Inverse association between the anticholinergic burden and hippocampus volume in a population-based cohort across the entire adult age range.

Many medications of different indications have a relevant anticholinergic activity. The anticholinergic burden of medication has been shown to have significant effects on the cognition and the risk for cognitive impairment and dementia particularly in older patients. So far, most of the studies used data from geriatric patients and the effect of the anticholinergic burden on brain structures is still unexplored. Our study aimed to analyze possible associations of hippocampus and cholinergic basal forebrain volumes as vulnerable brain structures for the development of dementia and the anticholinergic burden in a population-based cohort of non-demented participants spanning the adult age range from 21 to 80 years. We analyzed associations between medication-related anticholinergic burden and structural MRI volumes from participants (n = 3087, 52.2% female) of the population-based "Study of Health in Pomerania" (SHIP). Anticholinergic burden was obtained from the current medication plan using the Anticholinergic Burden Scale (ACB). All analyses were adjusted for age, sex, education, and total intracranial volume. We found statistically significant associations between the ACB and the left and right hippocampus volume but not for the basal forebrain cholinergic system. Complementary voxel-based analysis across all participants revealed FWE-corrected (p = < 0.05) clusters in the temporo-parietal regions reaching into frontal areas, showing reduced volumes with higher ACB scores. We identified an association between anticholinergic burden of medication on hippocampal volume suggesting a potential inverse effect of such medication. This association highlights the importance of a careful prescription of medication with anticholinergic activity at any adult age.

Functional abnormalities of the visual processing system in subjects with mild cognitive impairment: an fMRI study.

Subjects with mild cognitive impairment (MCI) have a higher risk of developing Alzheimer's disease compared with healthy controls (HC). Sensory impairment can contribute to the severity of cognitive impairment. We measured the activation changes in the visual system between MCI and HC subjects. There were 16 MCI subjects with either amnestic MCI or multiple-domain+amnestic MCI and an HC group of 19 subjects. There were two tasks: (a) a face matching and (b) a location matching task. Brain activation was measured using functional magnetic resonance imaging. There were no differences in task performance. The HC group selectively activated the ventral and dorsal pathways during the face and location matching tasks, respectively, while the MCI group did not. The MCI group had greater activation than the HC group in the left frontal lobe during the location matching task. There were no areas of increased activation in the HC group compared with the MCI group. The MCI group, as a compensatory mechanism, activated both visual pathways and increased activation in the left frontal lobe during the location matching task compared with the healthy controls. To our knowledge, this is the first study that has examined visual processing in MCI.

Pattern of interleukin-6 receptor complex immunoreactivity between cortical regions of rapid autopsy normal and Alzheimer's disease brain.

Involvement of the interleukin-6 receptor complex (IL-6RC) in neuroregulatory and immunological processes of the brain and particularly in Alzheimer's disease (AD) has been hypothesized. The functionally active IL-6RC consists of the cytokine IL-6, which acts through the ligand binding IL-6R and the signal transducing gp130. Using a new immunocytochemical protocol on rapid autopsy cryostat brain sections we studied the expression of the IL-6RC in Braak IV-V staged AD patients compared to normal age-matched controls (HC) across five different cortical regions. Inter-rater reliability of the method was high. The "baseline" expression in normal human brain was determined for IL-6,IL-6R and gp130 in all cortical regions. In normal tissue IL-6 expression was lower in parietal cortex. Higher IL-6R expression was shown in frontal, occipital and parietal cortex, lower expression in temporal cortex and cerebellum. In AD IL-6 expression levels were generally increased in parietal cortex and decreased in occipital cortex compared to controls. IL-6R expression levels were strongly increased in AD frontal and occipital cortex and decreased in temporal cortex and cerebellum. Our findings indicate an altered cortical immunoreactivity pattern of the functional IL-6RC in AD supporting the hypothesis of a disease-related role of IL-6 in AD pathophysiology.