Comparing Symmetric Dimethylarginine and Amyloid-ß42 as Predictors of Alzheimer's Disease Development.

Background: Physicians may soon be able to diagnose Alzheimer's disease (AD) in its early stages using fluid biomarkers like amyloid. However, it is acknowledged that additional biomarkers need to be characterized which would facilitate earlier monitoring of AD pathogenesis. Objective: To determine if a potential novel inflammation biomarker for AD, symmetric dimethylarginine, has utility as a baseline serum biomarker for discriminating prodromal AD from cognitively unimpaired controls in comparison to cerebrospinal fluid amyloid-ß42 (Aß42). Methods: Data including demographics, magnetic resonance imaging and fluorodeoxyglucose-positron emission tomography scans, Mini-Mental State Examination and Functional Activities Questionnaire scores, and biomarker concentrations were obtained from the Alzheimer's Disease Neuroimaging Initiative for a total of 146 prodromal AD participants and 108 cognitively unimpaired controls. Results: Aß42 (p = 0.65) and symmetric dimethylarginine (p = 0.45) were unable to predict age-matched cognitively unimpaired controls and prodromal AD participants. Aß42 was negatively associated with regional brain atrophy and hypometabolism as well as cognitive and functional decline in cognitively unimpaired control participants (p < 0.05) that generally decreased in time. There were no significant associations between Aß42 and symmetric dimethylarginine with imaging or neurocognitive biomarkers in prodromal AD patients. Conclusions: Correlations were smaller between Aß42 and neuropathological biomarkers over time and were absent in prodromal AD participants, suggesting a plateau effect dependent on age and disease stage. Evidence supporting symmetric dimethylarginine as a novel biomarker for AD as a single measurement was not found.

Pathological Joking or Witzelsucht Revisited.

Humor, or the perception or elicitation of mirth and funniness, is distinguishable from laughter and can be differentially disturbed by neuropsychiatric disease. The authors describe two patients with constant joking, or Witzelsucht, in the absence of pseudobulbar affect and review the literature on pathological humor. These patients had involvement of frontal structures, impaired appreciation of nonsimple humor, and a compulsion for disinhibited joking. Current neuroscience suggests that impaired humor integration from right lateral frontal injury and disinhibition from orbitofrontal damage results in disinhibited humor, preferentially activating limbic and subcortical reward centers. Additional frontal-subcortical circuit dysfunction may promote pathological joking as a compulsion.