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.

INTRODUCTION Our goal was to develop cut-points for amyloid PET, tau PET, FDG PET, and MRI cortical thickness. METHODS We examined five methods for determining cut-points. RESULTS The reliable worsening method produced a cut-point only for amyloid PET. The specificity, sensitivity, and accuracy of clinically impaired versus young clinically normal (CN) methods labeled the most people positive and all gave similar cut-points for tau PET, FDG PET and cortical thickness. Cut-points defined using the accuracy of clinically impaired versus age-matched CN method labeled fewer people positive. DISCUSSION In the future, we will employ a single cut-point for amyloid PET (SUVR 1.42, centiloid 19) based on the reliable worsening cut-point method. We will base lenient cut-points for tau PET, FDG PET and cortical thickness on the accuracy of clinically impaired vs young CN method and base conservative cut-points on the accuracy of clinically impaired vs age-matched CN method.

With the aging of the population, the burden of Alzheimer’s disease (AD) is rapidly expanding. More than 5 million people in the US alone are affected with AD and this number is expected to triple by 2050. While men may have a higher risk of mild cognitive impairment (MCI), an intermediate stage between normal aging and dementia, women are disproportionally affected with AD. One explanation is that men may die of competing causes of death earlier in life, so that only the most resilient men may survive to older ages. However, many other factors should also be considered to explain the sex differences. In this review, we discuss the differences observed in men versus women in the incidence and prevalence of MCI and AD, in the structure and function of the brain, and in the sex-specific and gender-specific risk and protective factors for AD. In medical research, sex refers to biological differences such as chromosomal differences (eg, XX versus XY chromosomes), gonadal differences, or hormonal differences. In contrast, gender refers to psychosocial and cultural differences between men and women (eg, access to education and occupation). Both factors play an important role in the development and progression of diseases, including AD. Understanding both sex- and gender-specific risk and protective factors for AD is critical for developing individualized interventions for the prevention and treatment of AD.

Plasma pTau181 may have utility as a biomarker of AD pathophysiology and as a noninvasive screener for elevated brain Aβ.