There is strong evidence that homocysteine is a risk factor not only for cerebrovascular diseases but also for degenerative dementias. A recent consensus statement renewed the importance and the role of high levels of homocysteine in cognitive decline in several forms of degenerative dementia, such as Alzheimer’s disease. Although the molecular mechanisms by which homocysteine causes cell dysfunction are known, both the impact of homocysteine on specific cognitive functions and the relationship between homocysteine level and non-Alzheimer dementias have been poorly investigated. Most of the studies addressing the impact of hyperhomocysteinemia on dementias have not examined the profile of performance across different cognitive domains, and have only relied on screening tests, which provide a very general and coarse-grained picture of the cognitive status of the patients. Yet, trying to understand whether hyperhomocysteinemia is associated with the impairment of specific cognitive functions would be crucial, as it would be, in parallel, learning whether some brain circuits are particularly susceptible to the damage caused by hyperhomocysteinemia. These steps would allow one to (i) understand the actual role of homocysteine in the pathogenesis of cognitive decline and (ii) improve the diagnostic accuracy, differential diagnosis and prognostic implications. This review is aimed at exploring and revising the state of the art of these two strictly related domains. Suggestions for future research are provided.
Developmental dyslexia can be viewed as the result of the effects of single deficits or multiple deficits. This study presents a test of the applicability of a multifactor-interactive model (MFi-M) with a preliminary set of five variables corresponding to different neuropsychological functions involved in the reading process. The model has been tested on a sample of 55 school-age children with developmental dyslexia. The results show that the data fit a model in which each variable contributes to the reading ability in a non-additive but rather interactive way. These findings constitute a preliminary validation of the plausibility of the MFi-M, and encourage further research to add relevant factors and specify their relative weights. It is further discussed how subtype-based intervention approaches can be a suitable and advantageous framework for clinical intervention in a MFi-M perspective.
Unilateral neglect is usually investigated by adminstering stimuli (targets) in different positions, with targets being responded to by the patient (Hit) or omitted. In spite of this homogeneity of data type, neglect indices and diagnostic criteria vary considerably, causing inconsistencies in both clinical and experimental settings. We aimed at deriving a standard analysis which would apply to all tasks sharing this data form. A-priori theoretical reasoning demonstrated that the mean position of Hits in space (MPH) is an optimal index for correctly diagnosing and quantifying neglect. Crucially MPH eliminates the confounding effects of deficits that are different from neglect (non-lateral) but which decrease Hit rate. We ran a Monte Carlo study to assess MPH's (so far overlooked) statistical behavior as a function of numbers of targets and Hits. While average MPH was indeed insensitive to non-lateral deficits, MPH's variance (like that of all other neglect indices) increased dramatically with increasing non-lateral deficits. This instability would lead to alarmingly high false-positive rates (FPRs) when applying a classical diagnostic procedure that compares one patient with a control sample. We solved the problem by developing an equation that takes into account MPH instability and provides correct cut-offs and close-to-nominal FPRs, even without control subjects. We developed a computerized program which, given the raw data, yields the MPH, a z-score and a p-value. We provided a standard method that allows clinical and experimental neuropsychologists to diagnose and measure neglect in a consistent way across the vast majority of tasks.