Cerebrospinal fluid dynamics disorders: Relationship to Alzheimer biomarkers and cognition

Jonathan Graff-Radford, Jeffrey L. Gunter, David T. Jones, Scott A. Przybelski, Christopher G. Schwarz, John Huston, Val Lowe, Benjamin D. Elder, Mary M. Machulda, Nathaniel B. Gunter, Ronald C. Petersen, Kejal Kantarci, Prashanthi Vemuri, Michelle M. Mielke, David S. Knopman, Neill R. Graff-Radford, Clifford R. Jack

Research output: Contribution to journalArticle

Abstract

OBJECTIVE: To determine the frequency of high-convexity tight sulci (HCTS) in a population-based sample and whether the presence of HCTS and related features influenced participants' cognitive status and classification within the new Alzheimer-biomarker framework. METHODS: We analyzed 684 participants ≥50 years of age who were enrolled in the prospective population-based Mayo Clinic Study of Aging and underwent structural MRI, amyloid PET imaging, and tau PET imaging. A fully automated machine-learning algorithm that had been developed previously in house was used to detect neuroimaging features of HCTS. On the basis of PET and MRI measures, participants were classified as having normal (A-) or abnormal (A+) amyloid, normal (T-) or abnormal (T+) tau, and normal (N-) or abnormal (N+) neurodegeneration. The neuropsychological battery assessed domain-specific and global cognitive scores. Gait speed also was assessed. Analyses were adjusted for age and sex. RESULTS: Of 684 participants, 45 (6.6%) were classified with HCTS according to the automated algorithm. Patients with HCTS were older than patients without HCTS (mean [SD] 78.0 [8.3] vs 71.9 [10.8] years; p < 0.001). More were cognitively impaired after age and sex adjustment (27% vs 9%; p = 0.005). Amyloid PET status was similar with and without HCTS, but tau PET standard uptake value ratio (SUVR) was lower for those with HCTS after age and sex adjustment (p < 0.001). Despite a lower tau SUVR, patients with HCTS had lower Alzheimer disease (AD) signature cortical thickness. With the amyloid-tau-neurodegeneration framework, HCTS was overrepresented in the T-(N)+ group, regardless of amyloid status. CONCLUSION: The HCTS pattern represents a definable subgroup of non-AD pathophysiology (i.e., T-[N]+) that is associated with cognitive impairment. HCTS may confound clinical and biomarker interpretation in AD clinical trials.

Original languageEnglish (US)
Pages (from-to)e2237-e2246
JournalNeurology
Volume93
Issue number24
DOIs
StatePublished - Dec 10 2019

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Hydrodynamics
Amyloid
Cognition
Cerebrospinal Fluid
Biomarkers
Social Adjustment
Alzheimer Disease
Neuroimaging
Population
Clinical Trials

ASJC Scopus subject areas

  • Clinical Neurology

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Graff-Radford, J., Gunter, J. L., Jones, D. T., Przybelski, S. A., Schwarz, C. G., Huston, J., ... Jack, C. R. (2019). Cerebrospinal fluid dynamics disorders: Relationship to Alzheimer biomarkers and cognition. Neurology, 93(24), e2237-e2246. https://doi.org/10.1212/WNL.0000000000008616

Cerebrospinal fluid dynamics disorders : Relationship to Alzheimer biomarkers and cognition. / Graff-Radford, Jonathan; Gunter, Jeffrey L.; Jones, David T.; Przybelski, Scott A.; Schwarz, Christopher G.; Huston, John; Lowe, Val; Elder, Benjamin D.; Machulda, Mary M.; Gunter, Nathaniel B.; Petersen, Ronald C.; Kantarci, Kejal; Vemuri, Prashanthi; Mielke, Michelle M.; Knopman, David S.; Graff-Radford, Neill R.; Jack, Clifford R.

In: Neurology, Vol. 93, No. 24, 10.12.2019, p. e2237-e2246.

Research output: Contribution to journalArticle

Graff-Radford, J, Gunter, JL, Jones, DT, Przybelski, SA, Schwarz, CG, Huston, J, Lowe, V, Elder, BD, Machulda, MM, Gunter, NB, Petersen, RC, Kantarci, K, Vemuri, P, Mielke, MM, Knopman, DS, Graff-Radford, NR & Jack, CR 2019, 'Cerebrospinal fluid dynamics disorders: Relationship to Alzheimer biomarkers and cognition', Neurology, vol. 93, no. 24, pp. e2237-e2246. https://doi.org/10.1212/WNL.0000000000008616
Graff-Radford J, Gunter JL, Jones DT, Przybelski SA, Schwarz CG, Huston J et al. Cerebrospinal fluid dynamics disorders: Relationship to Alzheimer biomarkers and cognition. Neurology. 2019 Dec 10;93(24):e2237-e2246. https://doi.org/10.1212/WNL.0000000000008616
Graff-Radford, Jonathan ; Gunter, Jeffrey L. ; Jones, David T. ; Przybelski, Scott A. ; Schwarz, Christopher G. ; Huston, John ; Lowe, Val ; Elder, Benjamin D. ; Machulda, Mary M. ; Gunter, Nathaniel B. ; Petersen, Ronald C. ; Kantarci, Kejal ; Vemuri, Prashanthi ; Mielke, Michelle M. ; Knopman, David S. ; Graff-Radford, Neill R. ; Jack, Clifford R. / Cerebrospinal fluid dynamics disorders : Relationship to Alzheimer biomarkers and cognition. In: Neurology. 2019 ; Vol. 93, No. 24. pp. e2237-e2246.
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abstract = "OBJECTIVE: To determine the frequency of high-convexity tight sulci (HCTS) in a population-based sample and whether the presence of HCTS and related features influenced participants' cognitive status and classification within the new Alzheimer-biomarker framework. METHODS: We analyzed 684 participants ≥50 years of age who were enrolled in the prospective population-based Mayo Clinic Study of Aging and underwent structural MRI, amyloid PET imaging, and tau PET imaging. A fully automated machine-learning algorithm that had been developed previously in house was used to detect neuroimaging features of HCTS. On the basis of PET and MRI measures, participants were classified as having normal (A-) or abnormal (A+) amyloid, normal (T-) or abnormal (T+) tau, and normal (N-) or abnormal (N+) neurodegeneration. The neuropsychological battery assessed domain-specific and global cognitive scores. Gait speed also was assessed. Analyses were adjusted for age and sex. RESULTS: Of 684 participants, 45 (6.6{\%}) were classified with HCTS according to the automated algorithm. Patients with HCTS were older than patients without HCTS (mean [SD] 78.0 [8.3] vs 71.9 [10.8] years; p < 0.001). More were cognitively impaired after age and sex adjustment (27{\%} vs 9{\%}; p = 0.005). Amyloid PET status was similar with and without HCTS, but tau PET standard uptake value ratio (SUVR) was lower for those with HCTS after age and sex adjustment (p < 0.001). Despite a lower tau SUVR, patients with HCTS had lower Alzheimer disease (AD) signature cortical thickness. With the amyloid-tau-neurodegeneration framework, HCTS was overrepresented in the T-(N)+ group, regardless of amyloid status. CONCLUSION: The HCTS pattern represents a definable subgroup of non-AD pathophysiology (i.e., T-[N]+) that is associated with cognitive impairment. HCTS may confound clinical and biomarker interpretation in AD clinical trials.",
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T2 - Relationship to Alzheimer biomarkers and cognition

AU - Graff-Radford, Jonathan

AU - Gunter, Jeffrey L.

AU - Jones, David T.

AU - Przybelski, Scott A.

AU - Schwarz, Christopher G.

AU - Huston, John

AU - Lowe, Val

AU - Elder, Benjamin D.

AU - Machulda, Mary M.

AU - Gunter, Nathaniel B.

AU - Petersen, Ronald C.

AU - Kantarci, Kejal

AU - Vemuri, Prashanthi

AU - Mielke, Michelle M.

AU - Knopman, David S.

AU - Graff-Radford, Neill R.

AU - Jack, Clifford R.

PY - 2019/12/10

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N2 - OBJECTIVE: To determine the frequency of high-convexity tight sulci (HCTS) in a population-based sample and whether the presence of HCTS and related features influenced participants' cognitive status and classification within the new Alzheimer-biomarker framework. METHODS: We analyzed 684 participants ≥50 years of age who were enrolled in the prospective population-based Mayo Clinic Study of Aging and underwent structural MRI, amyloid PET imaging, and tau PET imaging. A fully automated machine-learning algorithm that had been developed previously in house was used to detect neuroimaging features of HCTS. On the basis of PET and MRI measures, participants were classified as having normal (A-) or abnormal (A+) amyloid, normal (T-) or abnormal (T+) tau, and normal (N-) or abnormal (N+) neurodegeneration. The neuropsychological battery assessed domain-specific and global cognitive scores. Gait speed also was assessed. Analyses were adjusted for age and sex. RESULTS: Of 684 participants, 45 (6.6%) were classified with HCTS according to the automated algorithm. Patients with HCTS were older than patients without HCTS (mean [SD] 78.0 [8.3] vs 71.9 [10.8] years; p < 0.001). More were cognitively impaired after age and sex adjustment (27% vs 9%; p = 0.005). Amyloid PET status was similar with and without HCTS, but tau PET standard uptake value ratio (SUVR) was lower for those with HCTS after age and sex adjustment (p < 0.001). Despite a lower tau SUVR, patients with HCTS had lower Alzheimer disease (AD) signature cortical thickness. With the amyloid-tau-neurodegeneration framework, HCTS was overrepresented in the T-(N)+ group, regardless of amyloid status. CONCLUSION: The HCTS pattern represents a definable subgroup of non-AD pathophysiology (i.e., T-[N]+) that is associated with cognitive impairment. HCTS may confound clinical and biomarker interpretation in AD clinical trials.

AB - OBJECTIVE: To determine the frequency of high-convexity tight sulci (HCTS) in a population-based sample and whether the presence of HCTS and related features influenced participants' cognitive status and classification within the new Alzheimer-biomarker framework. METHODS: We analyzed 684 participants ≥50 years of age who were enrolled in the prospective population-based Mayo Clinic Study of Aging and underwent structural MRI, amyloid PET imaging, and tau PET imaging. A fully automated machine-learning algorithm that had been developed previously in house was used to detect neuroimaging features of HCTS. On the basis of PET and MRI measures, participants were classified as having normal (A-) or abnormal (A+) amyloid, normal (T-) or abnormal (T+) tau, and normal (N-) or abnormal (N+) neurodegeneration. The neuropsychological battery assessed domain-specific and global cognitive scores. Gait speed also was assessed. Analyses were adjusted for age and sex. RESULTS: Of 684 participants, 45 (6.6%) were classified with HCTS according to the automated algorithm. Patients with HCTS were older than patients without HCTS (mean [SD] 78.0 [8.3] vs 71.9 [10.8] years; p < 0.001). More were cognitively impaired after age and sex adjustment (27% vs 9%; p = 0.005). Amyloid PET status was similar with and without HCTS, but tau PET standard uptake value ratio (SUVR) was lower for those with HCTS after age and sex adjustment (p < 0.001). Despite a lower tau SUVR, patients with HCTS had lower Alzheimer disease (AD) signature cortical thickness. With the amyloid-tau-neurodegeneration framework, HCTS was overrepresented in the T-(N)+ group, regardless of amyloid status. CONCLUSION: The HCTS pattern represents a definable subgroup of non-AD pathophysiology (i.e., T-[N]+) that is associated with cognitive impairment. HCTS may confound clinical and biomarker interpretation in AD clinical trials.

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