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Subtle cognitive difficulties predict future neurodegeneration

January 09, 2020

By Will Boggs MD

NEW YORK (Reuters Health) - Objectively defined subtle cognitive difficulties appear to be associated with future amyloid accumulation and neurodegeneration, according to findings from the Alzheimer's Disease Neuroimaging Initiative (ADNI).

"The objectively defined subtle cognitive difficulties (Obj-SCD) criteria have yet to be implemented in a clinical setting, as this approach needs to be validated in participants with greater diversity of race/ethnicity, education levels, and health comorbidities," Dr. Mark W. Bondi and Dr. Kelsey R. Thomas of the University of California, San Diego, in La Jolla, told Reuters Health in a joint email.

"As they stand, however," they said, "the current results suggest that this approach using sensitive neuropsychological measures can provide meaningful prognostic information about future risk for Alzheimer's disease progression in those who do not yet have frank cognitive impairment consistent with mild cognitive impairment (MCI)."

Dr. Bondi and colleagues previously found that Obj-SCD were significantly associated with CSF Alzheimer's disease markers and predicted faster progression to MCI/dementia, when compared with cognitively normal individuals.

In the current study, they aimed to determine whether Obj-SCD appeared after amyloid neurodegeneration or, instead, predicted future amyloid accumulation and medial temporal lobe neurodegeneration.

The study included 305 cognitively normal individuals, 153 with Obj-SCD, and 289 with MCI.

At 48 months, 46.0% of the Obj-SCD group had been classified as MCI, compared to only 16.9% of the cognitively normal group.

Baseline levels of amyloid deposition did not differ significantly between the groups.

The increase in amyloid accumulation was more than twice as fast in the Obj-SCD group as in the cognitively normal group, whereas the rate in the MCI group did not differ significantly from the cognitively normal or Obj-SCD groups, the researchers report in Neurology.

Compared with the cognitively normal group, those with Obj-SCD and MCI had faster entorhinal-cortex thinning. The Obj-SCD group had slower rates of entorhinal-cortical thinning than did the MCI group.

The rate of hippocampal volume loss was faster among participants with MCI than among cognitively normal individuals, but this rate did not differ significantly between Obj-SCD participants and the other groups.

"The current study suggests that sensitive neuropsychological measures may be used to identify subtle cognitive difficulties and inefficiencies earlier in the disease process than previously thought feasible, during a period when, on average, amyloid is still accumulating at a more rapid rate and neurodegenerative changes are just beginning," Dr. Thomas and Dr. Bondi said.

"While the emergence of biomarkers of Alzheimer's disease (AD) has revolutionized research and our understanding of how the disease progresses, many of these biomarkers continue to be expensive, inaccessible for clinical use, or not available to those with certain medical conditions," they said. "A method of identifying individuals at risk for progression to AD using neuropsychological measures has the potential to improve early detection in those who may otherwise not be eligible for more expensive or invasive screening."

SOURCE: Neurology, online December 20, 2019.

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