Early Predictors of Alzheimer’s Disease May Not Occur in a Specific Sequence

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by Kara Elam |

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A research article, titled, “Subtle Cognitive Decline and Biomarker Staging in Preclinical Alzheimer’s Disease” recently published in the Journal of Alzheimer’s Disease by a team of investigators from the University of California in San Diego (UCSD) School of Medicine and Veterans Affairs San Diego Healthcare System, indicates that the diagnostic picture of Alzheimer’s disease (AD) is not as black and white as the current scientific understanding of the disease’s progression dictates, and that early indicators or biomarkers (the measures used to perform a clinical assessment ie. blood pressure) of AD development are not anchored in a specific sequence.

About Alzheimer’s Disease

AD is a neurological disease that causes patients to have debilitating declines in brain function. It affects a patient’s memory, thinking, and cognitive reasoning skills. According to the CDC, as many as 5 million Americans are suffering from AD. The symptoms of the disease often first appear after age 60, and the risk for diagnosis increases substantially with age. It is projected that by 2050 the number of diagnosed cases will be in the range of 14 million.

Study Methods

In their study, researchers classified 570 cognitively normal participants in the Alzheimer’s Disease Neuroimaging Initiative according to the National Institute of Aging and the Alzheimer’s Association (NIA-AA) criteria, and then in a separate examination an assessment of the number of abnormal biological and cognitive markers associated with preclinical AD for each participant was conducted. They then examined only those participants who progressed to a diagnosis of mild cognitive impairment, which is an at-risk cognitive state of AD.

The primary study findings showed that neurodegeneration alone was 2.5 times more common than amyloid accumulation alone at baseline measurements.  Secondly, the team found that it was most common to show neurodegeneration as the first sign of early AD, and equally common to show amyloid accumulation or subtle cognitive decline as the first sign.

In a University press release on the study’s findings, Dr. Emily C. Edmonds, PhD, senior postdoctoral fellow in the Department of Psychiatry and lead study author stated, “Our current ability to identify early stages of AD is limited by the focus on amyloid accumulation and the expectation that biomarkers follow the same timeline for all individuals.”

Dr. Edmonds added that, “AD is complex in the sense that there may be different neurobiological pathways leading to expression of the disease. Our findings suggest that the number of abnormal biomarkers and cognitive markers an individual possesses, without regard to the temporal sequence, is most predictive of future decline.”

In her opinion Dr. Edmonds thinks that the findings highlight the need to improve identification of persons at risk for AD through the use of multiple, diverse assessment tools, explaining that, “At present, it is much more common for assessment of cognition to be based on insensitive screening measures or reports of cognitive problems by patients or their family members. These blunt screening tools can be very unreliable, which might explain why cognitive decline has traditionally been viewed as occurring later in the disease process. The integration of sensitive neuropsychological measures with assessment of biomarkers of AD can enhance our ability to more accurately identify individuals who are at risk for future progression to AD.”