We investigated blood-brain barrier (BBB) function in relation to Alzheimer's disease (AD) and vascular dementia (VAD) in the very elderly. Sixty-five 85-year-old persons from a population-based sample were followed for 3 years; 29 were demented at age 85 (13 with AD, 14 with VAD, and 2 with other dementias), 7 developed dementia during follow-up, and 29 remained nondemented. CSF/serum albumin ratio was used as as a measure of BBB function. Dementia was defined according to the DSM-III-R, AD according to the NINCDS-ADRDA criteria, and VAD according to the NINDS-Association Internationale pour la Recherche et l'Enseignement en Neurosciences (AIREN) criteria. Mean CSF/serum albumin ratio was higher in all dementias (8.5 +/- 4.3; p = 0.007) and in the subtypes AD (8.9 +/- 5.3; p = 0.046) and VAD (8.7 +/- 3.5; p = 0.002) than in nondemented individuals (versus 6.5 +/- 2.0), but it was not related to dementia severity. Nondemented women at age 85 (n = 3) who developed dementia during the follow-up had a higher CSF/serum albumin ratio than those not developing dementia (10.4 +/- 2.0 versus 6.0 +/- 1.9; p = 0.007). Nondemented individuals lacking the apolipoprotein E epsilon3 allele (n = 4) had a higher CSF/serum albumin ratio (9.3 +/- 0.8 versus 6.6 +/- 2.1; p = 0.029) than other individuals. A relative BBB dysfunction is associated with both AD and VAD among very elderly individuals. This finding is possibly found early in the disease before the onset of clinical dementia.

Fifty-four patients with Alzheimer's disease (AD) were examined for white-matter lesions (WMLs) using computerized tomography. WMLs were more frequent in late-onset AD (LAD) (26/34-76%) than in early-onset AD (EAD) (5/20-25%) (p less than 0.0001), in AD without parietal predominance (10/11-91%) (p less than 0.005) than in AD with parietal predominance (5/15-33%), and in AD with confusional symptoms (11/12-92%) than in AD without confusional symptoms (4/14-29%) (p less than 0.001). The supine systolic blood pressure was higher in AD with WMLs (151 +/- 20) than in AD without WML (139 +/- 22) (p less than 0.05). AD patients with WMLs, but not those without WMLs, had a higher mean albumin ratio (7.5 +/- 2.7) than healthy controls (5.7 +/- 2.1) (p +/- 0.005). The finding of less focal (= less parietal) symptomatology in AD with WMLs than without WMLs suggests clinical significance of WMLs in AD, while the relations between blood pressure, BBB function and WMLs support the hypothesis of a vascular pathogenesis.

In 336 consecutive patients attending a university-affiliated memory unit, clinical and psychological findings, neuroimaging and laboratory tests were analyzed. The patients were diagnosed with early Alzheimer’s disease 3%, senile dementia (SDAT) 16%, vascular dementia (VAD) 20%, other dementias 9%, minor cognitive impairment (dysmentia) 32% and subjective symptoms only 21%. Increases in vascular risk factors, serum homocysteine, ApoE4 load and neuroimaging pathology were found in dementia but also in dysmentia and in patients with subjective symptoms only. The homocysteine levels correlated inversely with cognitive performance. The increases in serum homocysteine, which were pathological in VAD, Dysmentia and SDAT, may be indicative of a disturbed cerebral one-carbon metabolism and signal-accelerated development of cognitive disease.

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Thirty patients had mild cognitive impairment and increased homocysteine levels in serum. On average, they were supplemented orally with a high dose of a vitamin B₁₂-B₆-folate combination for 270 days. All patients had normal serum B₁₂ and folate levels at baseline. Cerebrospinal fluid levels of the tau protein (CSF-tau) and the albumin ratio were measured before and after treatment. The serum homocysteine levels were normalised after treatment. The albumin ratio significantly correlated with vascular risk factors. At baseline, the ratio was higher in the patients in comparison with age-matched controls. After treatment, the ratio was significantly reduced, which may indicate a tightening of the blood-brain barrier. The CSF-tau levels did not change significantly although there was a numeric decline. None of the patients progressed into dementia during the treatment period. When treated with a vitamin B₁₂-B₆-folate combination, patients with mild cognitive impairment and hyperhomocysteinaemia appear to improve their blood-brain barrier function. They may also stabilise their cognitive status. Further investigations are warranted on the role of blood-brain barrier dysfunction in the pathogenesis of dementia.

Different nuclei and regions of the brain from patients who had committed suicide and from controls were analysed for their content of monoamine and monoamine metabolites. There was a post mortem breakdown of 5-hydroxyindoleacetic acid (5-HIAA) which could be correlated to the time elapsed between the occurrence of death and autopsy. Homovanillic acid (HVA) and the monoamines did not decrease post mortem during the time observed (6-148 hours). There was no significant correlation between age and chemical variables in this investigation. There were no significant group differences between suicides and controls concerning dopamine, noradrenaline, 5-hydroxytryptamine, and HVA, 5-HIAA levels were significantly lower in the suicide group in six out of eight parts of the brain investigated. It was, however, also demonstrated that there was a longer time elapse between the occurrence of death and autopsy in the suicide group. The suicides came on average 48 hours later to autopsy than the controls. As there was a post mortem decrease of 5-HIAA, this time variable had to be kept constant when group differences were analysed. When the influence of this time variable was eliminated there were no longer any differences between suicides and controls. According to this investigation, there seem to be no differences in levels of monoamines and their metabolites between suicides and controls.

The lipid composition of white matter and myelin from the semioval centre was studied in autopsy material from cases with Alzheimer's disease (AD) (n = 11), vascular dementia (VD) (n = 7), and age-matched controls (n = 11). In AD and VD the white matter content of phospholipids and cholesterol was reduced to 72-76% of the control values (P less than 0.01), the diminution of cerebrosides and sulphatides was more pronounced (55-69%) (P less than 0.001) while the concentration of gangliosides did not change significantly (87-90%). The myelin composition was the same in the 3 groups, suggesting that the white matter involvement is not caused by alteration of the myelin structure. The altered lipid composition in white matter in AD and VD suggests that the myelin sheath is the primary lesion site.