Predicting the Future: Researchers Eye New Early Predictor of Cognitive Decline

Evidence of Alzheimer’s Disease begins to appear in the brain well before clinical cognitive symptoms of the disease, which has led to the introduction of the term “preclinical Alzheimer’s Disease” to refer to individuals without cognitive impairment who aren’t showing any clinical symptoms of the disease. These individuals show signs of the amyloid plaques that characterize Alzheimer’s Disease. A number of factors, including many related to lifestyle, can influence how long individuals with preclinical Alzheimer’s remain cognitively stable before beginning to show the cognitive symptoms of the disease. However, the appearance of these amyloid plaques ultimately signals significantly increased risk of developing the dementia caused by Alzheimer’s Disease.

In light of this, many researchers have been searching for ways to identify predictors of cognitive deterioration in healthy older adults before this cognitive decline appears. Early identification of these predictors means that any effective treatment developed for Alzheimer’s Disease could be applied before the brain changes associated with the disease begin to produce noticeable cognitive changes in an individual. A new study in the journal Radiology has revealed a new method of using an MRI to predict cognitive deterioration in healthy older adults.

Earlier research on MRIs using this method (Arterial Spin Labeling or ASL) had compared differences between healthy control subjects and individuals with mild cognitive impairment (MCI), but whether this technique could detect early and subtle brain changes that could be used to predict the very early stages of cognitive decline had not been previously detected. In order to test whether early cognitive decline could be predicted using this ASL technique, healthy older adults received two MRIs using this method 18 months apart. At the time of the second scan, cognitive tests were used to classify these individuals as either having stable cognitive function or deteriorating cognitive function. This categorization of deteriorating cognitive function captures very subtle cognitive changes. Additionally, the scans of all of the healthy older adults in the study were compared to MRIs of individuals who had been clinically diagnosed with MCI. Overall, there were 213 participants in this study (a large number for expensive MRI studies), with an average age of 73. Of these, 75 were classified as having stable cognitive function, 73 with deteriorating cognitive function, and 65 had MCI.

When the first group of MRIs were compared, the researchers found differences between the individuals with stable cognitive function and those who later showed deteriorating cognitive function. Compared to individuals with stable cognitive function, individuals with deteriorating cognitive function showed decreased blood flow to the posterior cingulate cortex. Decreased blood flow in this region was also seen in the participants who were diagnosed with MCI. This ability to predict cognitive decline in advance of any clinical symptoms is an important diagnostic advance.

What can we learn from the specific region where the differences were observed? Many regions of the brain are involved in multiple cognitive processes, and more processes associated with certain brain regions are being constantly discovered, so it is not always clear what we can learn from observed changes in a particular region. However, the changes shown in the posterior cingulate cortex are consistent with findings from other studies related to differences between individuals in their cognitive reserve, a theory as to why individuals with certain predispositions, higher levels of education, and higher levels of social integration maintain normal cognitive function longer than other people even when comparing individuals with similar changes to their brains. In studies of cognitive reserve, the posterior cingulate cortex has been associated with compensation that allows individuals to maintain unimpaired cognitive performance for a period of time even as their brain is changing in patterns associated with eventual cognitive decline. This led the authors to suggest that at the start of the study, the individuals who later showed deteriorating cognitive function “were initially able to compensate for these [brain] changes and maintain normal cognitive status.”

This early prediction of cognitive deterioration has great potential for early interventions designed to counteract brain changes, such as drugs aimed at slowing or preventing brain changes, which could be delivered at a point when they could have the greatest impact on cognitive decline. The potential also exists for the development of behavioral interventions that could assist with strengthening the compensation processes in the brain that are allowing cognitive performance to be unimpaired despite detrimental changes occurring in the brain.


Xekardaki A, Rodriguez C, Montandon M-L, et al. Arterial spin labeling may contribute to the prediction of cognitive deterioration in healthy elderly individuals. Radiology. (2014). DOI:


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