Catarina Erikson

Cortical synaptic changes and gliosis in normal aging, Alzheimer's disease and frontal lobe degeneration

The most important new development during recent years in the field of degenerative dementia concerns synaptic pathology. So far it has been investigated in some regions and some cortical laminae in Alzheimers disease (AD). The present communication is a more comprehensive study of all laminae in four different regions, the prefrontal, parietal, inferior temporal and posterior cingulate cortex. Against the background of normal aging, AD was compared with another degenerative disorder, frontal lobe degeneration of non-Alzheimer type (FLD). The synapse density was measured using synaptophysin as a marker. Astrocytes were also counted in the molecular layer. In normals, the cortex showed successively lower synaptic density from layer I to layer VI and relatively lowest density in the prefrontal cortex and a general decline with increasing age. A 46-49% decrease in synaptic density was found in all laminae in all regions of AD brains, a finding different from that in FLD. The number of astrocytes increased significantly in the prefrontal cortex both in AD and FLD but parietally only in AD. These results contribute to the understanding of normal synaptic organization of cortex, demonstrate the laminar and regional distribution of synaptic loss in AD and underscore the difference between AD and FLD. The gliosis appears to be secondary to the neurodegenerative changes. Synaptic loss is likely to be a common pathogenetic feature of neurodegenerative disorders and a likely cause of clinical symptoms and regional metabolic decrements in dementia.

rCBF pathology in Alzheimer's disease is associated with slow processing speed

Decreased information processing speed (mental slowing) is a known sequelae of many brain disorders, and can be assessed by continuous naming tasks. Functional imaging studies have shown that pause and articulation times in continuous speech are normally associated with different brain regions, but knowledge about such association in dementia is lacking. We therefore tested the hypothesis that perfusion deficits in Alzheimers disease (AD) are not only associated with slower processing, but also with these speech measures. Using regional cerebral blood flow (rCBF) measurements during the performance of a continuous colour and form-naming task, we found that naming speed was substantially slower in AD patients than in controls. This slower naming was exclusively determined by an increase in mean pause time, and only to a limited extent by articulation time. The increased pause time was uniquely associated with temporo-parietal rCBF reductions of the patients, while articulation was not. By contrast, the rCBF of healthy elderly control subjects was consistently accompanied by substantially shorter articulation and pause times, although the naming measures were not statistically associated with rCBF. These findings suggest that pause time (in contrast to articulation time) may serve as a sensitive measure in the assessment of information processing speed deficits in dementia, by virtue of its close association with brain pathology.

A link between sICAM-1, ACE and parietal blood flow in the aging brain

A connection between Alzheimers disease (AD) and endothelium pathology has been inferred from measured decreases in both blood flow and metabolism in the parietal and temporal cortex. However, it is not known whether these alterations are seen in normal aging. We performed regional cerebral blood flow (rCBF) measurements in 22 AD patients and in 44 non-demented subjects during a simple test of information processing speed. Cerebrospinal fluid (CSF) levels of angiotensin-converting enzyme (ACE) and the soluble form of intercellular adhesion molecule-1 (sICAM-1) were analyzed in non-demented subjects. We found correlations between sICAM-1 and ACE (p=0.004), and sICAM (but not ACE) and CSF/plasma albumin ratio (p<0.0001). Higher concentrations of sICAM-1 (>893ng/L) and ACE (>5.22microg/L) were exclusively associated with lower parietal blood flow (p<0.001). The rCBF patterns in the AD and non-demented subjects with biomarker levels above median showed similar reductions in the temporoparietal areas. Our findings provide evidence that elevated CSF sICAM-1 and ACE are associated with lower perfusion levels in the parietal cortex of cognitively intact elderly.

The Accuracy of Short Clinical Rating Scales in Neuropathologically Diagnosed Dementia

OBJECTIVE The overall aim was to evaluate to what extent the diagnosis of dementia subtypes, obtained by three clinical rating scales, concurred with postmortem neuropathologic (NP) diagnosis of Alzheimer disease (AD), frontotemporal dementia (FTD), vascular dementia (VaD) and mixed AD/VaD. DESIGN A prospective longitudinal clinical work-up with postmortem NP examination. PARTICIPANTS Two hundred nine patients with dementia referred for clinical evaluation and follow-up. METHODS The diagnostic scores in a set of three short clinical rating scales for AD, FTD, and VaD were evaluated against NP diagnoses. RESULTS The sensitivity and specificity of the AD scale were 0.80 and 0.87, respectively, of the FTD scale 0.93 and 0.92, respectively, and of the Hachinski Ischemic Score (HIS, VaD diagnosis) 0.69 and 0.92, respectively. Cases with mixed AD/VaD generally presented a combination of high AD and ischemic scores. A preferred cutoff score of six was identified for both the AD and FTD scales. CONCLUSIONS All three clinical rating scales showed a high sensitivity and specificity, in close agreement with final NP diagnosis-for the HIS a moderate sensitivity. These scales may thus be considered good diagnostic tools and are recommended for clinical and research center settings.

A factor analytic approach to symptom patterns in dementia.

Previous publications have shown a high diagnostic sensitivity and specificity of three short clinical rating scales for Alzheimers disease (AD), frontotemporal dementia (FTD), and vascular dementia (VaD) validated against neuropathological (NP) diagnoses. In this study, the aim was to perform an exploratory factor analysis of the items in these clinical rating scales. The study included 190 patients with postmortem diagnoses of AD (n = 74), VaD (n = 33), mixed AD/VaD (n = 31), or FTD (n = 52). The factor analysis produced three strong factors. Factor 1 contained items describing cerebrovascular disease, similar to the Hachinski Ischemic Score. Factor 2 enclosed major clinical characteristics of FTD, and factor 3 showed a striking similarity to the AD scale. A fourth symptom cluster was described by perception and expression of emotions. The factor analyses strongly support the construct validity of the diagnostic rating scales.