Evolving Evidence for the Value of Neuroimaging Methods and Biological Markers in Subjects Categorized with Subjective Cognitive Decline

Simone Lista, Jose L. Molinuevo, Enrica Cavedo, Lorena Rami, Philippe Amouyel, Stefan J. Teipel, Francesco Garaci, Nicola Toschi, Marie Odile Habert, Kaj Blennow, Henrik Zetterberg, Sid E. O'Bryant, Leigh Johnson, Samantha Galluzzi, Arun L.W. Bokde, Karl Broich, Karl Herholz, Hovagim Bakardjian, Bruno Dubois, Frank JessenMaria C. Carrillo, Paul S. Aisen, Harald Hampel

Research output: Contribution to journalReview articlepeer-review

29 Scopus citations


There is evolving evidence that individuals categorized with subjective cognitive decline (SCD) are potentially at higher risk for developing objective and progressive cognitive impairment compared to cognitively healthy individuals without apparent subjective complaints. Interestingly, SCD, during advancing preclinical Alzheimer's disease (AD), may denote very early, subtle cognitive decline that cannot be identified using established standardized tests of cognitive performance. The substantial heterogeneity of existing SCD-related research data has led the Subjective Cognitive Decline Initiative (SCD-I) to accomplish an international consensus on the definition of a conceptual research framework on SCD in preclinical AD. In the area of biological markers, the cerebrospinal fluid signature of AD has been reported to be more prevalent in subjects with SCD compared to healthy controls; moreover, there is a pronounced atrophy, as demonstrated by magnetic resonance imaging, and an increased hypometabolism, as revealed by positron emission tomography, in characteristic brain regions affected by AD. In addition, SCD individuals carrying an apolipoprotein β4 allele are more likely to display AD-phenotypic alterations. The urgent requirement to detect and diagnose AD as early as possible has led to the critical examination of the diagnostic power of biological markers, neurophysiology, and neuroimaging methods for AD-related risk and clinical progression in individuals defined with SCD. Observational studies on the predictive value of SCD for developing AD may potentially be of practical value, and an evidence-based, validated, qualified, and fully operationalized concept may inform clinical diagnostic practice and guide earlier designs in future therapy trials.

Original languageEnglish
Pages (from-to)S171-S191
JournalJournal of Alzheimer's Disease
Issue numberS1
StatePublished - 24 Sep 2015


  • Alzheimer's disease
  • biological markers
  • blood-based biomarkers
  • cerebrospinal fluid biomarkers
  • clinical trials
  • functional MRI markers
  • molecular imaging markers
  • preclinical Alzheimer's disease
  • structural MRI markers
  • subjective cognitive decline


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