Neurodegeneration does not necessarily signal cognitive decline
medwireNews: Neurodegeneration on its own does not significantly increase an individual’s risk of developing Alzheimer’s disease (AD), indicate findings from a two-marker imaging study.
The study of 573 cognitively healthy individuals aged an average of 73.1 years showed that increased β-amyloid (Aβ) deposition was the deciding factor in hastening cognitive decline and Alzheimer’s pathology progression with neurodegeneration having a compounding effect.
In the absence of Aβ deposition, elevated neurodegeneration was associated with no greater risk of cognitive decline or disease progression than having normal levels of both biomarkers.
The findings, published in The Lancet Neurology, give support to the term suspected non-Alzheimer’s disease pathology (SNAP) for patients with neurodegeneration alone being “a separate pathophysiological disorder or group of disorders with cognitive and clinical trajectories that are different from the Alzheimer’s disease pathway”, say Victor Villemagne (University of Melbourne, Heidelberg, Victoria, Australia) and co-researchers.
Among the participants, who were enrolled in the Australian Imaging, Biomarker and Lifestyle (AIBL) study, just over half (54%) were negative for both Aβ deposition and neurodegeneration (A–N–), 22% were negative for Aβ deposition but positive for neurodegeneration (A–N+; SNAP), 15% were positive for Aβ deposition but not neurodegeneration (A+N–) and 9% were positive for Aβ deposition and neurodegeneration (A+N+).
At baseline, patients positive for neurodegeneration, including those in the SNAP group, had significantly smaller hippocampal volumes as a result compared with the other groups. But only those with accompanying Aβ deposition showed significant hippocampal atrophy over time, decreasing by 0.05 cm3 per year versus 0.01 cm3 per year in controls. Volumes remained largely stable in the SNAP group, with a decline of just 0.0002 cm3 per year.
Patients with SNAP also did not show significant cognitive decline over time similar to elderly adults without elevated biomarkers, despite the SNAP group have lower average baseline cognitive scores, at 0.20 standard deviation, on the AIBL-Preclinical AD Cognitive Composite (PACC).
By contrast, patients positive for Aβ deposition without neurodegeneration scored significantly worse over time on the AIBL-PACC (difference of 0.083 SD per year), Mini-Mental State Examination (0.097 SD per year) and California Verbal Learning Test-II Long Delayed Free Recall (CVLT-II LDFR; 0.068 SD per year). Those positive for Aβ deposition and neurodegeneration scored similarly worse on these measures and measures of verbal episodic memory, executive function and the Clinical Dementia Rating Sum of Boxes.
Over the follow-up, 24% of A+N+ patients and 16% of A+N– patients progressed to amnestic mild cognitive impairment or AD, compared with just 9% of SNAP patients.
Commenting on the findings in a related editorial, Gérard Bischof (University Hospital Cologne, Germany) says there are “[t]wo important inferences of high clinical relevance” that can be drawn from the findings.
“First, this study underscores the clinical usefulness of in-vivo imaging of amyloid deposition and its high prognostic value in assessing the potential cognitive fate of the patient, and second, it brings hope to patients who are amyloid negative but have decreased hippocampus volume, which does not seem to confer an additional risk of cognitive decline”, he writes.
By Lucy Piper
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