Recollection-related hippocampal fMRI effects predict longitudinal memory change in healthy older adults

Prior fMRI studies have reported relationships between memory-related activity in the hippocampus and in-scanner memory performance, but whether such activity is predictive of longitudinal memory change remains unclear. Here, we administered a neuropsychological test battery to a sample of cognitively healthy older adults on three occasions, the second and third sessions occurring one month and three years after the first session. Structural and functional MRI data were acquired between the first two sessions. The fMRI data were derived from an associative recognition procedure and allowed estimation of hippocampal effects associated with both successful associative encoding and successful associative recognition (recollection). Baseline memory performance and memory change were evaluated using memory component scores derived from a principal components analysis of the neuropsychological test scores. Across participants, right hippocampal encoding effects correlated significantly with baseline memory performance after controlling for chronological age. Additionally, both left and right hippocampal associative recognition effects correlated negatively with longitudinal memory decline after controlling for age, and the relationship with the left hippocampal effect remained after also controlling for left hippocampal volume. Thus, in cognitively healthy older adults, the magnitude of hippocampal recollection effects appears to be a robust predictor of future memory change

The MOSDEF Survey:Optical AGN Diagnostics at z~2.3

We present results from the MOSFIRE Deep Evolution Field (MOSDEF) survey on rest-frame optical AGN identification and completeness at z~2.3. With our sample of 50 galaxies and 10 X-ray and IR-selected AGN with measured H-beta, [OIII], H-alpha, and [NII] emission lines, we investigate the location of AGN in the BPT, MEx (mass-excitation), and CEx (color-excitation) diagrams. We find that the BPT diagram works well to identify AGN at z~2.3 and that the z~0 AGN/star-forming galaxy classifications do not need to shift substantially at z~2.3 to robustly separate these populations. However, the MEx diagram fails to identify all of the AGN identified in the BPT diagram, and the CEx diagram is substantially contaminated at high redshift. We further show that AGN samples selected using the BPT diagram have selection biases in terms of both host stellar mass and stellar population, in that AGN in low mass and/or high specific star formation rate galaxies are difficult to identify using the BPT diagram. These selection biases become increasingly severe at high redshift, such that optically-selected AGN samples at high redshift will necessarily be incomplete. We also find that the gas in the narrow-line region appears to be more enriched than gas in the host galaxy for at least some MOSDEF AGN. However, AGN at z~2 are generally less enriched than local AGN with the same host stellar mass.Comment: 21 pages, 11 figures, updated to match ApJ accepted versio

The MOSDEF survey:AGN multi-wavelength identification, selection biases and host galaxy properties

We present results from the MOSFIRE Deep Evolution Field (MOSDEF) survey on the identification, selection biases, and host galaxy properties of 55 X-ray, IR and optically-selected active galactic nuclei (AGN) at $1.4 < z < 3.8$. We obtain rest-frame optical spectra of galaxies and AGN and use the BPT diagram to identify optical AGN. We examine the uniqueness and overlap of the AGN identified at different wavelengths. There is a strong bias against identifying AGN at any wavelength in low mass galaxies, and an additional bias against identifying IR AGN in the most massive galaxies. AGN hosts span a wide range of star formation rate (SFR), similar to inactive galaxies once stellar mass selection effects are accounted for. However, we find (at $\sim 2-3\sigma$ significance) that IR AGN are in less dusty galaxies with relatively higher SFR and optical AGN in dusty galaxies with relatively lower SFR. X-ray AGN selection does not display a bias with host galaxy SFR. These results are consistent with those from larger studies at lower redshifts. Within star-forming galaxies, once selection biases are accounted for, we find AGN in galaxies with similar physical properties as inactive galaxies, with no evidence for AGN activity in particular types of galaxies. This is consistent with AGN being fueled stochastically in any star-forming host galaxy. We do not detect a significant correlation between SFR and AGN luminosity for individual AGN hosts, which may indicate the timescale difference between the growth of galaxies and their supermassive black holes

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

Independent contributions of fMRI familiarity and novelty effects to recognition memory and their stability across the adult lifespan

The impact of age on the neural correlates of familiarity-driven recognition memory has received relatively little attention. Here, the relationships between age, the neural correlates of familiarity, and memory performance were investigated using an associative recognition test in young, middle-aged and older participants. Test items comprised studied, rearranged (items studied on different trials) and new word pairs. fMRI ‘familiarity effects’ were operationalized as greater activity for studied test pairs incorrectly identified as ‘rearranged’ than for correctly rejected new pairs. The reverse contrast was employed to identify ‘novelty’ effects. Estimates of familiarity strength were slightly but significantly lower for the older relative to the younger group. With the exception of one region in dorsal medial prefrontal cortex, fMRI familiarity effects (which were identified in medial and lateral parietal cortex, dorsal medial and left lateral prefrontal cortex, and bilateral caudate among other regions) did not differ significantly with age. Age-invariant ‘novelty effects’ were identified in the anterior hippocampus and the perirhinal cortex. When entered into the same regression model, familiarity and novelty effects independently predicted familiarity strength across participants, suggesting that the two classes of memory effect reflect functionally distinct mnemonic processes. It is concluded that the neural correlates of familiarity-based memory judgments, and their relationship with familiarity strength, are largely stable across much of the healthy adult lifespan

The relationships between age, associative memory performance, and the neural correlates of successful associative memory encoding

Using functional magnetic resonance imaging, subsequent memory effects (greater activity for later remembered than later forgotten study items) predictive of associative encoding were compared across samples of young, middle-aged, and older adults (total N = 136). During scanning, participants studied visually presented word pairs. In a later test phase, they discriminated between studied pairs, “rearranged” pairs (items studied on different trials), and new pairs. Subsequent memory effects were identified by contrasting activity elicited by study pairs that went on to be correctly judged intact or incorrectly judged rearranged. Effects in the hippocampus were age-invariant and positively correlated across participants with associative memory performance. Subsequent memory effects in the right inferior frontal gyrus (IFG) were greater in the older than the young group. In older participants only, both left and, in contrast to prior reports, right IFG subsequent memory effects correlated positively with memory performance. We suggest that the IFG is especially vulnerable to age-related decline in functional integrity and that the relationship between encoding-related activity in right IFG and memory performance depends on the experimental context

The Effects of Age on the Neural Correlates of Recollection Success, Recollection-Related Cortical Reinstatement, and Post-Retrieval Monitoring

Functional magnetic resonance imaging (fMRI) was used to investigate whether age-related differences in episodic memory performance are accompanied by a reduction in the specificity of recollected information. We addressed this question by comparing recollection-related cortical reinstatement in young and older adults. At study, subjects viewed objects and concrete words, making 1 of 2 different semantic judgments depending on the study material. Test items were words that corresponded to studied words or the names of studied objects. Subjects indicated whether each test item was recollected, familiar, or novel. Reinstatement of information differentiating the encoding tasks was quantified both with a univariate analysis of the fMRI signal and with a multivoxel pattern analysis, using a classifier that had been trained to discriminate between the 2 classes of study episode. The results of these analyses converged to suggest that reinstatement did not differ according to age. Thus, there was no evidence that specificity of recollected information was reduced in older individuals. Additionally, there were no age effects in the magnitude of recollection-related modulations in regional activity or in the neural correlates of post-retrieval monitoring. Taken together, the findings suggest that the neural mechanisms engaged during successful episodic retrieval can remain stable with advancing age

The neural correlates of recollection and retrieval monitoring: Relationships with age and recollection performance

The relationships between age, retrieval-related neural activity, and episodic memory performance were investigated in samples of young (18–29 yrs), middle-aged (43–55 yrs) and older (63–76 yrs) healthy adults. Participants underwent fMRI scanning during an associative recognition test that followed a study task performed on visually presented word pairs. Test items comprised pairs of intact (studied pairs), rearranged (items studied on different trials) and new words. fMRI recollection effects were operationalized as greater activity for studied pairs correctly endorsed as intact than for pairs incorrectly endorsed as rearranged. The reverse contrast was employed to identify retrieval monitoring effects. Robust recollection effects were identified in the core recollection network, comprising the hippocampus, along with parahippocampal and posterior cingulate cortex, left angular gyrus and medial prefrontal cortex. Retrieval monitoring effects were identified in the anterior cingulate and right dorsolateral prefrontal cortex. Neither recollection effects within the core network, nor the monitoring effects differed significantly across the age groups after controlling for individual differences in associative recognition performance. Whole brain analyses did however identify three clusters outside of these regions where recollection effects were greater in the young than in the other age groups. Across-participant regression analyses indicated that the magnitude of hippocampal and medial prefrontal cortex recollection effects, and both of the prefrontal monitoring effects, correlated significantly with memory performance. None of these correlations were moderated by age. The findings suggest that the relationships between memory performance and functional activity in regions consistently implicated in successful recollection and retrieval monitoring are stable across much of the healthy adult lifespan