There is increasing evidence that subjective cognitive decline (SCD) in individuals with unimpaired performance on cognitive tests may represent the first symptomatic manifestation of Alzheimer’s disease (AD). The research on SCD in early AD, however, is limited by the absence of common standards. The working group of the Subjective Cognitive Decline Initiative (SCD-I) addressed this deficiency by reaching consensus on terminology and on a conceptual framework for research on SCD in AD. In this publication, research criteria for SCD in pre-mild cognitive impairment (MCI) are presented. In addition, a list of core features proposed for reporting in SCD studies is provided, which will enable comparability of research across different settings. Finally, a set of features is presented, which in accordance with current knowledge, increases the likelihood of the presence of preclinical AD in individuals with SCD. This list is referred to as SCD plus.

EN-US" style="color: black;">In this seminar the main developments in the field of Alzheimer’s Disease (AD) are highlighted. Most recent data estimate a doubling of dementia prevalence in Europe by 2050. When prevalence estimates of AD are made on a biological, rather than a clinical definition of AD, the prevalence of biologically defined AD is three times higher than that of clinically defined AD. The biological definition based on biomarkers of Aβ and tau has been suggested for research and may enter the clinic in due course. The earliest, cellular, phase of AD includes alterations in neurons, microglia and astroglia. Neuro-inflammation,¹ alterations in the vessels, aging, dysfunction of the glymphatic system act upstream or in parallel to accumulating Aβ in this cellular disease landscape.  Aβ induces the spreading of tau pathology, which is associated with the appearance of necroptosis markers in neurons displaying granulo-vacuolar degeneration. Risk of AD depends for 60-80% on heritable factors. Causative genes include PSEN 1, PSEN2, APP and Sorl1. Risk genes include one or two alleles of APOE4. GWAS studies have identified another 40 risk genes. Protective genes include APOE2, and mutations in the PLCG2 , KLOTHO and the Icelandic APP A673T genes.

Next to the established CSF markers, novel biomarkers include plasma assays for Aβ and p-tau which show great promise for clinical use. Amyloid PET is now making its way into the clinical arena, while tau-PET is established in research.  Multidomain lifestyle-based prevention trials suggest cognitive benefits in subpopulations of participants with increased risk of dementia. Lifestyle factors do not directly impact AD pathology, but can still contribute to a positive outcome in individuals with AD. Promising pharmacological treatments are poised at advanced stages of testing in clinical trials and include anti-abeta, anti tau, anti-inflammatory strategies.