Reaction times, performance variability and attention measures: promising cognitive markers for the differentiation between normal aging and Alzheimer's disease?

Alzheimers disease (AD) is a neurodegenerative disease that leads to dementia. It is known that a long preclinical period with mild cognitive deficits precedes the clinical onset of the disease. Because it is assumed that treatment might function optimally in an early phase, preclinical detection of AD has become an important issue. Research has focussed mainly on the memory decline in AD since it is considered to be the hallmark of the disease. However, it becomes more and more obvious that other cognitive deficits may be detectable before clinical onset. Speed of processing, executive functioning and attention are believed to be potential interesting preclinical markers. Here we focus on reaction time (RT) measures, which can be operationalised in two ways, namely the standard level of performance and the performance variability. Three types of variability can be distinguished: diversity (or variability between persons), dispersion (variability across trials within one task) and inconsistency (variability across testing occasions). Particularly dispersion is assumed to be a sensitive marker of imminent conversion risk to AD. In our studies we wanted to demonstrate the clinical utility of the RT test (RTT), using a modified version of the RTT of van Zomeren with tasks of increasing complexity, which also allows differentiation of RT in a decision (DT) and a motor time (MT). In study 1 we described the effect of aging on RT and performance variability. Few studies have examined all types of variability within the same population. RT performance, inter- and intra- individual performance variability were compared for 27 older and 27 younger adults. There were consistent age and complexity differences for all variability types in our sample. When controlling for processing speed, which was slower in the older group, variability across age groups and task complexity tended to diminish and a more complex picture emerged. The elderly group showed a higher diversity of all RT measures, except for MT, and a higher dispersion of DT. Task complexity significantly affected the diversity of MT and overall RT and the dispersion of all RT measures, except for MT. These results highlight the importance of variability in cognitive functioning; it may be an important phenomenon for study and a useful indicator for cognitive deterioration. The reaction time test we proposed is easy to use and can be applied in clinical practice. Study 2 evaluated the discriminative power of attentional measures in the diagnosis of mild AD. Although recent studies also point to an important role of attention, besides memory deficits, early in the disease, this notion has not yet emerged in clinical practice. Our aim was to assess if attention, quantified by RT, can discriminate between patients with mild AD and controls and therefore contribute to clinical diagnosis. In a cross-sectional study, 33 patients with mild AD were matched with cognitively healthy elderly for age, gender, educational level and depressive mood. Selective attention (SA), alternating attention (AA) and error-rates were measured. Significant differences between both groups were found for all measures. Logistic regression showed that SA (corrected for individual processing speed), and error-rates could correctly classify subjects with an overall hit ratio of 81%. When attention measures were not corrected for individual processing speed, the overall hit ratio improved to 97%. Both SA and AA are deteriorated in patients with mild AD and these measures can discriminate between patients and matched controls, independently of depressive mood. In study 3 the clinical u