Parkinsonism-dementia complex (PDC) and amyotrophic lateral sclerosis (ALS) are fatal neurological diseases. The incidence on Guam was very high between 1950 and 1965 but decreased dramatically after 1965. It is thought that drinking water containing low levels of calcium (Ca) and magnesium (Mg), and high levels of aluminum and of a plant excitatory neurotoxin are involved in the pathogenesis of these diseases. The present experiment was performed in rats that were exposed to low Ca and/or Mg intake over two generations, thus simulating the conditions of human life on Guam, where several generations live continuously in the same environment. Significant loss of dopaminergic neurons was identified exclusively in the substantia nigra in 1-year-old rats that had been exposed continuously to low Mg intake (one-fifth of the normal level) over generations. The present study suggests that low Mg intake over generations may be involved in the pathogenesis of substantia nigra degeneration in humans.

Metal analysis of calcium, manganese, aluminum and copper in CNS tissue samples of degenerative CNS disease cases (six Japanese ALS, three Japanese Alzheimer disease, four Guam PD, one Guam ALS) using neutron activation analysis, was conducted with following results: Five of six Japanese ALS cases, two of three Japanese Alzheimer disease cases and all of four Guam PD cases showed a high content of calcium and aluminum in CNS tissue with a significant positive correlation between calcium and aluminum and/or between calcium and manganese. These findings suggest a possible process of metal‐induced soft tissue calcification with interaction of other di‐ and/or trivalent cations such as aluminum, manganese in CNS tissue of these degenerative CNS diseases.

impulsivity is a neuropsychiatric feature of parkinson's disease (pD). We investigated the pathophysiology of impulsivity in pD using resting-state functional magnetic resonance imaging (rs-fMRI). We investigated 45 patients with idiopathic PD and 21 healthy controls. Based on Barratt Impulsiveness Scale (BIS-11) score, PD patients were classified as higher (PD-HI) or lower impulsivity (pD-Li). functional connectivity (fc) between various large-scale brain networks were analysed using the conn toolbox. fc between the right frontoparietal network (fpn) and medial visual network (MVN) was significantly higher in PD-HI patients than PD-LI patients (false discovery rate [FDR]adjusted p = 0.0315). FC between the right FPN and MVN had a significant positive correlation with total BIS-11 score (FDR-adjusted p = 0.010) and the attentional impulsivity (FDR-adjusted p = 0.046) and non-planning impulsivity subscale scores (fDR-adjusted p = 0.018). On the other hand, motor impulsivity subscale score had a significant negative correlation with the FC between the defaultmode and salience networks (right supramarginal gyrus, fDR-adjusted p = 0.018; anterior cingulate cortex, fDR-adjusted p = 0.027); this trend was observed in healthy controls. The attentional and non-planning impulsivity, regarded as 'cognitive' impulsivity, may be associated with dysfunction in integration of perceptual information and flexible cognitive control in PD.

Central nervous system tissue autopsy samples from seven Guam amyotrophic lateral sclerosis, four Guam Parkinsonism‐dementia complex and three Chamorro control cases were analyzed for aluminum, calcium, copper and manganese contents using the neutron activation analysis. ALS cases showed a high content of aluminum which corresponded to the area of degeneration in CNS tissue while calcium and manganese each showed a low content. PD cases showed a still higher content of aluminum, diffusely distributed. Copper and manganese levels were high while calcium showed a low content. The low calcium contents may be ascribed to the long period of formalin fixation. These findings support the indication that aluminum may participate in a CNS degenerative process of these diseases with interaction of other metals.

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