BackgroundFahr’s disease is rare a neurodegenerative idiopathic condition characterized by symmetric and bilateral calcifications of basal ganglia, usually associated with progressive neuropsychiatric dysfunctions and movement disorders. The term “Fahr’s syndrome” is used in presence of calcifications secondary to a specific cause, but the variability of etiology, pathogenesis, and clinical picture underlying this condition have raised the question of the real existence of a syndrome. Several classifications based on the etiology, the location of brain calcifications and the clinical presentation have been proposed. Here we describe seven clinical cases of basal ganglia calcifications, in order to search for pathognomonic features and correlations between clinical picture and imaging findings.Cases presentationThe patients came to our attention for different reasons (most of them for memory/behavior disturbances); all underwent neuro-psychologic evaluation and neuro-imaging. All patients showed variable degrees of deterioration in cognitive function; anxiety and depression were frequent too, and resistant to treatment in all cases. Less frequent, but severe if present, were psychotic symptoms, with different grade of structure and emotional involvement, and always resistant to treatment. We observed only few cases of extrapyramidal disorders related to the disease itself; anyway, mild extrapyramidal syndrome occurred quite frequently after treatment with antipsychotics.ConclusionBased on these findings we discourage the use of the term “Fahr’s syndrome”, and suggest to refer to Idiopathic or Secondary basal ganglia calcification. Unlike early onset forms (idiopathic or inherited), the clinical presentation of late onset form and Secondary basal ganglia calcification seems to be really heterogeneous. Case–control studies are necessary to determine the actual significance of basal ganglia calcification in the adult population and in the elderly, in cognitive, physical and emotional terms.

The mechanisms linking diabetes and cognitive impairment/dementia, two common conditions of elderly people, are not completely known. Brain-derived neurotrophic factor (BDNF) has antidiabetic properties, and reduced circulating BDNF was associated with dementia. We investigated the relationship between plasma BDNF levels, dementia, and diabetes in a sample of 164 community-dwelling elderly individuals, including 50 participants with vascular dementia, 44 with late onset Alzheimer's disease, 23 with cerebrovascular disease not dementia, and 47 controls (C). Presence/absence of diabetes was registered; new diagnoses of diabetes were made by the American Diabetes Association criteria. BDNF plasma levels were measured by ELISA. Both diagnosis of dementia and diabetes were associated with lower BDNF plasma values compared with the respective controls; moreover, dementia and diabetes correlated with BDNF plasma levels, independent of possible confounders. A progressive reductions of BDNF plasma levels from C (383.9 ± 204.6 pg/mL), to cerebrovascular disease not dementia (377.1 ± 130.2), to vascular dementia (313.3 ± 114.8), to late onset Alzheimer's disease (264.7 ± 147.7) was observed, (late onset Alzheimer's disease vs C, p: .03; late onset Alzheimer's disease vs cerebrovascular disease not dementia, p: .002). Demented patients affected by diabetes had the lowest BDNF mean levels (264.9 pg/mL) among individuals enrolled in this sample, suggesting the existence of a "synergistic" effect of dementia and diabetes on BDNF levels.

Brain-derived neurotrophic factor (BDNF) is a member of the family of neurotrophins and has been implicated in brain resistance to insults. Murine studies have demonstrated increased hippocampal concentration after acute immobilization and decreased concentration after chronic immobilization. In humans, chronic stress and sedentary lifestyle result in decreased plasma BDNF levels, but there no data exist regarding acute immobilization. The aim of our study was to evaluate age-related responses [comparing 7 younger subjects (age 23 ± 3 yr) and 8 older subjects (age 60 ± 4 yr)] of plasma BDNF before (baseline data collection, BDC) and after 14 days (BR14) of horizontal bed rest (BR). At BDC, BDNF levels were not different between the two groups (P = 0.101), although at BR14, BDNF levels were higher in older subjects (62.02 ± 18.31) than in younger subjects (34.36 ± 15.24 pg/ml) (P = 0.002). A general linear model for repeated measures showed a significant effect of BR on BDNF (P = 0.002). The BDC BDNF levels correlated with fat-free mass in both populations (ALL) (R = 0.628, P = 0.012), (older, R = 0.753, P = 0.031; younger, R = 0.772, P = 0.042), and with total cholesterol in ALL (R = 0.647, P = 0.009) and older study subjects (R = 0.805, P = 0.016). At BR14, BDNF correlated with total cholesterol (R = 0.579, P = 0.024) and age (R = 0.647, P = 0.009) in ALL. With an increase in age, the brain could become naturally less resistant to acute stressors, including the detrimental effects of prolonged bed rest, and thus the increase in BDNF in the older study group might reflect a protective overshooting of the brain to counteract the negative effects in such conditions.

Acute stress, as bed rest, was shown to increase plasma level of the neurotrophin brain-derived neurotrophic factor (BDNF) in older, but not in young adults. This increase might represent a protective mechanism towards acute insults in aging subjects. Since computerized cognitive training (CCT) is known to protect brain, herein we evaluated the effect of CCT during bed rest on BDNF, muscle mass, neuromuscular function and metabolic parameters. The subjects that underwent CCT did not show an increase of BDNF after bed rest, and showed an anti-insular modification pattern in metabolism. Neuromuscular function parameters, already shown to beneficiate from CCT, negatively correlated with BDNF in research participants undergoing CCT, while positively correlated in the control group. In conclusion, BDNF increase can be interpreted as a standardized protective mechanism taking place whenever an insult occurs; it gives low, but consistent preservation of neuromuscular function. CCT, acting as an external protective mechanism, seems to modify this standardized response, avoiding BDNF increase or possibly modifying its time course. Our results suggest the possibility of differential neuroprotective mechanisms among ill and healthy individuals, and the importance of timing in determining the effects of protective mechanisms.