In the JournalsPerspective

Combined testing may detect Alzheimer's disease earlier than standard methods

Jeremy A. Elman

Initiating Alzheimer’s disease treatment before amyloid-beta levels become pathological provides patients with significant benefit, according to study findings published in Biological Psychiatry. Researchers noted that noninvasive, low-cost cognitive measures may help determine patients at risk for progressing to amyloid-beta positivity.

“There have been massive advances in Alzheimer’s disease biomarkers that have been critical to improving our understanding and study of the disease,” Jeremy A. Elman, PhD, of the department of psychiatry at University of California, San Diego, told Healio Psychiatry. “However, this study serves as an important reminder that cognitive testing remains a powerful tool in our toolkit, even during the earliest stages of the disease. These results also contribute to emerging evidence that even very low levels of pathology are clinically relevant and should be monitored closely.”

Elman and colleagues noted that although amyloid-beta levels become abnormal well before the appearance of severe cognitive impairments, mounting research has suggested that subtle cognitive changes may begin before amyloid-beta surpasses the threshold for abnormality. To determine whether baseline cognitive performance predicted progression from normal to abnormal levels, the researchers examined the association of baseline cognitive composites called the Preclinical Alzheimer Cognitive Composite and the Alzheimer’s Disease Neuroimaging Initiative (ADNI) with progression to amyloid-beta positivity in 292 nondemented, amyloid-beta-negative participants. In additional analyses, they examined the effects of subthreshold pathology using continuous cerebrospinal fluid biomarker levels.

During follow up, 40 participants progressed to amyloid-beta positivity. The researchers reported a significant association between poorer baseline performance on both cognitive measures and increased odds of progression. Further, more abnormal levels of subthreshold amyloid-beta and baseline cerebrospinal fluid phosphorylated tau were associated with increased odds of progression to amyloid-beta positivity. Participant performance on baseline ADNI memory factory composite predicted progression even when the researchers controlled for baseline biomarker levels and apolipoprotein E genotype. Survival analyses revealed similar results; namely, after controlling for baseline biomarker levels, baseline Preclinical Alzheimer Cognitive Composite still significantly predicted progression time to amyloid-beta positivity.

“Measures of amyloid and tau pathology are necessary to diagnose Alzheimer’s disease, but obtaining these measures can require expensive and/or invasive procedures,” Elman said. “A comprehensive battery of cognitive tests may be a relatively time- and cost-effective first-line screening tool to determine which individuals should undergo further assessment. There is often a focus on finding the single best cognitive test to use in detecting Alzheimer’s disease, but in line with work from our group and others, we think that the increased sensitivity gained from combining multiple tests is well worth the time and effort needed to collect them.” – by Joe Gramigna

Disclosures: The authors report no relevant financial disclosures.

Jeremy A. Elman

Initiating Alzheimer’s disease treatment before amyloid-beta levels become pathological provides patients with significant benefit, according to study findings published in Biological Psychiatry. Researchers noted that noninvasive, low-cost cognitive measures may help determine patients at risk for progressing to amyloid-beta positivity.

“There have been massive advances in Alzheimer’s disease biomarkers that have been critical to improving our understanding and study of the disease,” Jeremy A. Elman, PhD, of the department of psychiatry at University of California, San Diego, told Healio Psychiatry. “However, this study serves as an important reminder that cognitive testing remains a powerful tool in our toolkit, even during the earliest stages of the disease. These results also contribute to emerging evidence that even very low levels of pathology are clinically relevant and should be monitored closely.”

Elman and colleagues noted that although amyloid-beta levels become abnormal well before the appearance of severe cognitive impairments, mounting research has suggested that subtle cognitive changes may begin before amyloid-beta surpasses the threshold for abnormality. To determine whether baseline cognitive performance predicted progression from normal to abnormal levels, the researchers examined the association of baseline cognitive composites called the Preclinical Alzheimer Cognitive Composite and the Alzheimer’s Disease Neuroimaging Initiative (ADNI) with progression to amyloid-beta positivity in 292 nondemented, amyloid-beta-negative participants. In additional analyses, they examined the effects of subthreshold pathology using continuous cerebrospinal fluid biomarker levels.

During follow up, 40 participants progressed to amyloid-beta positivity. The researchers reported a significant association between poorer baseline performance on both cognitive measures and increased odds of progression. Further, more abnormal levels of subthreshold amyloid-beta and baseline cerebrospinal fluid phosphorylated tau were associated with increased odds of progression to amyloid-beta positivity. Participant performance on baseline ADNI memory factory composite predicted progression even when the researchers controlled for baseline biomarker levels and apolipoprotein E genotype. Survival analyses revealed similar results; namely, after controlling for baseline biomarker levels, baseline Preclinical Alzheimer Cognitive Composite still significantly predicted progression time to amyloid-beta positivity.

“Measures of amyloid and tau pathology are necessary to diagnose Alzheimer’s disease, but obtaining these measures can require expensive and/or invasive procedures,” Elman said. “A comprehensive battery of cognitive tests may be a relatively time- and cost-effective first-line screening tool to determine which individuals should undergo further assessment. There is often a focus on finding the single best cognitive test to use in detecting Alzheimer’s disease, but in line with work from our group and others, we think that the increased sensitivity gained from combining multiple tests is well worth the time and effort needed to collect them.” – by Joe Gramigna

Disclosures: The authors report no relevant financial disclosures.

    Perspective

    Due to advances in biomarker research, we know that biological changes are occurring in the brains of people with Alzheimer's 10 to 20 years before cognitive symptoms become noticeable. Moving forward, it will be important to improve upon our ability to detect even subtle changes in cognition at the earliest possible time point, as early detection and diagnosis will be crucial for effective treatment and prevention. In addition, to support clinical care, we must continue to refine these prediction models to better determine who is at risk and promote earlier diagnosis, clinical trial enrollment and more effective treatment plans.

    Studies like this wouldn't be possible without data sharing through the ADNI, which is made possible through a public private partnership including the Alzheimer’s Association. The more we share and mine data, the more accurately we can model the trajectory of Alzheimer's disease, define detection strategies and develop treatments. 

    • Rebecca Edelmayer, PhD
    • Director of scientific engagement
      Alzheimer's Association

    Disclosures: Edelmayer is employed by the Alzheimer's Association.