Exploring the Accuracy of the Preclinical Alzheimer's Cognitive Composite (PACC) Relative to Amyloid Pathology for the Diagnosis of Alzheimer's Disease: A Systematic Review Protocol: What is the diagnostic accuracy and sensitivity of the Preclinical Alzheimer’s Cognitive Composite (PACC) for detecting preclinical Alzheimer’s Disease, compared to amyloid-PET imaging amongst people with elevated amyloid pathology?
Author
Jespersen, Sofie Imer
Term
4. term
Education
Publication year
2024
Submitted on
2024-05-30
Pages
53
Abstract
Background: Alzheimer’s disease can begin years before noticeable symptoms. A key early sign is the buildup of amyloid‑beta (Aβ) in the brain. As more people are affected worldwide, earlier detection is increasingly important. The Preclinical Alzheimer’s Cognitive Composite (PACC) is a set of neuropsychological tests designed to detect the very earliest changes in memory and thinking. Methods: We conducted a systematic review of 20 studies following PRISMA guidelines and the Joanna Briggs Institute diagnostic test accuracy protocol. PACC (the index test) was evaluated against a common reference: Aβ‑PET brain imaging. Across studies, we summarized sensitivity, specificity, and overall accuracy. Results: The evidence indicates that even low levels of Aβ on PET scans are associated with subtle cognitive differences detected by PACC, and higher Aβ levels relate to a faster rate of cognitive decline. Among PACC components, the Mini‑Mental State Examination (MMSE) and Digit Symbol Substitution Test (DSST) were especially sensitive to early change. Adding language measures such as the Category Fluency Test (CAT) may enhance overall sensitivity. Across versions, PACC detected changes in both early and later stages and helped distinguish preclinical Alzheimer’s, Mild Cognitive Impairment (MCI), and Alzheimer’s disease, supporting its usefulness in clinical trials and clinical care. Limitations: The included studies may be affected by selection and attrition bias, which can limit generalizability. Reliance on specific subtests may not capture all aspects of cognitive decline, and proposed additions require further validation. Conclusion: Elevated Aβ levels increase the risk of cognitive decline and possibly Alzheimer’s disease, supporting Aβ as an early biomarker. Further research is needed to clarify the causal relationship between Aβ pathology and cognition and to fully validate PACC for clinical use.
Baggrund: Alzheimers sygdom kan starte længe før tydelige symptomer viser sig. Et tidligt kendetegn er ophobning af amyloid‑beta (Aβ) i hjernen. Behovet for at opdage sygdommen tidligere vokser i takt med, at flere rammes. Preclinical Alzheimer’s Cognitive Composite (PACC) er et sæt neuropsykologiske prøver, der er udviklet til at opfange de allerførste ændringer i tænkning og hukommelse. Metode: Denne systematiske gennemgang omfatter 20 studier og følger PRISMA‑retningslinjerne samt Joanna Briggs Institute (JBI) protokol for diagnostisk testnøjagtighed. PACC (indeks‑testen) blev vurderet op imod en fælles reference: Aβ‑PET hjerneskanninger. På tværs af studierne blev sensitivitet, specificitet og nøjagtighed rapporteret. Resultater: Gennemgangen peger på, at selv lave niveauer af Aβ på PET‑skanning er forbundet med meget subtile kognitive ændringer målt med PACC, og at højere Aβ‑niveauer hænger sammen med hurtigere kognitivt fald. Blandt PACC‑delprøver var især Mini‑Mental State Examination (MMSE) og Digit Symbol Substitution Test (DSST) følsomme over for tidlige ændringer. Sprogtest som Category Fluency Test (CAT) kan muligvis øge PACC’s samlede følsomhed. På tværs af versioner af PACC fandt studierne, at PACC kan opfange ændringer både tidligt og senere i sygdomsforløbet og kan medvirke til at skelne mellem præklinisk Alzheimer, Mild Cognitive Impairment (MCI) og manifest Alzheimer. Dette gør PACC til et lovende, følsomt værktøj i både kliniske forsøg og klinisk praksis. Begrænsninger: De inkluderede studier kan være påvirket af udvælgelses‑ og frafaldsbias, hvilket kan begrænse generaliserbarheden. PACC’s afhængighed af bestemte delprøver kan betyde, at ikke alle aspekter af kognitivt fald fanges, og forslag om at tilføje yderligere delprøver kræver mere validering. Konklusion: Forhøjede Aβ‑niveauer øger risikoen for kognitivt fald og muligvis Alzheimer, hvilket understøtter Aβ som en tidlig biomarkør. Der er dog behov for mere evidens for at afklare den kausale sammenhæng mellem Aβ‑patologi og kognition og for at validere PACC fuldt ud til klinisk brug.
[This apstract has been rewritten with the help of AI based on the project's original abstract]
Keywords