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The investigators will conduct tau positron emission tomography (PET) scans on 125 adults using the radiopharmaceutical Flortaucipir F18 ([18F]AV-1451). This will allow the investigators to determine tau deposition across adults of different ages and assess the relationship of current tau burden to cognitive function and amyloid deposition collected over the previous 10-year interval.
Alzheimer's disease (AD) is a highly prevalent disorder of dementia in older adults. AD neuropathology is marked by the presence of amyloid plaques and tau neurofibrillary tangles. Autopsy studies, as well as magnetic resonance imaging (MRI) studies in living persons, have established that the neurodegenerative changes in AD begin in medial temporal lobe structures and later progress to adjacent temporal, parietal and frontal neocortical regions. Magnetic resonance image studies of AD consistently reveal volumetric loss in the hippocampus using both cross-sectional and longitudinal approaches. The primary symptom of early-stage AD is memory impairment possibly accompanied by deficits in attentional control. Normal aging, however, is also marked by cognitive decline, as well as structural brain changes. Autopsy data had shown in the past that about 30% of older adults with no obvious cognitive impairment show some degree of the neuropathology typically associated with dementia at autopsy.
Importantly, the recent ability to image beta-amyloid and tau deposits in vivo using positron emission tomography (PET) scanning has revolutionized our understanding of early stages of AD. Evidence suggests that amyloid deposits may be detected 10 - 15 years before memory symptoms appear. These findings are leading to the ability to diagnose AD years before symptoms begin. Much less is known about the impact and developmental course of tau deposition as compared to beta-amyloid because the ligand to image tau was only recently invented. There is increasing evidence that tau is particularly toxic to the brain and is a later precursor of AD than amyloid deposits. Additional research on beta-amyloid and tau deposition in aging is crucial, as much work suggests that treatment of AD may be most effective when implemented early in the time course of the disease. Understanding the impact of tau deposits and its interactions with amyloid deposition allows the investigators to see the development of early markers of AD, which are important in understanding the trajectory of the disease. An important approach to understand the amyloid/tau puzzle and its relationship to AD is a large-scale longitudinal study of normal aging that integrates extensive neuroimaging and cognitive assessments along with tau imaging. A key aspect in understanding pathological aging is the need to be able to clearly differentiate normal aging from early pathology. The present Tau imaging study described here is an important component of the Dallas Lifetime Brain Study (DLBS).
The Dallas Lifespan Brain Study (DLBS) began in 2008 and was designed to utilize the new in vivo imaging techniques to address uncertainty regarding how AD pathology relates to the developmental process of aging and cognition, fueled in part by the partial overlap of pathological markers and decline in mnemonic function observed in a substantial proportion of 'normal' aged individuals. A total of 296 participants were recruited for Wave 1 from 2008 to 2014 to the DLBS and they received cognitive testing, structural and functional MRI, as well as a scan for beta amyloid using the radioligand AV-45 Florbetapir F 18 (also known as "[18F]AV-45"). A total of 183 returning participants were tested four years later in Wave 2, and they received the same battery as in Wave 1. In addition, 60 of these were also scanned with Flortaucipir F 18 (also known as "[18F]AV-1451"). [18F]AV-1451 is a newly-developed Phase II ligand that measures tau deposit in the human brain and this drug was provided to the DLBS by Avid Radiopharmaceuticals.
The objective of the current study is to test 125 DLBS participants with [18F]AV-1451 (Flortaucipir F 18) at the University of Texas Southwestern Medical Center (UTSW). The inclusion of tau imaging in Wave 3 will allow the investigators to relate tau deposition in the brain to the 10-year history of amyloid deposition and cognitive decline in the DLBS participants and understand the independent and joint contributions of tau to cognitive decline and early AD at different ages.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Follow up DLBS participants | Experimental | Eight to ten year follow-up DLBS participants who were cognitively normal at the time of enrollment from 2008 to 2014. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| [18F]AV-1451 | Drug | The subject will receive up to a target dose of 370 megabecquerel (MBq) as a single IV bolus of [18F]AV-1451. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Standardized Uptake Value Ratios (SUVrs) Calculated From [18F]AV-1451 PET Scans | Tau accumulation in the temporal lobe will be measured as the standardized uptake value ratio (SUVR) computed from each participant's [18F]AV-1451 PET scans averaged across six bilateral regions of interest (ROls) by normalizing regional counts to the whole cerebellum. The 6 ROls are: inferior temporal gyrus, middle temporal gyrus, superior temporal gyrus, entorhinal cortex, parahippocampal gyrus, and fusiform gyrus. Each participant's PET scan and the six bilateral ROIs will be coregistered to their T1-weighted MRI (MP-RAGE). Finally, the mean observed tracer count from each region will be extracted and normalized using whole cerebellum as the reference. Observed tau SUVR scores in humans range from 0.5 to 2.5, with higher scores being indicative of greater tau accumulation. Unless otherwise specified, all subsequent analyses will use this temporal tau SUVR and will involve examination of cross-sectional relationships between tau SUVR and key outcome measures at Wave 3 of the DLBS. | An average of 3-months post-PET study visit |
| Measure | Description | Time Frame |
|---|---|---|
| Relationship of Tau Burden to Episodic Memory Function | Episodic memory is a construct that measures how well individuals can store, maintain, and retrieve detailed information in long-term memory. Episodic memory will be a composite score using the Hopkins Verbal Learning test with 3 subcomponents (immediate recall: range 0-12, delayed recall: range 0-12, and recognition: range 0-24) and the immediate recall of the CANTAB Verbal Recognition Memory task (range 0-12). Scores from the tasks will be converted to Z-scores and averaged to form an episodic memory composite, and then this final value with be converted to a Z-score. A higher composite Z-score indicates better episodic memory, a Z-score of 0 represents the population mean, and all Z-scores have a standard deviation of 1. Values in this table represent this Episodic Memory Z-score. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Denise Park, PhD | The University of Texas at Dallas | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UT Southwestern Medical Center | Dallas | Texas | 75390 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| Background | Balota D.A., Faust M.E. (2001). Attention in dementia of the Alzheimer's type. In: Boller F, Cappa S, editors. Handbook of Neuropsychology. 2nd Ed. NY: Elsevier Science; pp. 51-80. | ||
| 16632311 | Background | Bennett DA, Schneider JA, Tang Y, Arnold SE, Wilson RS. The effect of social networks on the relation between Alzheimer's disease pathology and level of cognitive function in old people: a longitudinal cohort study. Lancet Neurol. 2006 May;5(5):406-12. doi: 10.1016/S1474-4422(06)70417-3. | |
| 1759558 |
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Scans were acquired from participants previously enrolled in Wave 1 or 2 of the Dallas Lifespan Brain Study (DLBS)
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| ID | Title | Description |
|---|---|---|
| FG000 | Follow up DLBS Participants | Eight to ten year follow-up DLBS participants who were cognitively normal at the time of enrollment from 2008 to 2014. [18F]AV-1451: The subject will receive up to a target dose of 370 megabecquerel (MBq) as a single IV bolus of [18F]AV-1451. Positron Emission Tomography: Approximately 80 minutes after injection subjects will be placed in the University of Texas Southwestern Medical Center (UTSW) Positron Emission Tomography/Computed Tomography (PET/CT) scanner for a 20-minute brain scan. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Follow up DLBS Participants | Eight to ten year follow-up DLBS participants who were cognitively normal at the time of enrollment from 2008 to 2014. [18F]AV-1451: The subject will receive up to a target dose of 370 megabecquerel (MBq) as a single IV bolus of [18F]AV-1451. Positron Emission Tomography: Approximately 80 minutes after injection subjects will be placed in the UTSW PET/CT scanner for a 20-minute brain scan. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Standardized Uptake Value Ratios (SUVrs) Calculated From [18F]AV-1451 PET Scans | Tau accumulation in the temporal lobe will be measured as the standardized uptake value ratio (SUVR) computed from each participant's [18F]AV-1451 PET scans averaged across six bilateral regions of interest (ROls) by normalizing regional counts to the whole cerebellum. The 6 ROls are: inferior temporal gyrus, middle temporal gyrus, superior temporal gyrus, entorhinal cortex, parahippocampal gyrus, and fusiform gyrus. Each participant's PET scan and the six bilateral ROIs will be coregistered to their T1-weighted MRI (MP-RAGE). Finally, the mean observed tracer count from each region will be extracted and normalized using whole cerebellum as the reference. Observed tau SUVR scores in humans range from 0.5 to 2.5, with higher scores being indicative of greater tau accumulation. Unless otherwise specified, all subsequent analyses will use this temporal tau SUVR and will involve examination of cross-sectional relationships between tau SUVR and key outcome measures at Wave 3 of the DLBS. | Participants with available data were analyzed. This sample excludes one participant whose scanner data were unusable due to technical issues during acquisition. | Posted | Mean | Standard Deviation | standardized uptake value ratio | An average of 3-months post-PET study visit |
Day of visit (post-injection, pre-discharge) and follow-up call 48-72 hours post-injection
The experimenter inquired about adverse events (AEs) during the time frames described above and, if AEs were reported, they filled out a log indicating the date/time, severity (mild, moderate, severe), possible relation to drug/procedure, action taken, and event resolution (e.g., resolved, ongoing).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Follow up DLBS Participants | Eight to ten year follow-up DLBS participants who were cognitively normal at the time of enrollment from 2008 to 2014. [18F]AV-1451: The subject will receive up to a target dose of 370 megabecquerel (MBq) as a single IV bolus of [18F]AV-1451. Positron Emission Tomography: Approximately 80 minutes after injection subjects will be placed in the UTSW PET/CT scanner for a 20-minute brain scan. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Elevated blood pressure | Blood and lymphatic system disorders | CTCAE v5 | Systematic Assessment | AE resolved by 48-72 hour follow-up call. |
Although several of these participants had an earlier PET-tau scan and we originally proposed to analyze longitudinal effects of tauopathy, a new PET scanner was implemented for this final wave of PET-tau data collection; preliminary analyses and discussions indicated the two scanners were not comparable and so we opted to focus on only this final wave of PET-tau data.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Joseph Hennessee | The University of Texas at Dallas | 408-813-4488 | joseph.hennessee@utdallas.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Nov 18, 2021 | Feb 9, 2023 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Apr 20, 2022 | Feb 9, 2023 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D000544 | Alzheimer Disease |
| D060825 | Cognitive Dysfunction |
| ID | Term |
|---|---|
| D003704 | Dementia |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| C000591008 | 7-(6-fluoropyridin-3-yl)-5H-pyrido(4,3-b)indole |
| D009682 | Magnetic Resonance Spectroscopy |
| ID | Term |
|---|---|
| D013057 | Spectrum Analysis |
| D002623 | Chemistry Techniques, Analytical |
| D008919 | Investigative Techniques |
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| Positron Emission Tomography | Procedure | Approximately 80 minutes after injection subjects will be placed in the UTSW PET/CT scanner for a 20-minute brain scan. |
|
|
| 1-year post study completion |
| Relationship of Amyloid Accumulation to Tau Burden | Amyloid accumulation throughout the Dallas Lifespan Brain Study (6-9.8 years) will be measured with Florbetapir F18 and calculated as an Amyloid Standard Uptake Value ratio (SUVR) by normalizing regional counts to the whole cerebellum. Amyloid SUVR scores will be averaged across eight cortical regions spanning most of the cortex: dorsal lateral prefrontal cortex, orbitofrontal cortex, lateral parietal cortex, posterior cingulate cortex, anterior cingulate cortex, precuneus, lateral temporal cortex, and lateral occipital lobe. Amyloid SUVR scores observed in this study have ranged from 0.88 to 1.74, with higher scores being indicative of greater amyloid accumulation. Finally, annualized change scores for these amyloid SUVRs across the full study duration (6-9.8 years) will be calculated to determine the extent that the rate of amyloid accumulation relates to tau burden at the end of the study. | 1-year post study completion |
| Relationship of Tau Burden to Speed of Processing | Speed of processing is a construct that measures how rapidly individuals can process information. To assess speed of processing, a composite score will be created using the Digit Comparison task and the Wechsler Adult Intelligence Scale (WAIS) Digit Symbol task. Observed DLBS raw scores range from 27 to 116 for Digit Comparison task and 20 to 90 for Digit Symbol task. Participants' raw scores are converted to Z-scores and averaged to form a speed of processing composite, and then this final value with be converted to a Z-score. A higher composite Z-score indicates better speed of processing, a Z-score of 0 represents the population mean, and all Z-scores have a standard deviation of 1. Values in this table represent this Speed of Processing Z-score. | 1-year post study completion |
| Relationship of Tau Burden to Reasoning | The construct of reasoning measures an individual's ability to recognize novel patterns and the conceptual relationship among objects and effectively apply these patterns to solve similar problems. To assess reasoning, a composite score will be created using the Raven's Progressive Matrices task and Educational Testing Service (ETS) Letters Sets task. Observed DLBS raw scores range from 9 to 30 for Raven's Progressive Matrices task and from 0.5 to 30 for ETS Letters Sets task. Raven's Progress Matrices and ETS Letter Sets will be converted to Z-scores and averaged to form a reasoning composite, and then this final value with be converted to a Z-score. A higher composite Z-score indicates higher reasoning ability, a Z-score of 0 represents the population mean, and all Z-scores have a standard deviation of 1. Values in this table represent this Reasoning Z-score. | 1-year post study completion |
| Relationship of Tau Burden to Working Memory | Working memory is a construct that measures the ability of individuals to simultaneously manipulate and store information. To assess working memory, a composite score will be created using the CANTAB Spatial Working Memory task (reverse scored) and the Wechsler Adult Intelligence Scale (WAIS-III) Letter Number Sequencing task. Observed DLBS raw scores range from 0 to 86 total errors for the CANTAB Spatial Working Memory task and 2 to 20 for the WAIS-III Letter Number Sequencing task. Participants' raw scores are converted to Z-scores and averaged to form a working memory composite, and then this final value with be converted to a Z-score. A higher working memory composite Z-score indicates better working memory, a Z-score of 0 represents the population mean, and all Z-scores have a standard deviation of 1. Values in this table represent this Working Memory Z-score. | 1-year post study completion |
| Relationship of Tau Burden to Participants' Age | Linear regressions between the AV-1451 SUVR in each of the temporal regions of interest with participant age will be calculated, and in additional analyses, non-linear effects of age will be examined via quadratic and growth modeling. Observed AV-1451 SUVR scores in humans have ranged from 0.5 to 2.5, with higher scores being indicative of greater tau accumulation. The investigators predict that tau accumulation will accelerate in old age, thus supporting a non-linear rate of deposition. | 1-year post study completion |
| Relationship of Tau Burden to Cortical Thickness | Regional cortical thickness will be estimated from previously acquired T1-weighted structural magnetic resonance imaging (MRl) scans using FreeSurfer (ver. 5.3), with surface parcellation manually edited when necessary by our team of experts. The regions selected for analyses of cortical thickness were the ROIs used to estimate temporal tau SUVR: inferior temporal gyrus, middle temporal gyrus, superior temporal gyrus, entorhinal cortex, parahippocampal gyrus, and fusiform gyrus. Observed cortical thickness in these regions range from 1.38 to 3.83 mm with higher scores indicating greater thickness. | 1-year post study completion |
| Relationship of Tau Burden to Hippocampal Volume | Hippocampal volume will be estimated from previously acquired T1-weighted structural magnetic resonance imaging (MRl) scans using FreeSurfer (ver. 5.3), with surface parcellation manually edited when necessary by our team of experts. This region was selected for analysis as it was one of the ROIs used to estimate temporal tau SUVR. Observed DLBS hippocampal volume ranged from 1843 to 5342 mm^3 with higher scores indicating greater volume. | 1-year post study completion |
| Relationship of Tau Burden to White Matter Integrity | White matter integrity will be assessed using the estimated volume of white matter hypointensities from previously acquired T1-weighted structural magnetic resonance imaging (MRl) scans using FreeSurfer (ver. 5.3). Observed DLBS white matter hypointensities range from 796 to 35,037 mm^3 with higher scores indicating greater volume of hypointensities and reflecting worse white matter integrity. | 1-year post study completion |
| Relationship of Tau Burden to Functional Magnetic Resonance Imaging (MRI) | For functional measures, blood oxygenation level dependent signal from contrasts of interest using selected ROls will be created. For the semantic judgment task (easy judgments - fixation), the investigators will focus on ROIs associated with processing meaning, including inferior frontal gyrus, precuneus, and middle temporal gyrus. Observed BOLD activation values (betas) ranged from -1.00 to 1.30 with higher values indicating greater activation. | 1-year post study completion |
| Relationship of Tau Burden to Resting-State Brain System Segregation | Resting-state brain system segregation was computed on data collected from a separate resting-state scan using graph theory. System segregation is calculated as (Zw - Zb) / Zw, where Zw is the mean Fisher z-transformed r between nodes with the same system and Zb is the mean Fisher z-transformed r between nodes of one system to all nodes in other systems. Higher values indicate reduced node-node connectivity between systems relative to within-system connectivity. A score of 0 would reflect equal resting-state connectivity between nodes within the same functional system and between nodes of separate systems. Like all Z-scores, these scores typically range from -3 to 3. Higher scores are observed in younger adults than in older adults and may suggest a more youth-like brain, though higher scores are not objectively better. Systems were defined based on Power et al., (2011, Neuron) and more details on this measure are described in Chan et al. (2014, PNAS). | 1-year post study completion |
| Background |
| Braak H, Braak E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol. 1991;82(4):239-59. doi: 10.1007/BF00308809. |
| 8234547 | Background | Convit A, de Leon MJ, Golomb J, George AE, Tarshish CY, Bobinski M, Tsui W, De Santi S, Wegiel J, Wisniewski H. Hippocampal atrophy in early Alzheimer's disease: anatomic specificity and validation. Psychiatr Q. 1993 Winter;64(4):371-87. doi: 10.1007/BF01064929. |
| Background | Holm S: A Simple Sequentially Rejective Bonferroni Test. Scandinavian Journal of Statistics. 1979, 65 -670. |
| 8056947 | Background | Kemper S, Anagnopoulos C, Lyons K, Heberlein W. Speech accommodations to dementia. J Gerontol. 1994 Sep;49(5):P223-9. doi: 10.1093/geronj/49.5.p223. |
| 2864910 | Background | Khachaturian ZS. Diagnosis of Alzheimer's disease. Arch Neurol. 1985 Nov;42(11):1097-105. doi: 10.1001/archneur.1985.04060100083029. No abstract available. |
| 8363449 | Background | Killiany RJ, Moss MB, Albert MS, Sandor T, Tieman J, Jolesz F. Temporal lobe regions on magnetic resonance imaging identify patients with early Alzheimer's disease. Arch Neurol. 1993 Sep;50(9):949-54. doi: 10.1001/archneur.1993.00540090052010. |
| Background | Jack, C., Knopman, D., Jagust, W., Petersen, R., Weiner, M., Aisen, P., … Trojanowski, J. (2013). Update on hypothetical model of Alzheimer's disease biomarkers. Alzheimer's & Dementia, 9(4), 521-522. |
| 9305341 | Background | Jack CR Jr, Petersen RC, Xu YC, Waring SC, O'Brien PC, Tangalos EG, Smith GE, Ivnik RJ, Kokmen E. Medial temporal atrophy on MRI in normal aging and very mild Alzheimer's disease. Neurology. 1997 Sep;49(3):786-94. doi: 10.1212/wnl.49.3.786. |
| 9707301 | Background | Mohs RC, Ashman TA, Jantzen K, Albert M, Brandt J, Gordon B, Rasmusson X, Grossman M, Jacobs D, Stern Y. A study of the efficacy of a comprehensive memory enhancement program in healthy elderly persons. Psychiatry Res. 1998 Feb 27;77(3):183-95. doi: 10.1016/s0165-1781(98)00003-1. |
| 19035823 | Background | Park DC, Reuter-Lorenz P. The adaptive brain: aging and neurocognitive scaffolding. Annu Rev Psychol. 2009;60:173-96. doi: 10.1146/annurev.psych.59.103006.093656. |
| 11559310 | Background | Price JL, Ko AI, Wade MJ, Tsou SK, McKeel DW, Morris JC. Neuron number in the entorhinal cortex and CA1 in preclinical Alzheimer disease. Arch Neurol. 2001 Sep;58(9):1395-402. doi: 10.1001/archneur.58.9.1395. |
| 25143069 | Background | Reuter-Lorenz PA, Park DC. How does it STAC up? Revisiting the scaffolding theory of aging and cognition. Neuropsychol Rev. 2014 Sep;24(3):355-70. doi: 10.1007/s11065-014-9270-9. Epub 2014 Aug 21. |
| 21514248 | Background | Sperling RA, Aisen PS, Beckett LA, Bennett DA, Craft S, Fagan AM, Iwatsubo T, Jack CR Jr, Kaye J, Montine TJ, Park DC, Reiman EM, Rowe CC, Siemers E, Stern Y, Yaffe K, Carrillo MC, Thies B, Morrison-Bogorad M, Wagster MV, Phelps CH. Toward defining the preclinical stages of Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011 May;7(3):280-92. doi: 10.1016/j.jalz.2011.03.003. Epub 2011 Apr 21. |
| 12370458 | Background | Storandt M, Grant EA, Miller JP, Morris JC. Rates of progression in mild cognitive impairment and early Alzheimer's disease. Neurology. 2002 Oct 8;59(7):1034-41. doi: 10.1212/wnl.59.7.1034. |
| 9330990 | Background | Trojanowski JQ, Clark CM, Schmidt ML, Arnold SE, Lee VM. Strategies for improving the postmortem neuropathological diagnosis of Alzheimer's disease. Neurobiol Aging. 1997 Jul-Aug;18(4 Suppl):S75-9. doi: 10.1016/s0197-4580(97)00075-4. |
| 12411259 | Background | Whalley LJ. Brain ageing and dementia: what makes the difference? Br J Psychiatry. 2002 Nov;181:369-71. doi: 10.1192/bjp.181.5.369. No abstract available. |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Education, Continuous | Mean | Standard Deviation | years |
|
| Mini-Mental State Examination | The Mini-Mental State Examination (MMSE) is a simple pen-and-paper test of cognitive function. The total score is reported (range: 0-30 points) and higher scores on the MMSE reflect better cognitive function. | Mean | Standard Deviation | units on a scale |
|
| ID | Title | Description |
|---|---|---|
| OG000 | Follow up DLBS Participants | Eight to ten year follow-up DLBS participants who were cognitively normal at the time of enrollment from 2008 to 2014. [18F]AV-1451: The subject will receive up to a target dose of 370 megabecquerel (MBq) as a single IV bolus of [18F]AV-1451. Positron Emission Tomography: Approximately 80 minutes after injection subjects will be placed in the UTSW PET/CT scanner for a 20-minute brain scan. |
|
|
| Secondary | Relationship of Tau Burden to Episodic Memory Function | Episodic memory is a construct that measures how well individuals can store, maintain, and retrieve detailed information in long-term memory. Episodic memory will be a composite score using the Hopkins Verbal Learning test with 3 subcomponents (immediate recall: range 0-12, delayed recall: range 0-12, and recognition: range 0-24) and the immediate recall of the CANTAB Verbal Recognition Memory task (range 0-12). Scores from the tasks will be converted to Z-scores and averaged to form an episodic memory composite, and then this final value with be converted to a Z-score. A higher composite Z-score indicates better episodic memory, a Z-score of 0 represents the population mean, and all Z-scores have a standard deviation of 1. Values in this table represent this Episodic Memory Z-score. | Participants with available data were analyzed. This sample excludes one participant whose scanner data were unusable due to technical issues during acquisition. | Posted | Mean | Standard Deviation | Z-score | 1-year post study completion |
|
|
|
|
| Secondary | Relationship of Amyloid Accumulation to Tau Burden | Amyloid accumulation throughout the Dallas Lifespan Brain Study (6-9.8 years) will be measured with Florbetapir F18 and calculated as an Amyloid Standard Uptake Value ratio (SUVR) by normalizing regional counts to the whole cerebellum. Amyloid SUVR scores will be averaged across eight cortical regions spanning most of the cortex: dorsal lateral prefrontal cortex, orbitofrontal cortex, lateral parietal cortex, posterior cingulate cortex, anterior cingulate cortex, precuneus, lateral temporal cortex, and lateral occipital lobe. Amyloid SUVR scores observed in this study have ranged from 0.88 to 1.74, with higher scores being indicative of greater amyloid accumulation. Finally, annualized change scores for these amyloid SUVRs across the full study duration (6-9.8 years) will be calculated to determine the extent that the rate of amyloid accumulation relates to tau burden at the end of the study. | Participants with available data were analyzed. | Posted | Mean | Standard Deviation | standardized uptake value ratio | 1-year post study completion |
|
|
|
|
| Secondary | Relationship of Tau Burden to Speed of Processing | Speed of processing is a construct that measures how rapidly individuals can process information. To assess speed of processing, a composite score will be created using the Digit Comparison task and the Wechsler Adult Intelligence Scale (WAIS) Digit Symbol task. Observed DLBS raw scores range from 27 to 116 for Digit Comparison task and 20 to 90 for Digit Symbol task. Participants' raw scores are converted to Z-scores and averaged to form a speed of processing composite, and then this final value with be converted to a Z-score. A higher composite Z-score indicates better speed of processing, a Z-score of 0 represents the population mean, and all Z-scores have a standard deviation of 1. Values in this table represent this Speed of Processing Z-score. | Participants with available data were analyzed. This sample excludes one participant whose scanner data were unusable due to technical issues during acquisition. | Posted | Mean | Standard Deviation | Z-score | 1-year post study completion |
|
|
|
|
| Secondary | Relationship of Tau Burden to Reasoning | The construct of reasoning measures an individual's ability to recognize novel patterns and the conceptual relationship among objects and effectively apply these patterns to solve similar problems. To assess reasoning, a composite score will be created using the Raven's Progressive Matrices task and Educational Testing Service (ETS) Letters Sets task. Observed DLBS raw scores range from 9 to 30 for Raven's Progressive Matrices task and from 0.5 to 30 for ETS Letters Sets task. Raven's Progress Matrices and ETS Letter Sets will be converted to Z-scores and averaged to form a reasoning composite, and then this final value with be converted to a Z-score. A higher composite Z-score indicates higher reasoning ability, a Z-score of 0 represents the population mean, and all Z-scores have a standard deviation of 1. Values in this table represent this Reasoning Z-score. | Participants with available data were analyzed. This sample excludes one participant whose scanner data were unusable due to technical issues during acquisition. | Posted | Mean | Standard Deviation | Z-scores | 1-year post study completion |
|
|
|
|
| Secondary | Relationship of Tau Burden to Working Memory | Working memory is a construct that measures the ability of individuals to simultaneously manipulate and store information. To assess working memory, a composite score will be created using the CANTAB Spatial Working Memory task (reverse scored) and the Wechsler Adult Intelligence Scale (WAIS-III) Letter Number Sequencing task. Observed DLBS raw scores range from 0 to 86 total errors for the CANTAB Spatial Working Memory task and 2 to 20 for the WAIS-III Letter Number Sequencing task. Participants' raw scores are converted to Z-scores and averaged to form a working memory composite, and then this final value with be converted to a Z-score. A higher working memory composite Z-score indicates better working memory, a Z-score of 0 represents the population mean, and all Z-scores have a standard deviation of 1. Values in this table represent this Working Memory Z-score. | Participants with available data were analyzed. This sample excludes one participant whose scanner data were unusable due to technical issues during acquisition. | Posted | Mean | Standard Deviation | Z-score | 1-year post study completion |
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| Secondary | Relationship of Tau Burden to Participants' Age | Linear regressions between the AV-1451 SUVR in each of the temporal regions of interest with participant age will be calculated, and in additional analyses, non-linear effects of age will be examined via quadratic and growth modeling. Observed AV-1451 SUVR scores in humans have ranged from 0.5 to 2.5, with higher scores being indicative of greater tau accumulation. The investigators predict that tau accumulation will accelerate in old age, thus supporting a non-linear rate of deposition. | Participants with available data were analyzed. This sample excludes one participant whose scanner data were unusable due to technical issues during acquisition. | Posted | Mean | Standard Deviation | standardized uptake value ratio | 1-year post study completion |
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| Secondary | Relationship of Tau Burden to Cortical Thickness | Regional cortical thickness will be estimated from previously acquired T1-weighted structural magnetic resonance imaging (MRl) scans using FreeSurfer (ver. 5.3), with surface parcellation manually edited when necessary by our team of experts. The regions selected for analyses of cortical thickness were the ROIs used to estimate temporal tau SUVR: inferior temporal gyrus, middle temporal gyrus, superior temporal gyrus, entorhinal cortex, parahippocampal gyrus, and fusiform gyrus. Observed cortical thickness in these regions range from 1.38 to 3.83 mm with higher scores indicating greater thickness. | Participants with available data were analyzed. This sample excludes one participant whose scanner data were unusable due to technical issues during acquisition and three participants did not have a recent MRI. | Posted | Mean | Standard Deviation | mm | 1-year post study completion |
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| Secondary | Relationship of Tau Burden to Hippocampal Volume | Hippocampal volume will be estimated from previously acquired T1-weighted structural magnetic resonance imaging (MRl) scans using FreeSurfer (ver. 5.3), with surface parcellation manually edited when necessary by our team of experts. This region was selected for analysis as it was one of the ROIs used to estimate temporal tau SUVR. Observed DLBS hippocampal volume ranged from 1843 to 5342 mm^3 with higher scores indicating greater volume. | Participants with available data were analyzed. This sample excludes one participant whose scanner data were unusable due to technical issues during acquisition and three participants did not have a recent MRI. | Posted | Mean | Standard Deviation | mm^3 | 1-year post study completion |
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| Secondary | Relationship of Tau Burden to White Matter Integrity | White matter integrity will be assessed using the estimated volume of white matter hypointensities from previously acquired T1-weighted structural magnetic resonance imaging (MRl) scans using FreeSurfer (ver. 5.3). Observed DLBS white matter hypointensities range from 796 to 35,037 mm^3 with higher scores indicating greater volume of hypointensities and reflecting worse white matter integrity. | Participants with available data were analyzed. This sample excludes one participant whose scanner data were unusable due to technical issues during acquisition and three participants who did not have a recent MRI. | Posted | Mean | Standard Deviation | mm^3 | 1-year post study completion |
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| Secondary | Relationship of Tau Burden to Functional Magnetic Resonance Imaging (MRI) | For functional measures, blood oxygenation level dependent signal from contrasts of interest using selected ROls will be created. For the semantic judgment task (easy judgments - fixation), the investigators will focus on ROIs associated with processing meaning, including inferior frontal gyrus, precuneus, and middle temporal gyrus. Observed BOLD activation values (betas) ranged from -1.00 to 1.30 with higher values indicating greater activation. | Participants with available tau and fMRI data were analyzed. | Posted | Mean | Standard Deviation | fMRI activation beta | 1-year post study completion |
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| Secondary | Relationship of Tau Burden to Resting-State Brain System Segregation | Resting-state brain system segregation was computed on data collected from a separate resting-state scan using graph theory. System segregation is calculated as (Zw - Zb) / Zw, where Zw is the mean Fisher z-transformed r between nodes with the same system and Zb is the mean Fisher z-transformed r between nodes of one system to all nodes in other systems. Higher values indicate reduced node-node connectivity between systems relative to within-system connectivity. A score of 0 would reflect equal resting-state connectivity between nodes within the same functional system and between nodes of separate systems. Like all Z-scores, these scores typically range from -3 to 3. Higher scores are observed in younger adults than in older adults and may suggest a more youth-like brain, though higher scores are not objectively better. Systems were defined based on Power et al., (2011, Neuron) and more details on this measure are described in Chan et al. (2014, PNAS). | Participants with available data were analyzed. This sample excluded 2 statistical outliers. | Posted | Mean | Standard Deviation | Z-score | 1-year post study completion |
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| 0 |
| 125 |
| 0 |
| 125 |
| 13 |
| 125 |
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| Black dot in visual field | Eye disorders | CTCAE v5 | Systematic Assessment | AE resolved by 48-72 hour follow-up call. |
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| Muscle soreness in injection arm | Musculoskeletal and connective tissue disorders | CTCAE v5 | Systematic Assessment | AE resolved by 48-72 hour follow-up call. |
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| Neck rash | Skin and subcutaneous tissue disorders | CTCAE v5 | Systematic Assessment | AE resolved by 48-72 hour follow-up call. |
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| Diarrhea, drowsiness, nausea | General disorders | CTCAE v5 | Systematic Assessment | AE resolved by 48-72 hour follow-up call. |
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Not provided
Not provided
| D024801 |
| Tauopathies |
| D019636 | Neurodegenerative Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
| D003072 | Cognition Disorders |
| Regression testing the interaction of temporal tau SUVR and amyloid SUVR in prediction of episodic memory. | Regression, Linear | Adjusted for age, sex, and years of education. | .604 | A priori threshold was two-sided 0.05. No adjustment for multiple comparisons. | Slope | -0.07 | Standard Error of the Mean | 0.13 | 2-Sided | 95 | -0.32 | 0.19 | Other | Null-hypothesis significance test |
| Regression testing the interaction of temporal tau SUVR and amyloid SUVR in the prediction of speed of processing. | Regression, Linear | Adjusted for age, sex, and years of education. | .154 | A priori threshold was two-sided 0.05. No adjustment for multiple comparisons. | Slope | 0.16 | Standard Error of the Mean | 0.11 | 2-Sided | 95 | -0.06 | 0.38 | Other | Null-hypothesis significance test |
| Regression testing the interaction of temporal tau SUVR and amyloid SUVR in prediction of reasoning. | Regression, Linear | Adjusted for age, sex, and years of education. | .428 | A priori threshold was two-sided 0.05. No adjustment for multiple comparisons. | Slope | 0.11 | Standard Error of the Mean | 0.13 | 2-Sided | 95 | -0.16 | 0.37 | Other | Null-hypothesis significance test |
| Regression testing the interaction of temporal tau SUVR and amyloid SUVR in prediction of working memory. | Regression, Linear | Adjusted for age, sex, and years of education. | .039 | A priori threshold was two-sided 0.05. No adjustment for multiple comparisons. | Slope | 0.27 | Standard Error of the Mean | 0.13 | 2-Sided | 95 | 0.01 | 0.53 | Other | Null-hypothesis significance test |
| Post hoc simple slopes test of the amyloid x tau interaction (Statistical Analysis #2) at 1SD below the mean for amyloid | sim_slopes (R interactions package) | .091 | A priori threshold was two-sided 0.017 after Bonferroni correction for multiple comparisons (3 post hoc tests). | Slope | -0.47 | Standard Error of the Mean | 0.27 | 2-Sided | Other | Null-hypothesis significance test |
| Post hoc simple slopes test of the amyloid x tau interaction (Statistical Analysis #2) at the mean for amyloid SUVR | sim_slopes (R interactions package) | .296 | A priori threshold was two-sided 0.017 after Bonferroni correction for multiple comparisons (3 post hoc tests). | Slope | -0.20 | Standard Error of the Mean | 0.19 | 2-Sided | Other | Null-hypothesis significance test |
| Post hoc simple slopes test of the amyloid x tau interaction (Statistical Analysis #2) at 1SD above the mean for amyloid SUVR | sim_slopes (R interactions package) | .695 | A priori threshold was two-sided 0.017 after Bonferroni correction for multiple comparisons (3 post hoc tests). | Slope | 0.07 | Standard Error of the Mean | 0.17 | 2-Sided | Other | Null-hypothesis significance test |
| Title | Measurements |
|---|---|
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| entorhinal SUVR |
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| parahippocampal SUVR |
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| fusiform SUVR |
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| Regression testing the relationship of age(quadratic) to inferior temporal SUVR. | Regression, Linear | No adjustments were made. | .905 | A priori threshold was two-sided 0.05. No adjustment for multiple comparisons. | Slope | -0.000005 | Standard Error of the Mean | 0.00004 | 2-Sided | 95 | -0.000009 | 0.00008 | Other | Null-hypothesis significance test |
| Regression testing the relationship of age(growth model) to inferior temporal SUVR. Growth modeling was performed using SPSS curve estimation. | Regression, Linear | No adjustments were made. | .006 | A priori threshold was two-sided 0.05. No adjustment for multiple comparisons. | Slope | 0.002 | Standard Error of the Mean | 0.001 | 2-Sided | Other | Null-hypothesis significance test |
| Regression testing the relationship of age(linear) to middle temporal gyrus SUVR. | Regression, Linear | No adjustments were made. | .018 | A priori threshold was two-sided 0.05. No adjustment for multiple comparisons. | Slope | 0.002 | Standard Error of the Mean | 0.001 | 2-Sided | 95 | 0.0003 | 0.003 | Other | Null-hypothesis significance test |
| Regression testing the relationship of age(quadratic) to middle temporal SUVR. | Regression, Linear | No adjustment for multiple comparisons. | .579 | A priori threshold was two-sided 0.05. No adjustment for multiple comparisons. | Slope | -0.00002 | Standard Error of the Mean | 0.00004 | 2-Sided | 95 | -0.0001 | 0.00006 | Other | Null-hypothesis significance test |
| Regression testing the relationship of age(growth model) to middle temporal SUVR. Growth modeling was performed using SPSS curve estimation. | Regression, Linear | No adjustments were made. | .008 | A priori threshold was two-sided 0.05. No adjustment for multiple comparisons. | Slope | 0.002 | Standard Error of the Mean | 0.001 | 2-Sided | Other | Null-hypothesis significance test |
| Regression testing the relationship of age to superior temporal SUVR. | Regression, Linear | No adjustments were made. | .897 | A priori threshold was two-sided 0.05. No adjustment for multiple comparisons. | Slope | 0.00006 | Standard Error of the Mean | 0.0004 | 2-Sided | 95 | -0.001 | 0.001 | Other | Null-hypothesis significance test |
| Regression testing the relationship of age(quadratic) to superior temporal SUVR. | Regression, Linear | No adjustments were made. | .539 | A priori threshold was two-sided 0.05. No adjustment for multiple comparisons. | Slope | -0.00002 | Standard Error of the Mean | 0.00003 | 2-Sided | 95 | -0.00007 | 0.00003 | Other | Null-hypothesis significance test |
| Regression testing the relationship of age(growth model) to superior temporal SUVR. Growth modeling was performed using SPSS curve estimation. | Regression, Linear | No adjustments were made. | .973 | A priori threshold was two-sided 0.05. No adjustment for multiple comparisons. | Slope | -0.00001 | Standard Error of the Mean | 0.0004 | 2-Sided | Other | Null-hypothesis significance test |
| Regression testing the relationship of age(linear) to entorhinal SUVR. | Regression, Linear | No adjustments were made. | .200 | A priori threshold was two-sided 0.05. No adjustment for multiple comparisons. | Slope | 0.001 | Standard Error of the Mean | 0.001 | 2-Sided | 95 | -0.001 | 0.003 | Other | Null-hypothesis significance test |
| Regression testing the relationship of age(quadratic) to entorhinal SUVR. | Regression, Linear | No adjustments were made. | .346 | A priori threshold was two-sided 0.05. No adjustment for multiple comparisons. | Slope | 0.00005 | Standard Error of the Mean | 0.00005 | 2-Sided | 95 | -0.00005 | 0.0001 | Other | Null-hypothesis significance test |
| Regression testing relationship of age(growth model) to entorhinal SUVR. Growth modeling was performed using SPSS curve estimation. | Regression, Linear | No adjustments were made. | .283 | A priori threshold was two-sided 0.05. No adjustment for multiple comparisons. | Slope | 0.001 | Standard Error of the Mean | 0.001 | 2-Sided | Other | Null-hypothesis significance test |
| Regression testing the relationship of age(linear) to parahippocampal SUVR. | Regression, Linear | No adjustments were made. | .011 | A priori threshold was two-sided 0.05. No adjustment for multiple comparisons. | Slope | 0.002 | Standard Error of the Mean | 0.001 | 2-Sided | 95 | 0.0004 | 0.003 | Other | Null-hypothesis significance test |
| Regression testing the relationship of age(quadratic) to parahippocampal SUVR. | Regression, Linear | No adjustments were made. | .536 | A priori threshold was two-sided 0.05. No adjustment for multiple comparisons. | Slope | 0.00002 | Standard Error of the Mean | 0.00003 | 2-Sided | 95 | -0.00004 | 0.00009 | Other | Null-hypothesis significance test |
| Regression testing the relationship of age(growth model) to parahippocampal SUVR. Growth modeling was performed using SPSS curve estimation. | Regression, Linear | No adjustments were made. | .013 | A priori threshold was two-sided 0.05. No adjustment for multiple comparisons. | Slope | 0.001 | Standard Error of the Mean | 0.001 | 2-Sided | Other | Null-hypothesis significance test |
| Regression testing the relationship of age(linear) to fusiform SUVR. | Regression, Linear | No adjustments were made. | <.001 | A priori threshold was two-sided 0.05. No adjustment for multiple comparisons. | Slope | 0.002 | Standard Error of the Mean | 0.0005 | 2-Sided | 95 | 0.001 | 0.003 | Other | Null-hypothesis significance test |
| Regression testing the relationship of age(quadratic) to fusiform SUVR. | Regression, Linear | No adjustments were made. | .692 | A priori threshold was two-sided 0.05. No adjustment for multiple comparisons. | Slope | 0.00001 | Standard Error of the Mean | 0.00003 | 2-Sided | 95 | -0.00004 | 0.00006 | Other | Null-hypothesis significance test |
| Regression testing the relationship of age(growth model) to fusiform SUVR. Growth modeling was performed using SPSS curve estimation. | Regression, Linear | No adjustments were made. | <.001 | A priori threshold was two-sided 0.05. No adjustment for multiple comparisons. | Slope | 0.001 | Standard Error of the Mean | 0.0004 | 2-Sided | Other | Null-hypothesis significance test |
| Title | Measurements |
|---|---|
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| parahippocampal thickness |
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| entorhinal thickness |
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| fusiform thickness |
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| Regression testing the relationship between temporal tau SUVR to middle temporal gyrus cortical thickness. | Regression, Linear | Adjusted for age, sex, and years of education | .636 | A priori threshold was two-sided 0.05. No adjustment for multiple comparisons. | Slope | 0.07 | Standard Error of the Mean | 0.16 | 2-Sided | 95 | -0.24 | 0.39 | Other | Null-hypothesis significance testing |
| Regression testing the relationship between temporal tau SUVR to superior temporal gyrus cortical thickness. | Regression, Linear | Adjusted for age, sex, and years of education. | .024 | A priori threshold was two-sided 0.05. No adjustment for multiple comparisons. | Slope | 0.38 | Standard Error of the Mean | 0.16 | 2-Sided | 95 | 0.05 | 0.70 | Other | Null-hypothesis significance testing |
| Regression testing the relationship between temporal tau SUVR to parahippocampal gyrus cortical thickness. | Regression, Linear | Adjusted for age, sex, and years of education. | .235 | A priori threshold was two-sided 0.05. No adjustment for multiple comparisons. | Slope | -0.27 | Standard Error of the Mean | 0.23 | 2-Sided | 95 | -0.73 | 0.18 | Other | Null-hypothesis significance testing |
| Regression testing the relationship between temporal tau SUVR to entorhinal gyrus cortical thickness. | Regression, Linear | Adjusted for age, sex, and years of education. | .639 | A priori threshold was two-sided 0.05. No adjustment for multiple comparisons. | Slope | 0.19 | Standard Error of the Mean | 0.41 | 2-Sided | 95 | -0.63 | 1.01 | Other | Null-hypothesis significance testing |
| Regression testing the relationship of temporal tau SUVR to fusiform gyrus cortical thickness. | Regression, Linear | Adjusted for age, sex, and years of education. | .252 | A priori threshold was two-sided 0.05. No adjustment for multiple comparisons. | Slope | 0.19 | Standard Error of the Mean | 0.16 | 2-Sided | 95 | -0.13 | 0.50 | Other | Null-hypothesis significance test |
| Title | Measurements |
|---|---|
|
| Regression testing the relationship of temporal tau SUVR to middle temporal gyrus activation (beta) on the semantic judgment fMRI task. | Regression, Linear | Adjusted for age, sex, and years of education. | .412 | A priori threshold was two-sided 0.05. No adjustment for multiple comparisons. | Slope | 0.24 | Standard Error of the Mean | 0.29 | 2-Sided | 95 | -0.34 | 0.81 | Other | Null-hypothesis significance test |
| Regression testing the relationship of temporal tau SUVR to precuneus gyrus activation (beta) on the semantic judgment fMRI task. | Regression, Linear | Adjusted for age, sex, and years of education. | .438 | A priori threshold was two-sided 0.05. No adjustment for multiple comparisons. | Slope | 0.31 | Standard Error of the Mean | 0.40 | 2-Sided | 95 | -0.48 | 1.09 | Other | Null-hypothesis significance test |