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Feb 27, 2013

In Treating Cognitive Decline, Timing Is Crucial

  • Scientists working at the Mayo Clinic say they have modeled the temporal accumulation of Beta amyloid plaques in the brain linked to decline in memory and thinking abilities. The study appeared in the online edition of Neurology on February 27th.

    Knowledge of the temporal pattern of plaque deposition, could, the Mayo scientists said, identify the optimal time during the course of its accumulation that therapeutic intervention might prove most effective.

    In their study, plaque accumulation over time was assessed using serial amyloid position emission tomography (PET) imaging to test individuals, aged 70–92, who were enrolled in either the Mayo Clinic Study of Aging or the Mayo Alzheimer’s Disease Research Center.

    Study participants included 205 individuals classified as cognitively normal and 55 as cognitively impaired (47 mild cognitive impairment and 8 Alzheimer’s dementia). All underwent two or more serial amyloid PET. The investigators measured baseline amyloid PET relative standardized uptake values (SUVR) and, for each participant, estimated a slope representing each patient’s annual amyloid accumulation rate.

    The data implied a roughly 15-year interval from an SUVR of 1.5 to 2.5. This period during which the slope of the amyloid SUVR vs. time curve is greatest and roughly linear represents, they said, a large therapeutic window for secondary preventative interventions. The study found that the rate of buildup accelerates initially, and then slows before plateauing at high levels. The rate of plaque accumulation was highest in those with mid-range levels at the start of the study. Those with low levels or high levels of the plaques as the study began had lower rates of plaque buildup.

    The authors said their data implied that therapeutic interventions designed to reduce the rate of new amyloid deposition (noting the distinction from removing previously deposited amyloid) may be less effective in patients who have already reached plateau levels of amyloid deposition.

    Lead study author Clifford Jack, Jr., M.D., a Mayo clinic radiologist and the Alexander Family Professor of Alzheimer’s Disease Research at Mayo, said that the study supports the role that plaque formation in the brain plays in a decline in memory and thinking abilities, and takes about 15 years to build up and then plateau.

    “Our results suggest that there is a long treatment window where medications may be able to help slow buildup of the amyloid plaques that are linked to cognitive decline,” he noted. “On the other hand, trying to treat the plaque buildup after the amyloid plaque load has plateaued may not do much good.”

    Interestingly, the study also found that the rate of buildup of plaques was more closely tied to the total amount of amyloid plaques in the brain than other risk factors, including level of cognitive impairment, age, and the presence of the APOE gene, a gene linked to Alzheimer's disease.


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