Magazine article Clinical Psychiatry News

Studies Suggest Moving SNAP outside of Alzheimer's

Magazine article Clinical Psychiatry News

Studies Suggest Moving SNAP outside of Alzheimer's

Article excerpt


Two studies from JAMA Neurology raise doubts about whether suspected non-Alzheimer's pathophysiology--a brain biomarker construct suspected by some to be an Alzheimer's disease precursor--truly belongs on the Alzheimer's spectrum.

A team from Washington University in St. Louis concluded that neurodegeneration in isolation without beta-amyloid deposition the definition of suspected non-Alzheimer's pathophysiology (SNAP)--"often represents comorbid influences rather than emerging" Alzheimer's disease (JAMA Neurol. 2016 Aug 22. doi: 10.1001 /jamaneurol.2016.2642).

A team from Harvard Medical School in Boston came to a similar conclusion, finding that patterns of neurodegeneration in brain regions vulnerable to Alzheimer's disease (AD) "are not specific to AD processes among [clinically normal] individuals. Instead, multiple causes likely contribute to the biomarker construct of SNAP" (JAMA Neurol. 2016 Aug 22. doi: 10.1001/jamaneurol.2016.2237).

The relationship between SNAP and AD is, for now, mostly of concern to researchers. SNAP originally was linked to cerebral vascular disease and other age-related problems, but since it was proposed a few years ago as an addition to the National Institute on Aging (NIA)--Alzheimer's Association's research criteria for preclinical AD, it's been unclear how--or if--it really fits. The two research groups tackled the issue.

Patients in stage 1 of the NIA scheme have biomarker evidence of amyloid deposition without neuro-degeneration (ND); stage 2 patients have both. Stage 3 adds cognitive decline to the amyloid and ND signs. SNAP captures cognitively normal patients with ND but no evidence of amyloid deposition.

Over a period of 9 years, the St. Louis team split 174 cognitively normal adults--about equal numbers of men and women with an average age of 66--into the four groups at baseline, plus a fifth: no evidence of ND or amyloid. Amyloid deposition was assessed by positron emission tomography, and ND was assessed by both hippocampal volume loss on MRI and cerebrospinal fluid levels of the AD-linked tau protein.

Amyloid accumulation and hippocampal loss were greater in the later NIA stages than in either SNAP or biomarker-free subjects. Among the 34 SNAP patients (20%), only about 5 went on to deposit amyloid.

"The rates of [amyloid] accumulation and loss of hippocampal volume in individuals with SNAP were indistinguishable from those without any pathologic features at baseline.... SNAP appears most likely to capture inherent individual variability in brain structure or to represent comorbid pathologic features rather than early emerging AD. Low hippocampal volumes or elevated levels of [tau protein] in isolation may not accurately represent ongoing neurodegenerative processes," said investigators led by Brian Gordon, PhD.

Meanwhile, in the Harvard study, only "a small subset" of the 64 SNAP patients went on to rapid cognitive decline. SNAP seems to be "heterogeneous, and further biomarker refinement will be necessary to characterize this group," said investigators led by Elizabeth Mormino, PhD.

The Harvard team split 247 clinically normal individuals--a bit more women than men this time, with an average age of 74 years--into NIA categories, SNAP, and patients with no ND or amyloid biomarkers. Hippocampal volume was again assessed by MRI; positron emission tomography scans were used to assess amyloid deposition, but also regional brain tau protein levels and other pathologies, and there was serial cognitive testing. The study started in 2010 and is ongoing, with subjects evaluated yearly. …

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