Declining brain glucose metabolism in normal individuals with a maternal history of Alzheimer disease.

BACKGROUND: At cross-section, cognitively normal individuals (NL) with a maternal history of late-onset Alzheimer disease (AD) have reduced glucose metabolism (CMRglc) on FDG-PET in the same brain regions as patients with clinical AD as compared to those with a paternal and a negative family history (FH) of AD. This longitudinal FDG-PET study examines whether CMRglc reductions in NL subjects with a maternal history of AD are progressive. METHODS: Seventy-five 50- to 82-year-old NL received 2-year follow-up clinical, neuropsychological, and FDG-PET examinations. These included 37 subjects with negative family history of AD (FH-), 9 with paternal (FHp), and 20 with maternal AD (FHm). Two subjects had parents with postmortem confirmed AD. Statistical parametric mapping was used to compare CMRglc across FH groups at baseline, follow-up, and longitudinally. RESULTS: At both time points, the FH groups were comparable for demographic and neuropsychological characteristics. At baseline and at follow-up, FHm subjects showed CMRglc reductions in the parieto-temporal, posterior cingulate, and medial temporal cortices as compared to FH- and FHp (p < 0.001). Longitudinally, FHm had significant CMRglc declines in these regions, which were significantly greater than those in FH- and FHp (p < 0.05). CONCLUSIONS: A maternal history of Alzheimer disease (AD) predisposes normal individuals to progressive CMRglc reductions in AD-vulnerable brain regions, which may be related to a higher risk for developing AD.

Longitudinal CSF isoprostane and MRI atrophy in the progression to AD.

Very little data exist to evaluate the value of longitudinal CSF biological markers for Alzheimer's disease (AD). Most studies indicate that tau and amyloid beta markers do not reflect disease progression. We now report on a longitudinal, three-time point, CSF Isoprostane (IsoP) and quantitative MRI study that examined 11 normal elderly (NL) volunteers and 6 Mild Cognitive Impairment (MCI) patients. After 4 years, all 6 MCI patients declined to AD and 2 of the NL subjects declined to MCI. At baseline and longitudinally, the MCI patients showed reduced delayed memory, increased IsoP levels, and reduced medial temporal lobe gray matter concentrations as compared to NL. A group comprised of all decliners to AD or to MCI (n = 8) was distinguished at baseline from the stable NL controls (n = 9) by IsoP with 100% accuracy.Moreover, both at baseline and longitudinally, the IsoP measures significantly improved the diagnostic and predictive outcomes of conventional memory testing and quantitative MRI measurements. These data indicate that IsoP is potentially useful for both the early detection of AD-related pathology and for monitoring the course of AD.

Generalization of conditioned suppression after differential training.

In a modified conditioned suppression procedure, clicks at one frequency (danger signal) preceded shocks, while no shocks followed clicks at a different frequency (safe signal). During generalization tests, the maximal response rate was frequently shifted from the safe signal in the direction away from the danger signal, and the minimal response rate was frequently shifted in the opposite direction, away from the safe signal. There was considerable variability in the results from one animal to another. The generalization tests also suggested different generalization functions according to whether the danger signal was a lower or a higher frequency than the safe signal. The results also showed the development of systematic differences in response rate during and after the safe and danger signals, notably a relatively high rate at the beginning of the safe signal and after the danger signal.

Stimulus control in the goldfish after massed extinction.

Compared with the data of goldfish trained only with stimuli correlated with reinforcement, interspersed reinforcement-stimulus and extinction-stimulus trials resulted in sharper stimulus control and a marked reduction in the percentage of key-presses emitted in the presence of stimuli located near the extinction stimulus on the test dimension. If non-reinforced trials were not interspersed with reinforced trials, there was no sharpening of stimulus control and less reduction in key presses in the presence of stimuli near the extinction stimulus on the test dimension.

Periodic shock with added clock.

Rats were shocked every 6 min while responding was maintained on a variable-interval schedule of reinforcement. With some rats, shocks were interspersed with a sequence of three different stimulus conditions (S3-->S2-->S1), or clock cues, each lasting 2 min. For other rats, a single stimulus condition prevailed between shocks at the beginning of the experiment and clock cues were introduced later. Response rate decreased from S3 to S1. Response rate in S3, S2, and S1 was inversely related to shock intensity. When clock cues were added, response rate increased in all 2-min intershock periods. During clock cues, an index of curvature, indicating the degree of negative acceleration of response rate, was greatest for S1 and least for S3, and was directly related to shock intensity. The response-facilitating effect of shock and its relation to a possible discriminative function of shock and to behavioral contrast is discussed.