A. Wallin

The aim was to study the frequently found white-matter changes on computerized tomography (CT) in patients with dementia and to relate these changes to clinical regional brain symptomatology, vascular factors, albumin ratio [indicator of blood-brain barrier (BBB) function] and other CT changes. The study included 85 patients, average age 71 ± 8, with Alzheimer’s disease (n = 56) and vascular dementia (n = 29), who underwent CT (Siemens Somatome DR 1) of the brain. They were inpatients in a psychiatric department specialized in dementia investigations. The degree of CT white-matter changes (absence, mild-moderate, severe) was the basis for the division of the patients into three groups. As the patients without white-matter changes were significantly younger than those with such changes, all statistical analyses were controlled for age. Subcortical symptomatology was significantly more frequent in the group with severe white-matter changes, whereas the reverse was true for parietal symptomatology. Diabetes mellitus, hypertension, ischemic cardiac disease and lacunas were significantly more common in patients with white-matter changes, whereas the freqeuncy of transient ischemic attack/stroke episodes did not differ significantly between the groups. The albumin ratio was significantly higher in the groups with white-matter changes and highest in the group with severe white-matter changes. The findings indicate that white-matter changes in demented patients are at least partially an age- and stroke-independent disease manifestation of the vascular system and is associated with a specific symptom pattern. BBB dysfunction may be the link between the vasculature and the tissue damage.

There is a need for improvement of the diagnosis of vascular dementia (VaD). Today, the clinician has to rely on clinical examination, history, and, possibly, brain imaging to identify cerebrovascular damage and other signs of VaD. The clinical diagnosis of subcortical VaD may be difficult because the clinical manifestation of this disorder is often similar to that of Alzheimer disease. There are also mixed forms of the two disorders. Biochemical diagnostic markers, which reflect the pathogenetic processes in the brain, would add to the accuracy of the diagnosis. There are some interesting candidate markers: the cerebrospinal fluid (CSF)/serum albumin ratio could be used to identify blood-brain barrier damage to the small intracerebral vessels, CSF sulfatide to identify ongoing demyelination of the white matter, CSF neuron-specific enolase to identify ongoing neuronal degeneration, and CSF tau protein and CSF neurofilament light protein to identify ongoing axonal degeneration. None of these potential markers is specific to subcortical VaD, but together and used in conjunction with the conventional diagnostic workup, they may be of diagnostic value.

Our hypothesis was that patients with vascular dementia and a dominating frontal lobe syndrome have a symptomatology that reflects a more widespread lesion compared with patients with frontotemporal dementia. Patients with vascular dementia and a dominating frontal lobe syndrome (VAD-F; N = 11) were compared with regard to clinical symptoms and imaging features on CT scans of the brain with patients with frontotemporal dementia (FTD; N = 21). A neuropsychiatric diagnostic ward. Thirty-two inpatients, aged 48-78 years, with frontotemporal dementia or vascular dementia. Relatives were questioned about the initial symptoms. At the clinical investigation, mental and neurological symptoms and signs were recorded using the STEP method (stepwise comparative status analysis). CT scan features of the brain were evaluated by a trained neuroradiologist. The GBS-i (Gottfries-Bråne-Steen, intellectual variables) scale was used to measure the degree of dementia. At the onset of dementia, loss of memory (p < 0.001), sudden onset (p < 0.001), confusion (p < 0.05) and unspecified neurological signs (p < 0.05) had been significantly more frequent in the VAD-F group. At the time of the clinical investigation, lack of social awareness and presence of primitive reflexes were more frequent in the FTD group (p < 0.01 and p < 0.05, respectively) and visuospatial deficits more frequent in the VAD-F group (p < 0.05). CT of the brain showed that, apart from brain infarcts (present only in the VAD-F group), paraventricular leukoaraiosis was significantly more pronounced in the VAD-F group (p < 0.05). The groups did not differ with respect to age, age at onset or level of dementia. The findings support our hypothesis.

In 40 patients with Alzheimer's disease (AD) 56 patients with senile dementia of Alzheimer type (SDAT) and 45 patients with vascular dementia (VAD) degree of dementia was rated into mild, moderate and severe according to DSM-III-R and on the GBS scale. Basal cortisol levels were determined and a dexamethasone test (DST) performed. Basal cortisol levels were high in all the dementia groups. Forty percent of AD patients, 54% of SDAT patients and 49% of VAD patients were non suppressors. Significant correlations between post DST cortisol levels and rated variables were seen mainly in the VAD group. The pathological DST could hardly be explained by presence of depression. In dementia, especially those with white matter disturbances, disconnections between cortical areas (hippocampus) and hypothalamus can be assumed explaining a reduced inhibitory tone on hypothalamus. When characterizing VAD patients with pathological DST these patients were significantly more intellectually impaired, showed higher degree of anxiety, restlessness and fear-panic than VAD patients with normal DST. Some behaviourial disturbances in dementia disorders may be a consequence of HPA over activity rather than a consequence of the dementia process itself.

Serum and cerebrospinal fluid (CSF) of 56 patients with dementia of the Alzheimer type (DAT) and 33 healthy controls were examined in order to investigate intra-blood-brain-barrier (intra-BBB) synthesis of immunoglobulins. Intra-BBB immunoglobulin G (IgG) synthesis was defined as an elevated IgG index (greater than 0.7) and/or presence of oligoclonal IgG in CSF but not in serum on isoelectric focusing, and intra-BBB immunoglobulin M (IgM) synthesis as an elevated IgM index (greater than 0.06). In total, 10 (18%) DAT patients displayed an intra-BBB immunoglobulin synthesis--five (9%) an IgG and five (9%) an IgM synthesis--but none among the controls. Also, the DAT patient group showed higher mean IgG and IgM indexes than the control group. These findings support the hypothesis that immunological mechanisms may play a role in the etiology and/or pathogenesis of Alzheimer disease, at least in a subgroup of patients.