News

A third of older adults may have biomarkers of preclinical Alzheimer’s

View on the News

Study supports criteria, but data are confusing

The study by Dr. Stephanie Vos and her colleagues supports the emerging understanding of preclinical staging of Alzheimer’s disease – a concept useful not only for identifying at-risk populations, but for stratifying patient groups in therapeutic trials, Dr. Ronald Petersen wrote in an accompanying editorial (Lancet Neurol. 2013 Sept. 4 [doi:10.1016/S1474-4422(13)70217-5]).

However, he noted, the authors’ data on disease progression is "a bit more difficult to interpret than the frequencies of participants in each stage of preclinical AD."

For example, he noted, the researchers "chose to label the category for the next phase of progression in the AD spectrum as symptomatic AD rather than the more conventional mild cognitive impairment due to AD, amnestic MCI, or prodromal AD. The reason for this terminology is unclear and is likely to add to confusion in the published work."

Dr. Vos and her colleagues’ dichotomization of subjects as normal or abnormal at baseline made no allowance for a symptomatic predementia, he noted – a position that "is inconsistent with the published work from other groups in the specialty." This elimination of mild cognitive impairment from the preclinical staging equation complicates any comparison to prior work.

"The investigators [also] contend that the Clinical Dementia Rating scale is sufficient to verify symptomatic AD irrespective of cognitive test results. The CDR is a staging and not a diagnostic instrument; thus, why all normal participants in this study who progressed were classified as having a diagnosis of symptomatic AD is not clear."

"Notwithstanding these concerns, this study is an important contribution to the published work and supports the NIA-AA criteria for preclinical AD," Dr. Petersen concluded. "Importantly, despite the differences in methodology and types of participants, the findings from this study, which used CSF, and the Mayo Clinic Study of Aging, which used neuroimaging, converge convincingly."

Dr. Ronald Petersen is director of the Mayo Clinic Alzheimer’s Disease Research Center in Rochester, Minn. He had no financial disclosures.


 

FROM THE LANCET NEUROLOGY

After adjustment for multiple covariates, subjects with baseline stage 1 disease were not significantly more likely to progress than was the normal group. However, those in baseline stages 2 and 3 were more likely to progress (hazard ratio 14.3 and 33.8, respectively). Those in the SNAP group were not at a significantly increased risk of progression, compared with the normal group.

After adjustment for covariates, the risk of death was significantly greater in those with baseline preclinical disease (HR 6.2). When the stages were individually assessed, the risk increased as the stages did: HR 3.7 for stage 1, 6.0 for stage 2, and 31.5 for stage 3. Those in the SNAP group were 5.2 times more likely to die by the end of follow-up than were those in the normal group.

Nine subjects with baseline preclinical disease who died received a postpartum autopsy diagnosis. Of these, one had low neuropathological changes consistent with Alzheimer’s and the rest had intermediate-high changes.

Four subjects in the SNAP group who died underwent autopsy. Of these, three had low-level neuropathological changes, including vascular comorbidities. All had a neuritic plaque score of 0. This finding suggests that the cognitive changes were linked to other disorders, the authors said.

Dr. Vos received support from the Center for Translational Molecular Medicine, project LeARN and the EU/EFPIA Innovative Medicines Initiative Joint Undertaking, and Internationale Stichting Alzheimer Onderzoek. Several coauthors were investigators for industry-sponsored studies testing anti-dementia drugs or had ties with pharmaceutical companies developing Alzheimer’s diagnostic tests or therapies.

msullivan@frontlinemedcom.com

On Twitter @Alz_Gal

Pages

Recommended Reading

Higher glucose linked to increased dementia risk
MDedge Psychiatry
New drug matched donepezil’s efficacy in mild to moderate Alzheimer’s
MDedge Psychiatry
Alzheimer’s biomarkers have limited use in diagnosing frontotemporal dementia
MDedge Psychiatry
Labor induction, augmentation may be tied to autism risk
MDedge Psychiatry
Studies speak volumes about brain changes and cognition in women
MDedge Psychiatry
For atypical dementia, temporoparietal cortical thickness beats hippocampal volume
MDedge Psychiatry
Caregiver support program decreases dementia emergency visits
MDedge Psychiatry
Investigational treatments for cognitive impairment in schizophrenia
MDedge Psychiatry
Diagnosing Alzheimer’s: The eyes may have it
MDedge Psychiatry
Redesign needed for Alzheimer’s screening programs
MDedge Psychiatry