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ABSTRACTObjectives:Individuals with Alzheimer's disease (AD) present poor immediate primacy recall accompanied by intact or exaggerated recency, which then tends to decline after a delay. Bruno et al. (Journal of Clinical and Experimental Neuropsychology, Vol. 38, 2016, pp. 967-973) have shown that higher ratio scores between immediate and delayed recency (i.e. the recency ratio; Rr) are associated with cognitive decline in high-functioning older individuals. We tested whether Rr predicted conversion to early mild cognitive impairment (early MCI) from a cognitively healthy baseline., Design: Data were analyzed longitudinally with binomial regression. Baseline scores were used to predict conversion to early MCI after approximately nine years., Setting: Data were collected at the Wisconsin Registry of Alzheimer's Prevention, in Madison, Wisconsin., Participants: For the study, 427 individuals were included in the analysis; all participants were 50 years of age or older and cognitively intact at baseline, and were native English speakers., Measurements: Memory data were collected using the Rey's Auditory Verbal Learning Test, and the early MCI diagnosis was obtained via consensus conference., Results: Our results showed that higher Rr scores are correlated with greater risk of later early MCI diagnosis, and this association is independent of total recall performance., Conclusions: Rr is an emerging cognitive marker of cognitive decline.

Glutamate is the principal excitatory neurotransmitter in the central nervous system, and is thought to be involved in the process of memory encoding and storage. Glutamate disturbances have also been reported in psychiatric disorders, such as schizophrenia and major depressive disorder (MDD), and in Alzheimer's disease. In this paper, we set out to study the relationship between cerebrospinal fluid (CSF) glutamate levels and memory performance, which we believe has not been reported previously. In particular, we focused on recall performance broken down by serial position. Our prediction was that the recency ratio (Rr), a novel cognitive marker of intellectual impairment, would be linked with CSF glutamate levels. We studied data from a group of cognitively intact elderly individuals, 28 of whom had MDD, while 19 were controls. Study results indicated that Rr levels, but no other memory score, were inversely correlated with CSF glutamate levels, although this was found only in individuals with late-life MDD. For comparison, glutamine or GABA were not correlated with any memory performance measure., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Individuals with Alzheimer's disease have been found to present a typical serial position curve in immediate recall tests, showing poor primacy performance and exaggerated recency recall. However, the recency advantage is usually lost after a delay. On this basis, we examined whether the recency ratio (Rr), calculated by dividing recency performance in an immediate memory task by recency performance in a delayed task, was a useful risk marker of cognitive decline. We tested whether change in Mini-Mental State Examination (MMSE) performance between baseline and follow-up was predicted by baseline Rr and found this to be the case (N = 245). From these analyses, we conclude that participants with high Rr scores, who show disproportionate recency recall in the immediate test compared to the delayed test, present signs of being at risk for cognitive decline or dysfunction.

Adapted from the work of Kahana and colleagues (e.g., Kahana, 1996), we present two measures of order of recall in neuropsychological free recall tests. These are the position on the study list of the first recalled item, and the degree of variability in the order in which items are reported at test (i.e., the temporal distance across the first four recalled items). We tested two hypotheses in separate experiments: (1) whether these measures predicted generalized cognitive ability, and (2) whether they predicted gray matter hippocampal volume. To test hypothesis 1, we conducted ordinal regression analyses on data from a group of 452 participants, aged 60 or above. Memory performance was measured with Rey's AVLT and generalized cognitive ability was measured with the MMSE test. To test hypothesis 2, we conducted a linear regression analysis on data from a sample of 79 cognitively intact individuals aged 60 or over. Memory was measured with the BSRT and hippocampal volume was extracted from MRI images. Results of Experiment 1 showed that the position of the first item recalled and the degree of output order variability correlated with MMSE scores only in the delayed test, but not in the immediate test. In Experiment 2, the degree of variability in the recall sequence of the delayed trial correlated (negatively) with hippocampal size. These findings confirm the importance of delayed primacy as a marker of cognitive ability, and are consistent with the idea that the hippocampus is involved in coding the temporal context of learned episodes., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objective: There is evidence of more widespread use and abuse of benzodiazepines (BZPs) among elderly women. However, factors underlying this observation are poorly understood but could be related to more intense withdrawal reactions, which are a major risk factor for continued BZP use. We previously reported elevations in interdose morning plasma cortisol levels in healthy elderly individuals after chronic treatment with alprazolam, possibly consistent with increased hypothalamic-pituitary-adrenal (HPA) axis activity and drug withdrawal. In this study, we examined sex-related differences in this population., Method: Twenty-five cognitively intact healthy elderly (13 women and 12 men) participated in a parallel, double-blind, placebo-controlled study that included a group that received acute and chronic (3 weeks) treatment with alprazolam (0.5 mg b.i.d.)., Results: Elderly women, but not men, experienced significant elevations in interdose morning plasma cortisol levels over 3 weeks of chronic treatment with alprazolam (0.5 mg b.i.d.) compared to placebo. In addition, higher morning plasma cortisol levels were significantly associated with better cognitive performance but not with higher plasma drug levels or greater degree of tolerance development to an acute alprazolam challenge., Conclusion: Elderly females experienced a greater interdose activation of the HPA axis during treatment with therapeutic doses of alprazolam than men, which could be related to drug withdrawal.

The GABA system is an active target for drugs to treat a variety of disorders and the availability of an indirect measure of central GABA activity would not only enhance psychiatric research, but also permit assessment of the pharmacodynamic effects of drugs designed to act on this system. The relationships between plasma baseline pre-drug GABA concentrations and cognitive impairments induced by an acute oral dose of lorazepam (0.5 and 1.0 mg) were investigated in 22 healthy elderly individuals. Partial correlations controlling for plasma lorazepam concentrations revealed no significant relationship between baseline plasma GABA levels and lorazepam-induced impairments on tests of cognitive functioning. Plasma GABA concentration does not appear to be a useful marker of susceptibility to benzodiazepine-induced cognitive toxicity in the elderly. Other approaches to estimating central GABA activity should be pursued.

The effects of acute lorazepam challenges on plasma (p) HVA, MHPG, and 5-HIAA, and their relationship to drug-induced cognitive and motor deficits and the apolipoprotein (APOE)-epsilon4 allele were examined. Eighteen healthy elderly (8 epsilon4 carriers) received placebo or acute oral lorazepam doses (0.5 mg or 1 mg) in random sequence, 1-week apart. Cognitive assessment and plasma levels of pHVA, pMHPG, and p5-HIAA were determined at baseline and at 1, 2.5, and 5 h postchallenge. There was no drug-to-placebo difference in monoamine levels and no consistent relationship between changes in monoamine levels and cognitive performance, regardless of epsilon4 status. However, the 1.0 mg dose increased p5-HIAA in epsilon4 carriers, whereas it caused a reduction in noncarriers. Higher baseline pMHPG and p5-HIAA levels were associated with better baseline memory. The epsilon4 allele may modulate the effect of lorazepam on p5-HIAA, but further studies are needed to confirm this finding and elucidate its possible significance.