Cognitive assessment in Alzheimer’s disease

No effective treatments are currently available to tackle Alzheimer's disease (AD), yet there seems to be a growing consensus in support to prevention initiatives [1-4]. This poses important challenges to the scientific community as prevention entails at least two targets, early detection and effective treatments neither of which meets current needs. Regarding the latter target, recent failures in clinical trials have led to question whether the under-taken treatments have been too little or too late [2,4]. This question seems to emerge from current understanding of the neuropathological changes underlying AD, which suggests that anti-amyloid treatments might need to be administered earlier than we thought [1]. However, to achieve this we first need to identify who could be suitable for such prevention trials and this requires early detection. Significant progress has been made in the area of biomarkers for AD, yet available tests still face important challenges [5-8]. Less has been done in the area of cognitive markers for AD, albeit cog-nition plays a fundamental role in the disease diagnosis, prognosis and follow up. The present short communication aims to reflect on current approaches to cognitive assessment in AD and the extent to which the conundrum " too little, too late " also applies to the early detection of cognitive impairments in this form of dementia. Traditional assessment of cognitive functions in AD has largely focused on episodic memory. This tendency has been driven by neuropathological evidence which suggests that regions within the medial temporal lobe known to be crucial from long-term memory formation are affected by AD since very early. However, episodic memory, as assessed by available tests, reveals impairments which characterize the rather advanced stages of the disease. It might be that for AD-related episodic memory changes to reach the pathological threshold of these tests, substantial damage to the hippocampus needs to accumulate because this structure and associated functions also decline as part of the normal aging process. Distilling age-related and AD-related decline of hippo-campal functions is a subject which requires further research. Moreover, the negative results currently reported by clinical trials might also rest, at least in part, on the outcome measures used to assess memory functions. The disease mechanisms tackled by available drugs (e.g., anti-amyloid compounds) might impact on brain regions and functions different from those taxed by available episodic memory tests [9-11]. Episodic memory tests might be unveiling the impact of advanced pathological changes (e.g., Tauopathy …