No abstract

BackgroundEarly treatment of Alzheimer’s disease may reduce its devastating effects. By focusing research on asymptomatic individuals with Alzheimer’s disease pathology (the preclinical stage), earlier indicators of disease may be discovered. Decreasing cerebrospinal fluid beta-amyloid42 is the first indicator of preclinical disorder, but it is not known which pathology causes the first clinical effects. Our hypothesis is that neuropsychological changes within the normal range will help to predict preclinical disease and locate early pathology.Methods and FindingsWe recruited adults with probable Alzheimer’s disease or asymptomatic cognitively healthy adults, classified after medical and neuropsychological examination. By logistic regression, we derived a cutoff for the cerebrospinal fluid beta amyloid42/tau ratios that correctly classified 85% of those with Alzheimer’s disease. We separated the asymptomatic group into those with (n = 34; preclinical Alzheimer’s disease) and without (n = 36; controls) abnormal beta amyloid42/tau ratios; these subgroups had similar distributions of age, gender, education, medications, apolipoprotein-ε genotype, vascular risk factors, and magnetic resonance imaging features of small vessel disease. Multivariable analysis of neuropsychological data revealed that only Stroop Interference (response inhibition) independently predicted preclinical pathology (OR = 0.13, 95% CI = 0.04–0.42). Lack of longitudinal and post-mortem data, older age, and small population size are limitations of this study.ConclusionsOur data suggest that clinical effects from early amyloid pathophysiology precede those from hippocampal intraneuronal neurofibrillary pathology. Altered cerebrospinal fluid beta amyloid42 with decreased executive performance before memory impairment matches the deposits of extracellular amyloid that appear in the basal isocortex first, and only later involve the hippocampus. We propose that Stroop Interference may be an additional important screen for early pathology and useful to monitor treatment of preclinical Alzheimer’s disease; measures of executive and memory functions in a longitudinal design will be necessary to more fully evaluate this approach.

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Background: Cerebrospinal fluid (CSF) contacts many brain regions and may mediate humoral signaling distinct from synaptic neurotransmission. However, synthesis and transport mechanisms for such signaling are not defined. The purpose of this study was to investigate whether human CSF contains discrete structures that may enable the regulation of humoral transmission.

Background.-Pharmaceuticals with calcium-or sodium-channel-blocking activity have proven useful for migraine prophylaxis, and calcium channel, sodium transporter, and sodium channel gene mutations have been found in familial hemiplegic migraine. However, it is not known whether calcium or sodium homeostasis is altered in migraine.Objective.-To compare levels of sodium, calcium, potassium, and magnesium in cerebrospinal fluid (CSF) and blood plasma between migraineurs and controls.Methods.-We recruited 20 migraineurs without aura and 11 controls prospectively, and studied migraineurs in sick (MH + ) and well (MH − ) states. We collected lumbar CSF and venous blood plasma, quantified elements with ion-selective electrodes or colorimetry, and determined osmolality by depression of freezing point. We compared levels of Na + , Ca 2+ , K + , and Mg among and also within subjects who were studied in both MH + and MH − states.Results.-Mean CSF Na + levels were increased by 3 mmol/L in MH + compared with MH − and by 4 mmol/L compared to controls (P < 0.005). In 4 subjects who were sampled in both MH + and MH − states, mean CSF Na + concentration increased by 2 mmol/L in the MH + state compared with the MH − state (P < 0.05). Simultaneous plasma Na + levels did not differ among the 3 clinical groups, nor did osmolality, total Ca and Ca 2+ , K + , and total Mg levels in CSF.Conclusions.-Compared to both controls and the MH − state, CSF Na + concentration increased in MH + independently from other clinical or pharmacological fluctuations, CSF concentrations of Ca 2+ , Mg, and K + , and blood plasma Na + levels. These results implicate a deviation of Na + homeostasis in migraine. The modestly elevated extracellular Na + in MH + may cause the neural changes that underlie clinical features of migraine.