Metabolic Alterations in the Hypothalamus and Basal Forebrain in Vascular Dementia

Abstract

Previously, alterations in neuronal metabolism were found in a number of brain areas of Alzheimer disease (AD) patients. In the present study we aimed at determining for the first time whether metabolic changes would also occur in vascular dementia (VD) patients in the supraoptic (SON), infundibular (INF), tuberomamillary (TMN), medial mamillary nuclei, vertical limb of the diagonal band of Broca (VDB), and nucleus basalis of Meynert. The Golgi complex (GC) size, cell size, and vasopressin mRNA levels (in the SON) were used as measures of neuronal metabolic activity in postmortem material. The GC immunoreactivity was clearly diminished in the SON, INF and TMN and was increased in the VDB of VD cases. Interestingly, in the SON and TMN, a decrease in the GC size was more pronounced in male than in female VD patients in accordance with the higher prevalence of VD in men. In 7 of 11 VD cases, vasopressin mRNA levels were significantly reduced which may contribute to urinary incontinence, one of the most common clinical symptoms in VD, and to the lower blood pressure values that are often registered at the later stages of the VD. Since the human TMN is the sole source of cerebral histamine, our data suggest deficient histaminergic transmission in the brain in VD. Diminished neuronal metabolism in the SON and INF was not observed in AD in this and previous studies, whereas the changes in the VDB and TMN are similar in VD and AD. In the present study we thus found decreased metabolic activity in several hypothalamic nuclei in VD indicating diminished production of certain hormones and neurotransmitters.