Differential associations between neocortical tau pathology and blood flow with cognitive deficits in early-onset vs late-onset Alzheimer’s disease

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Differential associations between neocortical tau pathology and blood flow with cognitive deficits in early-onset vs late-onset Alzheimer’s disease

Visser, Denise (author): Vrije Universiteit Amsterdam

Verfaillie, Sander C.J. (author): Vrije Universiteit Amsterdam

Wolters, Emma E. (author): Vrije Universiteit Amsterdam

Coomans, Emma M. (author): Vrije Universiteit Amsterdam

Timmers, Tessa (author): Vrije Universiteit Amsterdam

Tuncel, Hayel (author): Vrije Universiteit Amsterdam

Boellaard, Ronald (author): Vrije Universiteit Amsterdam

Golla, Sandeep S.V. (author): Vrije Universiteit Amsterdam

Windhorst, Albert D. (author): Vrije Universiteit Amsterdam

Scheltens, Philip (author): Vrije Universiteit Amsterdam

van der Flier, Wiesje M. (author): Vrije Universiteit Amsterdam

van Berckel, Bart N.M. (author): Vrije Universiteit Amsterdam

Ossenkoppele, Rik (author): Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups,Vrije Universiteit Amsterdam

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2022-01-08
2022
English.
In: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 49:6, s. 1951-1963

Related links:: http://dx.doi.org/10... (free); show more...; https://link.springe...; https://lup.lub.lu.s...; https://doi.org/10.1...; show less...

Journal article (peer-reviewed)

Abstract Subject headings

Purpose: Early-onset Alzheimer’s disease (EOAD) and late-onset Alzheimer’s disease (LOAD) differ in neuropathological burden and type of cognitive deficits. Assessing tau pathology and relative cerebral blood flow (rCBF) measured with [18F]flortaucipir PET in relation to cognition may help explain these differences between EOAD and LOAD. Methods: Seventy-nine amyloid-positive individuals with a clinical diagnosis of AD (EOAD: n = 35, age-at-PET = 59 ± 5, MMSE = 23 ± 4; LOAD: n = 44, age-at-PET = 71 ± 5, MMSE = 23 ± 4) underwent a 130-min dynamic [18F]flortaucipir PET scan and extensive neuropsychological assessment. We extracted binding potentials (BPND) and R1 (proxy of rCBF) from parametric images using receptor parametric mapping, in medial and lateral temporal, parietal, occipital, and frontal regions-of-interest and used nine neuropsychological tests covering memory, attention, language, and executive functioning. We first examined differences between EOAD and LOAD in BPND or R1 using ANOVA (region-of-interest analysis) and voxel-wise contrasts. Next, we performed linear regression models to test for potential interaction effects between age-at-onset and BPND/R1 on cognition. Results: Both region-of-interest and voxel-wise contrasts showed higher [18F]flortaucipir BPND values across all neocortical regions in EOAD. By contrast, LOAD patients had lower R1 values (indicative of more reduced rCBF) in medial temporal regions. For both tau and flow in lateral temporal, and occipitoparietal regions, associations with cognitive impairment were stronger in EOAD than in LOAD (EOAD BPND − 0.76 ≤ stβ ≤ − 0.48 vs LOAD − 0.18 ≤ stβ ≤ − 0.02; EOAD R1 0.37 ≤ stβ ≤ 0.84 vs LOAD − 0.25 ≤ stβ ≤ 0.16). Conclusions: Compared to LOAD, the degree of lateral temporal and occipitoparietal tau pathology and relative cerebral blood-flow is more strongly associated with cognition in EOAD.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Neurologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Neurology (hsv//eng)

Keyword

Alzheimer’s disease
Cerebral blood flow
Cognition
Early-onset
Tau pathology
[F]flortaucipir

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By the author/editor: Visser, Denise; Verfaillie, Sand ...; Wolters, Emma E.; Coomans, Emma M.; Timmers, Tessa; Tuncel, Hayel; show more...; Boellaard, Ronal ...; Golla, Sandeep S ...; Windhorst, Alber ...; Scheltens, Phili ...; van der Flier, W ...; van Berckel, Bar ...; Ossenkoppele, Ri ...; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Neurology

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By the university: Lund University

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