Tau pathology and relative cerebral blood flow are independently associated with cognition in Alzheimer’s disease

Abstract Purpose We aimed to investigate associations between tau pathology and relative cerebral blood flow (rCBF), and their relationship with cognition in Alzheimer’s disease (AD), by using a single dynamic [18F]flortaucipir positron emission tomography (PET) scan. Methods Seventy-one subjects with AD (66 ± 8 years, mini-mental state examination (MMSE) 23 ± 4) underwent a dynamic 130-min [18F]flortaucipir PET scan. Cognitive assessment consisted of composite scores of four cognitive domains. For tau pathology and rCBF, receptor parametric mapping (cerebellar gray matter reference region) was used to create uncorrected and partial volume-corrected parametric images of non-displaceable binding potential (BPND) and R1, respectively. (Voxel-wise) linear regressions were used to investigate associations between BPND and/or R1 and cognition. Results Higher [18F]flortaucipir BPND was associated with lower R1 in the lateral temporal, parietal and occipital regions. Higher medial temporal BPND was associated with worse memory, and higher lateral temporal BPND with worse executive functioning and language. Higher parietal BPND was associated with worse executive functioning, language and attention, and higher occipital BPND with lower cognitive scores across all domains. Higher frontal BPND was associated with worse executive function and attention. For [18F]flortaucipir R1, lower values in the lateral temporal and parietal ROIs were associated with worse executive functioning, language and attention, and lower occipital R1 with lower language and attention scores. When [18F]flortaucipir BPND and R1 were modelled simultaneously, associations between lower R1 in the lateral temporal ROI and worse attention remained, as well as for lower parietal R1 and worse executive functioning and attention. Conclusion Tau pathology was associated with locally reduced rCBF. Tau pathology and low rCBF were both independently associated with worse cognitive performance. For tau pathology, these associations spanned widespread neocortex, while for rCBF, independent associations were restricted to lateral temporal and parietal regions and the executive functioning and attention domains. These findings indicate that each biomarker may independently contribute to cognitive impairment in AD.

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Autoregulation of Cerebral Blood Flow to Changes in Arterial Pressure in Mild Alzheimer's Disease

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.2010.135 ◽

2010 ◽

Vol 30 (11) ◽

pp. 1883-1889 ◽

Cited By ~ 17

Author(s):

Allyson R Zazulia ◽

Tom O Videen ◽

John C Morris ◽

William J Powers

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Blood Flow ◽

Cerebral Blood Flow ◽

Arterial Pressure ◽

The Elderly ◽

Local Defect ◽

Clinical Dementia Rating ◽

Positron Emission ◽

Before And After

Studies in transgenic mice overexpressing amyloid precursor protein (APP) demonstrate impaired autoregulation of cerebral blood flow (CBF) to changes in arterial pressure and suggest that cerebrovascular dysfunction may be critically important in the development of pathological Alzheimer's disease (AD). Given the relevance of such a finding for guiding hypertension treatment in the elderly, we assessed autoregulation in individuals with AD. Twenty persons aged 75±6 years with very mild or mild symptomatic AD (Clinical Dementia Rating 0.5 or 1.0) underwent 15O-positron emission tomography (PET) CBF measurements before and after mean arterial pressure (MAP) was lowered from 107±13 to 92±9 mm Hg with intravenous nicardipine; 11C-PIB-PET imaging and magnetic resonance imaging (MRI) were also obtained. There were no significant differences in mean CBF before and after MAP reduction in the bilateral hemispheres (−0.9±5.2 mL per 100 g per minute, P=0.4, 95% confidence interval (CI)=−3.4 to 1.5), cortical borderzones (−1.9±5.0 mL per 100 g per minute, P=0.10, 95% CI=−4.3 to 0.4), regions of T2W-MRI-defined leukoaraiosis (−0.3±4.4 mL per 100 g per minute, P=0.85, 95% CI=−3.3 to 3.9), or regions of peak 11C-PIB uptake (−2.5±7.7 mL per 100 g per minute, P=0.30, 95% CI=−7.7 to 2.7). The absence of significant change in CBF with a 10 to 15 mm Hg reduction in MAP within the normal autoregulatory range demonstrates that there is neither a generalized nor local defect of autoregulation in AD.

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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

European Journal of Nuclear Medicine and Molecular Imaging ◽

10.1007/s00259-021-05669-6 ◽

2022 ◽

Author(s):

Denise Visser ◽

Sander C. J. Verfaillie ◽

Emma E. Wolters ◽

Emma M. Coomans ◽

Tessa Timmers ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Blood Flow ◽

Cerebral Blood Flow ◽

Cognitive Deficits ◽

Early Onset ◽

Late Onset ◽

Age At Onset ◽

Region Of Interest ◽

Tau Pathology

Abstract 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.

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Cerebral blood flow abnormality in clinically diagnosed Alzheimer's disease patients with or without amyloid β accumulation on positron emission tomography

Neurology and Clinical Neuroscience ◽

10.1111/ncn3.12107 ◽

2016 ◽

Vol 5 (2) ◽

pp. 55-59 ◽

Cited By ~ 4

Author(s):

Toshikazu Mino ◽

Haruna Saito ◽

Jun Takeuchi ◽

Kazuhiro Ito ◽

Akitoshi Takeda ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Positron Emission Tomography ◽

Blood Flow ◽

Cerebral Blood Flow ◽

Amyloid Β ◽

Emission Tomography ◽

Positron Emission

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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

10.1101/2021.08.17.21262157 ◽

2021 ◽

Author(s):

Denise Visser ◽

Sander CJ Verfaillie ◽

Emma E Wolters ◽

Emma M Coomans ◽

Tessa Timmers ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Blood Flow ◽

Cerebral Blood Flow ◽

Cognitive Deficits ◽

Early Onset ◽

Late Onset ◽

Age At Onset ◽

Region Of Interest ◽

Tau Pathology

AbstractPurposeEarly-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.MethodsSeventy-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 minutes 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.ResultsBoth 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 occipito-parietal 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).ConclusionsCompared to LOAD, the degree of lateral temporal and occipito-parietal tau pathology and relative cerebral blood-flow is more strongly associated with cognition in EOAD.

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