Late-life depression (LLD) is associated with an increased risk of developing dementia; however, it is not known whether individuals with a history of LLD exhibit a more rapid rate of cognitive decline. We aimed to determine whether those with LLD experienced faster cognitive decline compared with never-depressed control (NDC) participants from the community and whether stratification of LLD into early-onset depression (EOD) and late-onset depression (LOD) subtypes revealed differing rates and domain-specific expression of cognitive decline. We conducted a prospective, longitudinal study where 185 participants with LLD (remitted) and 114 NDC were followed for 5 years on average. EOD was defined as having first lifetime depressive episode at <60years and LOD at ≥60years. Every year, participants underwent comprehensive neuropsychological assessment. Composite scores for each cognitive domain were calculated through averaging standardized scores across tests. LLD compared to NDC demonstrated significant baseline impairment but did not decline more rapidly. EOD were significantly impaired in attention/processing speed and global cognitive function at baseline but did not experience more rapid decline as compared to NDC. Those with LOD compared to both NDC and EOD performed worse in all domains at baseline and experienced more rapid decline in verbal skills and delayed memory ability. Our findings suggest that baseline impairment may lower the threshold for those with LLD to develop dementia. EOD and LOD may represent distinct phenotypes of cognitive impairment with differing neural substrates. LOD may represent a distinct phenotype with a more rapid decline in verbal skills and delayed memory.

The Muller F element (4.2 Mb, ~80 protein-coding genes) is an unusual autosome of Drosophila melanogaster; it is mostly heterochromatic with a low recombination rate. To investigate how these properties impact the evolution of repeats and genes, we manually improved the sequence and annotated the genes on the D. erecta, D. mojavensis, and D. grimshawi F elements and euchromatic domains from the Muller D element. We find that F elements have greater transposon density (25–50%) than euchromatic reference regions (3–11%). Among the F elements, D. grimshawi has the lowest transposon density (particularly DINE-1: 2% vs. 11–27%). F element genes have larger coding spans, more coding exons, larger introns, and lower codon bias. Comparison of the Effective Number of Codons with the Codon Adaptation Index shows that, in contrast to the other species, codon bias in D. grimshawi F element genes can be attributed primarily to selection instead of mutational biases, suggesting that density and types of transposons affect the degree of local heterochromatin formation. F element genes have lower estimated DNA melting temperatures than D element genes, potentially facilitating transcription through heterochromatin. Most F element genes (~90%) have remained on that element, but the F element has smaller syntenic blocks than genome averages (3.4–3.6 vs. 8.4–8.8 genes per block), indicating greater rates of inversion despite lower rates of recombination. Overall, the F element has maintained characteristics that are distinct from other autosomes in the Drosophila lineage, illuminating the constraints imposed by a heterochromatic milieu.

The neurobiological mechanisms of insomnia may involve altered patterns of activation across sleep-wake states in brain regions associated with cognition, self-referential processes, affect, and sleep-wake promotion. The objective of this study was to compare relative regional cerebral metabolic rate for glucose (rCMRglc) in these brain regions across wake and nonrapid eye movement (NREM) sleep states in patients with primary insomnia (PI) and good sleeper controls (GS). Participants included 44 PI and 40 GS matched for age (mean = 37 y old, range 21–60), sex, and race. We conducted [18F]fluoro-2-deoxy-d-glucose positron emission tomography scans in PI and GS during both morning wakefulness and NREM sleep at night. Repeated measures analysis of variance was used to test for group (PI vs. GS) by state (wake vs. NREM sleep) interactions in relative rCMRglc. Significant group-by-state interactions in relative rCMRglc were found in the precuneus/posterior cingulate cortex, left middle frontal gyrus, left inferior/superior parietal lobules, left lingual/fusiform/occipital gyri, and right lingual gyrus. All clusters were significant at Pcorrected < 0.05. Insomnia was characterized by regional alterations in relative glucose metabolism across NREM sleep and wakefulness. Significant group-by-state interactions in relative rCMRglc suggest that insomnia is associated with impaired disengagement of brain regions involved in cognition (left frontoparietal), self-referential processes (precuneus/posterior cingulate), and affect (left middle frontal, fusiform/lingual gyri) during NREM sleep, or alternatively, to impaired engagement of these regions during wakefulness. Kay DB, Karim HT, Soehner AM, Hasler BP, Wilckens KA, James JA, Aizenstein HJ, Price JC, Rosario BL, Kupfer DJ, Germain A, Hall MH, Franzen PL, Nofzinger EA, Buysse DJ. Sleep-wake differences in relative regional cerebral metabolic rate for glucose among patients with insomnia compared with good sleepers. SLEEP 2016;39(10):1779–1794.

Previous studies in late-life depression (LLD) have found that patients have altered intrinsic functional connectivity in the dorsal default mode network (DMN) and executive control network (ECN). We aimed to detect connectivity differences across a treatment trial among LLD patients as a function of remission status. LLD patients (N=37) were enrolled into a 12-week trial of venlafaxine and underwent five functional magnetic resonance imaging resting state scans during treatment. Patients had no history of drug abuse, psychosis, dementia/neurodegenerative diseases or medical conditions with known effects on mood. We investigated whether there were differences in three networks: DMN, ECN and anterior salience network connectivity, as well as a whole brain centrality measure (eigenvector centrality). We found that remitters showed increases in ECN connectivity in the right precentral gyrus and decreases in DMN connectivity in the right inferior frontal gyrus and supramarginal gyrus. The ECN and DMN had regions (middle temporal gyrus and bilateral middle/inferior temporal/fusiform gyrus, respectively) that showed reversed effects (decreased ECN and increased DMN, respectively). Early changes in functional connectivity can occur after initial medication exposure. This study offers new data, indicating that functional connectivity changes differ depending on treatment response and can occur shortly after exposure to antidepressant medication.