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December 2017

The Complexity of Subjective Cognitive Decline

Author Affiliations
  • 1Department of Neurology and Alzheimer Center, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, the Netherlands
  • 2Helen Wills Neuroscience Institute, University of California, Berkeley
JAMA Neurol. 2017;74(12):1400-1402. doi:10.1001/jamaneurol.2017.2224

Subjective cognitive decline (SCD), or self-perceived worsening of cognitive function in the absence of objective cognitive deficits, has attracted significant scientific attention for decades, because this phenomenon might reflect the earliest signs of an emerging neurodegenerative disease.1 Recently, investigators have struggled to standardize the measurement and definition of SCD, a complex problem because of its inherently subjective nature. Although these attempts have not resulted in consistent results, the presence of SCD is often associated with future objective cognitive decline and with conversion from normal cognition to mild cognitive impairment or even dementia.2 Furthermore, compared with individuals without SCD, those with SCD more often demonstrate brain abnormalities reminiscent of Alzheimer disease (AD), including pathophysiologic (increased cerebral β-amyloid [Aβ] deposition), neurodegenerative (greater atrophy and glucose hypometabolism in AD signature regions), and functional (disrupted functional connectivity) changes.3,4 These findings highlight the potential for SCD as an early marker of neurodegenerative conditions, because assessment of SCD might be more sensitive than traditional neuropsychological tests and is less expensive and invasive to measure than cerebrospinal fluid or neuroimaging biomarkers. However, SCD research is confronted with several unresolved challenges, primarily the variability in defining SCD across studies, the heterogeneity of factors related to SCD, and the limited knowledge of the neurobiological mechanisms underlying SCD.

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