Neuropsychological assessment in preclinical and prodromal Alzheimer disease: a global perspective

Alzheimer disease (AD), the most prevalent form of dementia, refers to a syndrome in which cognitive ability declines to such a degree that functioning in daily and/or social activities is compromised. In 2015, there were approximately 47 million people living with dementia globally, a figure expected to rise to 131 million by 2050. By as soon as 2030, the worldwide prevalence of dementia is estimated to reach 75 million with the majority of cases concentrated in low- and middle-income countries (LMiCs) [1-3]. Ageing worldwide populations beget greater numbers of older individuals living with chronic health conditions, such as dementia, which might pose significant social and economic challenges, most notably, for LMiCs [4]. In high income countries (HiCs), the focus of dementia detection is evolving to further encompass earlier stages of disease with the view to promote future approaches in secondary prevention. It is now accepted that AD-related pathology, such as amyloid and/or tau deposition, occurs decades before the onset of dementia symptoms [5]. The earliest sites of amyloidosis and tauopathy are the medial temporal lobe (MTL) structures, namely the hippocampus and sub-hippocampal areas, followed by neuronal lesions to the neocortical areas [6,7]. Current research nomenclature for AD includes preclinical AD, the earliest stage of AD in which biomarkers, such as amyloid and tau, are detectable through imaging data or cerebrospinal fluid (CSF), but no overt cognitive symptoms are indicated. Preclinical AD precedes another stage, termed prodromal AD where obvious cognitive symptoms emerge alongside aggregating neuropathological change. Finally, continuous neuropathological and cognitive changes culminate in clinical dementia towards the end of the AD continuum (see Figure 1 and [8]). Different research frameworks for AD have been proposed [9,10] (and references s11 and s12 in Online Supplementary Document), but the most recent criteria (ref. s12 in Online Supplementary Document) draw the strongest distinction between the biological construct of AD and the corresponding cognitive impairment or dementia syndromes that can accompany underlying disease changes as they evolve. This conceptual shift towards biomarker definitions of AD, away from its related cognitive syndromes, presents significant financial and logistical challenges for low-resourced research and clinical settings in LMiCs where disparate access to infrastructure, equipment and technical expertise required for biomarker capture exist. Consequently, LMiCs risk being excluded from participating in growing global efforts surrounding observational and interventional trials where biological criteria for AD are specified. Here, we consider possible approaches supported by neuropsychology and cognitive neuroscience to circumnavigate some of these challenges in the detection and tracking of AD in LMiC regions for research purposes.