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Studies suggest moving SNAP outside of Alzheimer’s framework

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Use cortical thickness as an early Alzheimer’s marker

The authors have provided a valuable contribution to an area that is receiving increasing attention. While they seem to ascribe small hippocampal volumes to variability in anatomic brain development, it may be that in older individuals, this is more appropriately ascribed to variability in non-Alzheimer’s disease pathologies, resistance to age-related neurodegeneration, or both – all of which should have slow rates of atrophy.

The authors recommended that the field shift from using hippocampal volume as a neurodegenerative measure to using a summary volumetric signature selective for Alzheimer’s disease. This seems justified, although not because hippocampal volume loss with increasing age represents individual variation in brain development. We recommend an Alzheimer’s disease signature (cortical) thickness measure because cortical thickness, unlike volume, is not dependent on head size. Thus, thickness does not need to be adjusted for variation in head size, which imparts a sex effect to all volume adjustments.

Clifford Jack, MD, is a professor of radiology at the Mayo Clinic in Rochester, Minn. He is an originator of the concept of suspected non-Alzheimer’s pathophysiology (SNAP) and also the National Institute on Aging–Alzheimer’s Association’s research criteria for preclinical Alzheimer’s disease. He is a consultant for Eli Lilly and owns stock in Johnson and Johnson. His commentary is adapted from his editorial accompanying the report from Dr. Gordon and his associates (JAMA Neurol. 2016 Aug 22. doi:10.1001/jamaneurol.2016.2843).


 

FROM JAMA NEUROLOGY

References

Overall, the two studies support SNAP as a “generally non-AD heterogeneous diagnosis that does in fact exhibit greater cognitive decline with age, even if subtle in the Mormino study, with an increased risk of MCI and dementia. If we look at the neuropathology of AD cases, we find similar additional pathologies, so maybe SNAP is that minus the AD piece,” said Dr. Caselli, who was not involved in either study.

The heterogeneity explains “our difficulties understanding” the nature of SNAP, Sylvia Villeneuve, PhD, said in an editorial to the Harvard study (JAMA Neurol. 2016 Aug 22. doi:10.1001/jamaneurol.2016.2842).

“Given that the cognitive and brain profile of most SNAP individuals are stable over time, some authors have suggested that neurodegeneration should not be a defining feature of SNAP. … Part of what we capture as SNAP represents a tail of the normal aging distribution,” said Dr. Villeneuve of McGill University in Montreal. “A better comprehension of the biomarkers used to characterize SNAP will be important, with an awareness of the limitations of bimodal markers” – the yes/no answers used for NIA and SNAP classification – “especially those with cutoffs that do not have a biological basis.”

Both studies were funded at least in part by the National Institutes of Health. Dr. Gordon reported research work with Avid Radiopharmaceuticals; Dr. Mormino had no industry disclosures. Other investigators in both projects reported ties to several companies, including Eli Lilly, Janssen, AbbVie, Roche, and Pfizer. Dr. Villeneuve had no disclosures.

aotto@frontlinemedcom.com

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