Many of the treatments directed towards alleviation of symptoms in Alzheimer's disease assume that target receptor systems are functionally intact. However, there is now considerable evidence that this is not the case. In human post-mortem brain tissue samples, the function of the GTP-binding protein Gs in regulating adenylyl cyclase is severely disabled, whereas that of Gi is intact. This difference in the function of the two G-protein types is also found in G-protein regulation of high- and low-affinity receptor recognition site populations. Measurement of G-protein densities using selective antibodies has indicated that the dysfunction in Gs-stimulation of cAMP production correlates with the ratio of the large to small molecular weight isoforms of the Gs alpha subunit. With respect to intracellular second messenger effects, there is a dramatic decrease in the density of brain receptor recognition sites for Ins(1,4,5)P3 that is not accompanied by a corresponding change in the Ins(1,3,4,5)P4 recognition site density. Protein kinase C function is also altered in Alzheimer's disease, a finding that may be of importance for the control of beta-amyloid production. These studies indicate that signal transduction processes are severely compromised in Alzheimer's disease. Some of these disturbances are also seen in cultured fibroblasts from Alzheimer's disease patients, indicating that they are neither restricted to areas of histopathological change, nor non-specific changes found late in the course of the disease. Cellular models to investigate the relation between amyloid production and deficits in signal transduction are also discussed.

Alzheimer Disease↗

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Long-term adrenalectomy. Effect on cognitive behavior.

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Adrenalectomy↗

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Albumin and immunoglobulin in plasma and cerebrospinal fluid, and blood-cerebrospinal fluid barrier function in patients with dementia of Alzheimer type and multi-infarct dementia.

Plasma and cerebrospinal fluid (CSF) from 20 patients with Alzheimer's dementia or senile dementia of Alzheimer type (AD/SDAT), 23 with multi-infarct dementia (MID) and 16 controls were assayed for their content of immunoglobulins (Ig) and albumin (Alb). The concentrations of IgG and Alb were used to analyze the blood-CSF barrier function in the respective group. MID patients had significantly (P less than 0.001) elevated plasma IgG levels compared to controls and AD/SDAT patients. CSF concentration of Alb was significantly higher in MID (P less than 0.01) and AD/SDAT (P less than 0.05) patients compared to the controls. Concentration of CSF IgG was significantly (P less than 0.05) lower in AD/SDAT patients compared to the MID patients; no significant differences were found when CSF concentrations of IgG of demented patients were compared to controls. These findings may indicate a blood-CSF barrier dysfunction especially in cases with MID with significantly (P less than 0.001) elevated values of transudation. Also these findings indicate a non-specific and/or specific binding of IgG in CNS tissue and/or vessel walls in both forms of dementia on the basis of low IgG ratios compared to proportionally higher Alb ratios. There were no signs of local synthesis of IgG in CNS in either group of demented patients.

Aged↗

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Visuospatial functioning and spatial orientation in a community-based sample of healthy very old persons.

A population-based sample (n=219) of healthy older adults ranging from 75 to 96 years of age was examined in tests measuring visuospatial ability (modified Block Design Test) and spatial orientation (Clock Setting Test and Clock Reading Test). Results indicated an age-related deterioration in both visuospatial abilities and spatial orientation. Block Design performance was higher under self-paced than under paced conditions across the entire age range, although the beneficial effects from decreased pacing tended to increase with increasing age. Also, the clock test data suggest that the abilities underlying time recognition (clock reading) may deteriorate later in the normal aging process than those underlying time drawing (clock setting). Finally, regression analyses on the relationship between a variety of demographic, psychometric, and biological variables and visuospatial functioning showed that, in order of importance, years of age, Mini Mental State Examination (MMSE), and education, were significantly related to task performance.

Journal Article↗

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The short human figure drawing scale for evaluation of suspect cognitive dysfunction in old age.

Human figure drawings have been widely used to assess cognitive development in children. In the present study, free-hand human figure drawings were examined for 62 demented patients, and 60 normal elderly subjects. The drawings were scored for 53 body details using a method derived from work with children. A short scale of 15 details was developed by selecting body details with high item-total correlations which are simple to score even for untrained staff. This short scale had excellent interscorer and test-retest reliability and excellent concurrent validity as well. It correlated highly with the Mini-Mental State Examination, a commonly used screening test for dementia. The short scale discriminated demented and non-demented subjects and different levels of dementia severity as graded by the Clinical Dementia Rating Scale. However, no differences were observed between Alzheimer patients and patients with vascular dementia concerning presence of details in human figure drawings.

Journal Article↗

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Trail Making Test performance in a community-based sample of healthy very old adults: effects of age on completion time, but not on accuracy.

A population-based sample of healthy old adults ranging from 76 to 93 years of age (n=94) was examined in the Trail Making Test (TMT), and in tests assessing motor functions of the hands (the dynamic and optic-spatial organization of the motor act). Results indicated no age-related differences in TMT accuracy, although the time required to complete the test increased with increasing age. Similar patterns of results were observed for TMT-A and TMT-B. There were no age-related differences in the tests of hand-motor functioning, and subjects were carefully screened on visual and auditory capacity, hence making it unlikely that motor and sensory factors contributed to the results obtained. A test of visuo-spatial skill (Block Design Test) was marginally related to performance on TMT-B, whereas sex, education, a marker of global cognitive status (the Mini-Mental State Exam), and tests of primary memory (digit dpan forward and digit span backward) made no contribution to TMT performance. Several biological variables (e.g. vitamin B12, albumin, blood pressure) were also unrelated to TMT performance, although a positive relationship between thyroid stimulating hormone and TMT-B performance was documented. It was suggested that the influence of age on TMT speed may reflect age-related deficits in a variety of task-relevant skills, including perceptual speed, attentional functions (e.g. vigilance, concentration, visual scanning), and visuo-spatial ability.

Journal Article↗

PubMedDate not supplied

Copying and handwriting ability in the screening of cognitive dysfunction in old age.

Geometric copying and handwriting tests are often assessed in the screening of cognitive deficiency in the elderly. The aim of the study was to show the regression of geometrical copying and handwriting with increasing cognitive impairment in old age. The study is population-based and includes 668 subjects aged 75 years and older, living in an inner-city area of Stockholm. The subjects were asked to copy a cube, two pentagons, a rhombus, two intersecting rectangles, and a circle. They were also asked to write a complete sentence spontaneously, a sentence from dictation and their name. Geometric copying and handwriting skills decreased in direct proportion to decreased cognitive functioning. The skills most sensitive to small changes in cognition were copying the cube and the pentagons. Other skills were less sensitive to small changes: writing a complete sentence, copying a rhombus, two rectangles and writing one's name. However, copying and handwriting appear to complement each other. Copying of the rectangles and rhombus is more useful than the other figures because these two can be discriminated throughout different stages of dementia. Sentence writing from dictation and signature can be used to evaluate severely impaired subjects because these skills seem to be retained longer than the spontaneous sentence writing.

Journal Article↗