The AHEAD 3‐45 Study: Design of a prevention trial for Alzheimer's disease

Rafii, Michael S.; Sperling, Reisa A.; Donohue, Michael C.; Zhou, Jin; Roberts, Claire; Irizarry, Michael C.; Dhadda, Shobha; Sethuraman, Gopalan; Kramer, Lynn D.; Swanson, Chad J.; Li, David; Krause, Stephen; Rissman, Robert A.; Walter, Sarah; Raman, Rema; Johnson, Keith A.; Aisen, Paul S.

doi:10.1002/alz.12748

Cited by 76 publications

(57 citation statements)

References 30 publications

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“…Amyloid PET scans with 11 C-Pittsburgh Compound B (or PiB) were obtained via previously described methods, and images were processed using the PET unified pipeline (PUP, https://github.com/ysu001/ PUP). 34,35 Briefly, dynamically acquired PET data were reconstructed into frames that underwent affine registration to correct for interframe motion.…”

Section: Positron Emission Tomography (Pet) Imagingmentioning

confidence: 99%

“…Amyloid PET is well correlated with AD neuropathology, 5–7 and is often used as the reference standard for brain amyloidosis 8,9 . Amyloid PET positivity is also used as an enrollment criterion for clinical trials, including trials in cognitively normal individuals that are designed to prevent or slow AD symptom onset 10,11 . Multiple studies have demonstrated that amyloid plaques, as measured by PET, accumulate consistently across individuals during preclinical AD (when individuals are amyloid positive but cognitively normal), enabling staging of preclinical AD with continuous measures of amyloid PET 12–17 …”

Section: Introductionmentioning

confidence: 99%

“…8,9 Amyloid PET positivity is also used as an enrollment criterion for clinical trials, including trials in cognitively normal individuals that are designed to prevent or slow AD symptom onset. 10,11 Multiple studies have demonstrated that amyloid plaques, as measured by PET, accumulate consistently across individuals during preclinical AD (when individuals are amyloid positive but cognitively normal), enabling staging of preclinical AD with continuous measures of amyloid PET. [12][13][14][15][16][17] Cerebrospinal fluid (CSF) and plasma amyloid beta (Aβ)42/Aβ40 have also been found to be accurate biomarkers of brain amyloidosis.…”

Section: Introductionmentioning

confidence: 99%

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Predicting continuous amyloid PET values with CSF and plasma Aβ42/Aβ40

Wisch

Gordon

Boerwinkle

et al. 2023

Alz & Dem Diag Ass & Dis Mo

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Introduction Continuous measures of amyloid burden as measured by positron emission tomography (PET) are being used increasingly to stage Alzheimer's disease (AD). This study examined whether cerebrospinal fluid (CSF) and plasma amyloid beta (Aβ)42/Aβ40 could predict continuous values for amyloid PET. Methods CSF Aβ42 and Aβ40 were measured with automated immunoassays. Plasma Aβ42 and Aβ40 were measured with an immunoprecipitation–mass spectrometry assay. Amyloid PET was performed with Pittsburgh compound B (PiB). The continuous relationships of CSF and plasma Aβ42/Aβ40 with amyloid PET burden were modeled. Results Most participants were cognitively normal (427 of 491 [87%]) and the mean age was 69.0 ± 8.8 years. CSF Aβ42/Aβ40 predicted amyloid PET burden until a relatively high level of amyloid accumulation (69.8 Centiloids), whereas plasma Aβ42/Aβ40 predicted amyloid PET burden until a lower level (33.4 Centiloids). Discussion CSF Aβ42/Aβ40 predicts the continuous level of amyloid plaque burden over a wider range than plasma Aβ42/Aβ40 and may be useful in AD staging. Highlights Cerebrospinal fluid (CSF) amyloid beta (Aβ)42/Aβ40 predicts continuous amyloid positron emission tomography (PET) values up to a relatively high burden. Plasma Aβ42/Aβ40 is a comparatively dichotomous measure of brain amyloidosis. Models can predict regional amyloid PET burden based on CSF Aβ42/Aβ40. CSF Aβ42/Aβ40 may be useful in staging AD.

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Section: Positron Emission Tomography (Pet) Imagingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Predicting continuous amyloid PET values with CSF and plasma Aβ42/Aβ40

Wisch

Gordon

Boerwinkle

et al. 2023

Alz & Dem Diag Ass & Dis Mo

View full text Add to dashboard Cite

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“… 4 , 16 The demand for biomarkers is likely to increase even more with the rising prospect of disease-modifying therapies for AD 17 - 21 and expansion of clinical trials evaluating investigational agents designed to prevent cognitive impairment in patients at high risk of developing dementia due to AD. 22 , 23 …”

Section: Ad Biomarkers In Clinical Practicementioning

confidence: 99%

“…4,16 The demand for biomarkers is likely to increase even more with the rising prospect of disease-modifying therapies for AD [17][18][19][20][21] and expansion of clinical trials evaluating investigational agents designed to prevent cognitive impairment in patients at high risk of developing dementia due to AD. 22,23 Established AD biomarkers include PET-neuroimaging and cerebrospinal fluid measures. However, PET-based measures are costly, are seldom covered by insurers, and require access to specialized neuroimaging infrastructure and expertise.…”

Section: Ad Biomarkers In Clinical Practicementioning

confidence: 99%

Alzheimer Disease Biomarkers in Clinical Practice: A Blood-Based Diagnostic Revolution

Paczynski

Day

2022

J Prim Care Community Health

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An estimated 6.1 million Americans live with cognitive impairment—a number that is expected to triple by 2050. Alzheimer disease (AD) is the most common cause of impairment. The development of blood-based biomarkers capable of detecting pathological changes of AD in living patients has the potential to revolutionize the diagnostic approach to cognitive impairment by enabling screening for AD using accessible, non-invasive measures of amyloid and tau neuropathology, with accuracy that increasingly approaches that seen with “gold standard” positron emission tomography and cerebrospinal fluid measures. Demand for biomarker testing is expected to intensify with the emergence of effective treatments for AD and related dementias. Clinicians in all fields must prepare to meet this demand. Primary care practitioners are well positioned to support dementia diagnosis and management, including the application and interpretation of biomarkers. This article reviews the current uses of AD biomarkers and the potential applications of emerging blood-based AD biomarkers in clinical practice.

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Dementia Prevention and Treatment

Reuben,

Kremen,

Maust

2024

JAMA Intern Med

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ImportanceDementia affects 10% of those 65 years or older and 35% of those 90 years or older, often with profound cognitive, behavioral, and functional consequences. As the baby boomers and subsequent generations age, effective preventive and treatment strategies will assume increasing importance.ObservationsPreventive measures are aimed at modifiable risk factors, many of which have been identified. To date, no randomized clinical trial data conclusively confirm that interventions of any kind can prevent dementia. Nevertheless, addressing risk factors may have other health benefits and should be considered. Alzheimer disease can be treated with cholinesterase inhibitors, memantine, and antiamyloid immunomodulators, with the last modestly slowing cognitive and functional decline in people with mild cognitive impairment or mild dementia due to Alzheimer disease. Cholinesterase inhibitors and memantine may benefit persons with other types of dementia, including dementia with Lewy bodies, Parkinson disease dementia, vascular dementia, and dementia due to traumatic brain injury. Behavioral and psychological symptoms of dementia are best treated with nonpharmacologic management, including identifying and mitigating the underlying causes and individually tailored behavioral approaches. Psychotropic medications have minimal evidence of efficacy for treating these symptoms and are associated with increased mortality and clinically meaningful risks of falls and cognitive decline. Several emerging prevention and treatment strategies hold promise to improve dementia care in the future.Conclusions and RelevanceAlthough current prevention and treatment approaches to dementia have been less than optimally successful, substantial investments in dementia research will undoubtedly provide new answers to reducing the burden of dementia worldwide.

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The AHEAD 3‐45 Study: Design of a prevention trial for Alzheimer's disease

Cited by 76 publications

References 30 publications

Predicting continuous amyloid PET values with CSF and plasma Aβ42/Aβ40

Predicting continuous amyloid PET values with CSF and plasma Aβ42/Aβ40

Alzheimer Disease Biomarkers in Clinical Practice: A Blood-Based Diagnostic Revolution

Dementia Prevention and Treatment

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