919d22022-12-22T02:42:53ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652022-07-011410.3389/fnagi.2022.859873859873Longitudinal Intraindividual Cognitive Variability Is Associated With Reduction in Regional Cerebral Blood Flow Among Alzheimer’s Disease Biomarker-Positive Older AdultsSophia L. Holmqvist0Kelsey R. Thomas1Kelsey R. Thomas2Einat K. Brenner3Emily C. Edmonds4Emily C. Edmonds5Amanda Calcetas6Lauren Edwards7Maria Bordyug8Katherine J. Bangen9Katherine J. Bangen10Research Service, VA San Diego Healthcare System, San Diego, CA, United StatesResearch Service, VA San Diego Healthcare System, San Diego, CA, United StatesDepartment of Psychiatry, University of California, San Diego, La Jolla, CA, United StatesDepartment of Psychiatry, University of California, San Diego, La Jolla, CA, United StatesResearch Service, VA San Diego Healthcare System, San Diego, CA, United StatesDepartment of Psychiatry, University of California, San Diego, La Jolla, CA, United StatesDepartment of Psychiatry, University of California, San Diego, La Jolla, CA, United StatesSan Diego State University/University of California San Diego Joint Doctoral Program in Clinical Psychology, San Diego, CA, United StatesDepartment of Psychiatry, University of California, San Diego, La Jolla, CA, United StatesResearch Service, VA San Diego Healthcare System, San Diego, CA, United StatesDepartment of Psychiatry, University of California, San Diego, La Jolla, CA, United StatesIntraindividual variability (IIV) across neuropsychological measures within a single testing session is a promising marker predictive of cognitive decline and development of Alzheimer’s disease (AD). We have previously shown that greater IIV is cross-sectionally associated with reduced cerebral blood flow (CBF), but not with cortical thickness or brain volume, in older adults without dementia who were amyloid beta (Aβ) positive. However, there is little known about the association between change in IIV and CBF over time. Therefore, we examined 12-month longitudinal change in IIV and interactions of IIV and AD biomarker status on changes in regional CBF. Fifty-three non-demented Alzheimer’s Disease Neuroimaging Initiative (ADNI) participants underwent lumbar puncture to obtain cerebrospinal fluid (CSF) at baseline and neuropsychological testing and magnetic resonance imaging (MRI) exams at baseline and 12-month follow-up evaluation. IIV was calculated as the intraindividual standard deviation across 6 demographically-corrected neuropsychological measures. Pulsed arterial spin labeling (ASL) MRI was acquired to quantify CBF and FreeSurfer-derived a priori CBF regions of interest (ROIs) were examined. AD biomarker positivity was determined using a published CSF p-tau/Aβ ratio cut-score. Change scores were calculated for IIV, CBF, and mean neuropsychological performance from baseline to 12 months. Hierarchical linear regression models showed that after adjusting for age and gender, there was a significant interaction between IIV change and biomarker-positivity (p-tau/Aβ+) for change in entorhinal and hippocampal CBF but not for the other ROIs. Specifically, increases in IIV were associated with reductions in entorhinal and hippocampal CBF among individuals who were biomarker-positive (n = 21). In contrast, there were no significant associations between change in IIV and CBF among those who were biomarker-negative (n = 32). Findings remained similar when analyses were performed adjusting for change in mean level of neuropsychological performance. Changes in IIV may be sensitive to changes in regional hypoperfusion in AD-vulnerable regions among AD biomarker-positive individuals, above and beyond demographics and mean neuropsychological performance. These findings provide further evidence supporting IIV as a potential marker of cerebrovascular brain changes in individuals at risk for dementia.https://www.frontiersin.org/articles/10.3389/fnagi.2022.859873/fullneuropsychologyintra-individual variabilityagingcerebral blood flow (CBF)magnetic resonance imaging (MRI)Alzheimer’s disease |
| spellingShingle | Sophia L. Holmqvist Kelsey R. Thomas Kelsey R. Thomas Einat K. Brenner Emily C. Edmonds Emily C. Edmonds Amanda Calcetas Lauren Edwards Maria Bordyug Katherine J. Bangen Katherine J. Bangen Longitudinal Intraindividual Cognitive Variability Is Associated With Reduction in Regional Cerebral Blood Flow Among Alzheimer’s Disease Biomarker-Positive Older Adults Frontiers in Aging Neuroscience neuropsychology intra-individual variability aging cerebral blood flow (CBF) magnetic resonance imaging (MRI) Alzheimer’s disease |
| title | Longitudinal Intraindividual Cognitive Variability Is Associated With Reduction in Regional Cerebral Blood Flow Among Alzheimer’s Disease Biomarker-Positive Older Adults |
| title_full | Longitudinal Intraindividual Cognitive Variability Is Associated With Reduction in Regional Cerebral Blood Flow Among Alzheimer’s Disease Biomarker-Positive Older Adults |
| title_fullStr | Longitudinal Intraindividual Cognitive Variability Is Associated With Reduction in Regional Cerebral Blood Flow Among Alzheimer’s Disease Biomarker-Positive Older Adults |
| title_full_unstemmed | Longitudinal Intraindividual Cognitive Variability Is Associated With Reduction in Regional Cerebral Blood Flow Among Alzheimer’s Disease Biomarker-Positive Older Adults |
| title_short | Longitudinal Intraindividual Cognitive Variability Is Associated With Reduction in Regional Cerebral Blood Flow Among Alzheimer’s Disease Biomarker-Positive Older Adults |
| title_sort | longitudinal intraindividual cognitive variability is associated with reduction in regional cerebral blood flow among alzheimer s disease biomarker positive older adults |
| topic | neuropsychology intra-individual variability aging cerebral blood flow (CBF) magnetic resonance imaging (MRI) Alzheimer’s disease |
| url | https://www.frontiersin.org/articles/10.3389/fnagi.2022.859873/full |
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