The tau S305S mutation causes frontotemporal dementia with parkinsonism.

Members of families with mutations in the tau gene are known to be heterogeneous in their clinical presentation, ranging from frontotemporal dementia to a clinical picture more resembling corticobasal degeneration or progressive supranuclear palsy. In this report, we describe a new phenotype for the tau S305S mutation, previously described as progressive supranuclear palsy. Clinically, the three affected family members showed alterations in personality and behaviour as well as cognitive decline and late levodopa-resistant parkinsonian symptoms, consistent with the diagnosis of frontotemporal dementia with parkinsonism linked to chromosome 17. One autopsied case displayed degeneration of the frontal and temporal lobes together with extensive tau pathology in both neurones and glial cells. Sarkosyl-soluble and -insoluble tau extracted from frontal cortex revealed a ratio shift with decreased levels of tau with three microtubule-binding repeats and increased levels of tau with four microtubule-binding repeats (4R tau). These findings provide further evidence for the clinical and pathological variation both within and between families with mutations in the tau gene. In addition, they support previous studies which demonstrate that the S305S mutation influences the splicing of tau exon 10 and results in an overproduction of 4R tau.

Temporary confusion: a fearful experience.

Older people admitted to hospital often develop acute temporary confusion. Earlier studies have focused on problems in providing care to the confused, causes of the confusion and the key aspects of caring. The aims of this study were to describe, from a nursing perspective, how older people experienced the phenomenon of temporary confusion and to describe the older peoples' reasoning when they described their experiences. Interviews with five older informants who had recovered from their confusional state were conducted and analysed using the phenomenological method. Two phenomena were studied, 'being temporarily confused' and 'reasoning about experiences of temporary confusion', each was found to be represented by four inter-related constituents. The phenomena can be understood as aspects of suffering and power imbalance between staff and older people.

Solid human embryonic spinal cord xenografts in acute and chronic spinal cord cavities: a morphological and functional study.

While therapeutic spinal cord grafting procedures are of interest in the chronic spinal cord injury stage, previous experimental grafting studies, including human spinal cord tissue, have mainly focused on the acute stage. Therefore, solid human embryonic spinal cord grafts were implanted in acute or chronic spinal cord aspiration cavities of immunodeficient rats to compare the morphological and locomotor outcome to that of lesion alone cases. Locomotor function was assessed using the Basso, Beattie, and Bresnahan open-field locomotor rating scale up to 6 months, while the morphological evaluation of graft survival, growth, and integration was performed at 6 weeks or 6 months after implantation. Graft survival was 94% in both lesion models, while graft growth was enhanced in the chronic compared to the acute cavity group. Human specific Thy-1 and neurofilament immunoreactive fibers were observed up to 7 mm into host white matter, while aminergic fibers were observed up to 1 mm into the grafts. Abundant calcitonin gene-related peptide immunoreactive fibers in the grafts in the absence both of immunoreactive cell bodies and colocalized human-specific neurofilament immunoreactivity, suggested host fiber ingrowth. At 6 months, the grafted cases presented less central canal deformation and lower glial fibrillary acidic protein immunoreactivity at the host cavity border compared to that of the nongrafted cases. The strong compensatory regain of locomotor function after unilateral spinal cord lesions was not affected by the human spinal cord grafts. In conclusion, solid human embryonic spinal cord tissue transplanted to a cavity in the adult injured spinal cord results in beneficial morphological effects in both the acute and chronic spinal cord lesion.

Nerve growth factor treatment in dementia.

Millions of people are affected by Alzheimer disease. As longevity increases, so will the number of patients with dementia. This has led to an intense search for successful treatment strategies. One area of interest is neurotrophic factors. Brain development and neuronal maintenance, as well as protective efforts, are mediated by a large number of different neurotrophic factors acting on specific receptors. In neurodegenerative disorders, there may be a possibility of rescuing degenerating neurons and stimulating terminal outgrowth with use of neurotrophic factors. The first neurotrophic factor discovered was nerve growth factor (NGF). A wealth of animal studies have shown that cholinergic neurons are NGF sensitive and NGF dependent, which is especially interesting in cognitive disorders, in which central cholinergic projections are important for cognitive function. In Alzheimer disease, cholinergic neurons have been shown to degenerate. This suggests that NGF may be used to pharmacologically counteract cholinergic degeneration and/or induce terminal sprouting in Alzheimer disease. Data from animal studies, as well as from the author's recent clinical trial, in which NGF was infused to the lateral ventricle in patients with Alzheimer disease, will be presented. Effects of NGF on cognition, as well as issues regarding dosage, side effects, and alternative ways of administering NGF, will be discussed.