Homocysteine, Cognitive Functions, and Degenerative Dementias: State of the Art.

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.

Allochiria for spatial landmarks as the presenting feature of posterior cortical atrophy.

Allochiria refers to the mislocation of stimuli to the corresponding position on the opposite side of the body or hemispace. It is most often, although not exclusively, reported in the tactile modality and typically in association with unilateral neglect. We describe a patient presenting with a 2-year history of topographical disorientation without other cognitive complaints. We conducted a systematic exploration of his topographical problems to identify their cognitive substrate. Standard neuropsychological examination revealed no abnormalities. Notably, he performed well on perceptual, spatial, and constructional tasks. No signs of neglect were elicited. A tailored battery of tests was administered, involving road maps and landmarks, and designed to replicate the situations in which he experienced symptoms. The experimental tests showed no evidence of topographical agnosia or amnesia for landmarks and their spatial relationships and no hemispatial neglect. Nevertheless, the patient exhibited a systematic tendency to translocate topographical landmarks sited on the left to the right side. The phenomenon, consistent with representational allochiria, occurred exclusively for topographical landmarks, and was present along both personally familiar and new learned routes. Over the next two years more widespread visuoperceptual and spatial deficits emerged, with Balint and Gerstmann syndromes. Functional imaging revealed hypoperfusion of the occipito-parietal regions and amyloid PET the presence of amyloid plaques. A diagnosis was made of posterior cortical atrophy, the visual variant of Alzheimer's Disease. To our knowledge this is the first case of topographical disorientation presenting with selective representational allochiria and the first report of allochiria as an early sign of posterior cortical atrophy. The case sheds light on the cognitive basis of allochiria and on a puzzling clinical presentation of neurodegenerative brain disease.