Feasibility and Preliminary Efficacy of American Elderberry Juice for Improving Cognition and Inflammation in Patients with Mild Cognitive Impairment.

Despite data showing that nutritional interventions high in antioxidant/anti-inflammatory properties (anthocyanin-rich foods, such as blueberries/elderberries) may decrease risk of memory loss and cognitive decline, evidence for such effects in mild cognitive impairment (MCI) is limited. This study examined preliminary effects of American elderberry (Sambucus nigra subsp. canadensis) juice on cognition and inflammatory markers in patients with MCI. In a randomized, double-blind, placebo-controlled trial, patients with MCI (n = 24, Mage = 76.33 ± 6.95) received American elderberry (n = 11) or placebo (n = 13) juice (5 mL orally 3 times a day) for 6 months. At baseline, 3 months, and 6 months, patients completed tasks measuring global cognition, verbal memory, language, visuospatial cognitive flexibility/problem solving, and memory. A subsample (n = 12, 7 elderberry/5 placebo) provided blood samples to measure serum inflammatory markers. Multilevel models examined effects of the condition (elderberry/placebo), time (baseline/3 months/6 months), and condition by time interactions on cognition/inflammation outcomes. Attrition rates for elderberry (18%) and placebo (15%) conditions were fairly low. The dosage compliance (elderberry-97%; placebo-97%) and completion of cognitive (elderberry-88%; placebo-87%) and blood-based (elderberry-100%; placebo-100%) assessments was high. Elderberry (not placebo) trended (p = 0.09) towards faster visuospatial problem solving performance from baseline to 6 months. For the elderberry condition, there were significant or significantly trending decreases over time across several markers of low-grade peripheral inflammation, including vasorin, prenylcysteine oxidase 1, and complement Factor D. Only one inflammatory marker showed an increase over time (alpha-2-macroglobin). In contrast, for the placebo, several inflammatory marker levels increased across time (L-lactate dehydrogenase B chain, complement Factor D), with one showing deceased levels over time (L-lactate dehydrogenase A chain). Daily elderberry juice consumption in patients with MCI is feasible and well tolerated and may provide some benefit to visuospatial cognitive flexibility. Preliminary findings suggest elderberry juice may reduce low-grade inflammation compared to a placebo-control. These promising findings support the need for larger, more definitive prospective studies with longer follow-ups to better understand mechanisms of action and the clinical utility of elderberries for potentially mitigating cognitive decline.

Sex as a moderator of the sleep and cognition relationship in middle-aged and older adults: A preliminary investigation.

OBJECTIVES: Despite known sex differences in the prevalence of sleep disturbance and cognitive impairment, research investigating sex differences in sleep/cognition associations is limited. We examined sex as a moderator of associations between self-reported sleep and objective cognition in middle-aged/older adults. METHODS: Adults aged 50+ (32 men/31 women, Mage = 63.6 ± 7.7) completed the Pittsburgh Sleep Quality Index (PSQI) and cognitive tasks: Stroop (processing speed, inhibition), Posner (spatial attentional orienting) and Sternberg (working memory). Multiple regressions examined whether PSQI metrics (global score, sleep quality ratings, sleep duration, sleep efficiency) were independently or interactively (with sex) associated with cognition, controlling for age and education. RESULTS: Sex interacted with sleep quality ratings in its association with endogenous spatial attentional orienting (∆R2 = .10, p = .01). Worse ratings of sleep quality were associated with worse orienting in women (B = 22.73, SE = 9.53, p = .02), not men (p = .24). Sex interacted with sleep efficiency in its associations with processing speed (∆R2 = .06, p = .04). Lower sleep efficiency was associated with slower Stroop control trial performance in women (B = -15.91, SE = 7.57, p = .04), not men (p = .48). CONCLUSIONS: Preliminary findings suggest middle-aged/older women are more vulnerable to associations between poor sleep quality and low sleep efficiency on spatial attentional orienting and processing speed, respectively. Future studies in larger samples investigating sex-specific prospective sleep and cognition associations are warranted.

The Relation Between Attention and Memory.

The relation between attention and memory has long been deemed important for understanding cognition, and it was heavily researched even in the first experimental psychology laboratory by Wilhelm Wundt and his colleagues. Since then, the importance of the relation between attention and memory has been explored in myriad subdisciplines of psychology, and we incorporate a wide range of these diverse fields. Here, we examine some of the practical consequences of this relation and summarize work with various methodologies relating attention to memory in the fields of working memory, long-term memory, individual differences, life-span development, typical brain function, and neuropsychological conditions. We point out strengths and unanswered questions for our own embedded processes view of information processing, which is used to organize a large body of evidence. Last, we briefly consider the relation of the evidence to a range of other theoretical views before drawing conclusions about the state of the field.

Sleep characteristics and pain in middle-aged and older adults: Sex-specific impact of physical and sitting activity.

OBJECTIVES: The relationship between poor sleep health and worse pain is established. Physical activity has been successful in reducing chronic pain and improving sleep in aging adults. Despite known sex differences (more women than men experiencing chronic pain and insomnia), sex-specific patterns of interactive associations between physical activity, sleep, and pain remain unexplored. This study tested whether physical and sitting activity moderated associations between sleep characteristics and pain intensity, and whether sex further moderated these relationships. METHODS: Participants aged 50+ (N = 170, Mage = 64.34, 72 women) completed an online survey measuring pre-sleep arousal (Pre-sleep Arousal Scale), sleep (Pittsburgh Sleep Quality Index), past month average pain intensity, and physical activity (International Physical Activity Questionnaire). Multiple regressions evaluated whether minutes of physical activity (total, vigorous, moderate, walking) or sitting activity, pre-sleep arousal, sleep, sex, or their interaction was associated with pain. Analyses controlled for education, difficulty walking, body mass index, total medical conditions, pain medication, and depressive/anxiety symptoms. RESULTS: In women, vigorous activity interacted with total pre-sleep arousal and somatic pre-sleep arousal in its association with pain. Higher total arousal and somatic arousal were associated with worse pain intensity only for women who reported highest levels of vigorous activity. No such associations were observed for men or for other physical or sitting activity levels. CONCLUSIONS: Vigorous physical activity may exacerbate the association between more pre-sleep arousal and worse pain in middle-aged and older women. Research should explore potential sex-specific mechanisms (e.g., inflammatory cytokines, arousal neural networks) underlying these results.

The Relationship between Maternal Antibodies to Fetal Brain and Prenatal Stress Exposure in Autism Spectrum Disorder.

Environmental and genetic factors contribute to the etiology of autism spectrum disorder (ASD), but their interaction is less well understood. Mothers that are genetically more stress-susceptible have been found to be at increased risk of having a child with ASD after exposure to stress during pregnancy. Additionally, the presence of maternal antibodies for the fetal brain is associated with a diagnosis of ASD in children. However, the relationship between prenatal stress exposure and maternal antibodies in the mothers of children diagnosed with ASD has not yet been addressed. This exploratory study examined the association of maternal antibody response with prenatal stress and a diagnosis of ASD in children. Blood samples from 53 mothers with at least one child diagnosed with ASD were examined by ELISA. Maternal antibody presence, perceived stress levels during pregnancy (high or low), and maternal 5-HTTLPR polymorphisms were examined for their interrelationship in ASD. While high incidences of prenatal stress and maternal antibodies were found in the sample, they were not associated with each other (p = 0.709, Cramér's V = 0.051). Furthermore, the results revealed no significant association between maternal antibody presence and the interaction between 5-HTTLPR genotype and stress (p = 0.729, Cramér's V = 0.157). Prenatal stress was not found to be associated with the presence of maternal antibodies in the context of ASD, at least in this initial exploratory sample. Despite the known relationship between stress and changes in immune function, these results suggest that prenatal stress and immune dysregulation are independently associated with a diagnosis of ASD in this study population, rather than acting through a convergent mechanism. However, this would need to be confirmed in a larger sample.

Sex-Specific Contributions of Alcohol and Hypertension on Everyday Cognition in Middle-Aged and Older Adults.

Background: Separate lines of research have linked hypertension and alcohol use disorder to cognition among adults. Despite known sex differences in both of these conditions, studies examining associations on cognition are limited. We aimed to determine whether hypertension impacts the relationship between alcohol use and everyday subjective cognition and whether sex moderates this relationship in middle-aged and older adults. Materials and Methods: Participants (N = 275) 50+ years of age, who reported drinking, completed surveys measuring alcohol use (Alcohol Use Disorder Identification Test consumption items), self-reported history of hypertension, and everyday subjective cognition (Cognitive Failures Questionnaire [CFQ]). Regression was used to test a moderated moderation model examining independent and interactive roles of alcohol use, hypertension, and sex on cognition (CFQ scores: total, memory, distractibility, blunders, and names). Analyses controlled for age, years of education, race, body mass index, smoking status, depressive symptoms, global subjective sleep quality, number of prescription medication used, and number of comorbid medical conditions. Results: Sex moderated the interactive associations of hypertension and alcohol use frequency on CFQ-distractibility. Specifically, in women with hypertension, more alcohol use was associated with greater CFQ-distractibility (B = 0.96, SE = 0.34, p = 0.005). Discussion: Sex moderates the interactive association of hypertension and alcohol use on some aspects of subjective cognition in mid-to-late life. In women with hypertension, alcohol use may exacerbate problems with attentional control. Further exploration of sex- and or gender-specific mechanisms underlying these is warranted.

Pilot Study of the Effects of Paced Breathing on Measures of Convergent and Divergent Thinking.

BACKGROUND: The ability of the autonomic nervous system's stress response to impair aspects of cognitive flexibility is known. However, the ability to modulate the sympathetic response and improve these cognitive impairments via nonpharmacological intervention, such as paced breathing (PB), requires further investigation. OBJECTIVE: To better elucidate the effects of PB on cognition. METHOD: We employed a PB protocol in a total of 52 healthy men and women and measured performance on convergent and divergent cognitive tasks, perceived stress, and physiological measures (eg, blood pressure, heart rate). Participants attended two experimental sessions consisting of either PB or normal breathing followed by cognitive assessments including convergent (compound remote associate, anagram) and divergent (alternate use, fluency) tasks. Experiment 2 consisted of more difficult versions of cognitive tasks compared with Experiment 1. RESULTS: In Experiment 1, PB significantly reduced the female participants' systolic and diastolic blood pressure immediately after the breathing protocol without affecting their cognition. In Experiment 2, PB significantly reduced perceived stress immediately after the breathing protocol, regardless of sex. There was no effect on cognition in Experiment 2, but a correlation was observed between perceived stress change and anagram number solved change. CONCLUSION: While PB modulates sympathetic activity in females, there was a lack of improvement in cognitive flexibility performance. At least for a single trial of PB, cognitive flexibility did not improve.

Discrepancies in Objective and Subjective Cognition in Middle-Aged and Older Adults: Does Personality Matter?

Associations between subjective cognition and current objective functioning are inconclusive. Given known associations between personality and cognition, this study tested whether personality moderates associations between subjective memory and objective cognition in middle-aged and older adults. Participants (N = 62, M age = 63.8, SD = 7.7, 33 men) completed assessments of personality (Big Five Inventory-10), subjective memory (Cognitive Failures Questionnaire [CFQ-memory]), and objective cognition (processing speed, attention, inhibition [Stroop], working memory [Sternberg], set-shifting [Wisconsin Card Sorting Task]). Multiple regressions and simple slopes analyses examined whether personality moderates associations between subjective memory and objective cognition, controlling for age, number of medical conditions, and household income. Extraversion moderated associations between processing speed and CFQ-memory. Agreeableness moderated associations between set-shifting and CFQ-memory. Among individuals with higher extraversion and lower agreeableness, objectively worse cognition was associated with the fewest memory complaints. Findings suggest personality may impact the discrepancies between subjective memory and objective cognition in mid-to-late life.

Self-reported cognition in older adults with insomnia: Associations with sleep and domain specific cognition.

Poor subjective evaluation of cognition and sleep are associated with cognitive decline in older adults. Relationships among self-reported cognition, sleep, and cognitive domains remain unclear. We evaluated the interactive associations of objective cognition and subjective sleep with self-reported cognition in older adults with insomnia. Fifty-one older adults (Mage  = 69.19, SD = 7.95) with insomnia completed 14 days of self-reported cognition ratings (0-very poor, 100-very good), sleep (total sleep time (TST), sleep onset latency (SOL), wake after sleep onset (WASO), sleep efficiency), and daily cognitive tasks: Letter series (reasoning), word list delayed recall (verbal memory), Symbol Digit Modalities Test (SDMT) (attention/processing speed), and number copy (processing speed). Multiple regressions for each cognitive task determined whether average objective cognition or sleep were independently/interactively associated with average self-reported cognition, controlling for age, education, and depression. The interaction between SDMT performance and TST was associated with self-reported cognition. Specifically, the relationship between scores and self-reported cognition was congruent in those with the shortest TST. Similarly, the interactions between SDMT and WASO, as well as sleep efficiency, were associated with self-reported. Specifically, the relationship between scores and self-reported cognition was congruent in those with longest and average WASO, as well as shortest and average sleep efficiency. The findings suggest, in an older adult population with insomnia, a congruent association exists between attention/processing speed and self-reported cognition in those with worse subjective sleep (shorter TST, longer WASO, and lower SE). Insomnia symptoms should be taken into consideration when examining the relationship between objective cognition and self-reported cognition.

Sex differences in associations between alcohol use and sleep in mid-to-late life.

OBJECTIVES: To examine associations between alcohol use and sleep in middled-aged/older adults and to test sex as a moderator of this relationship. METHODS: Participants were 183 adults (46% female) ages 50 and above who consumed alcohol in the past year. Linear regressions tested sex as a moderator of associations between alcohol use and sleep parameters. Alcohol use was measured using the Alcohol Use Disorders Identification Test (AUDIT). Overall sleep health and sleep quality were assessed using the Pittsburgh Sleep Quality Index (PSQI), and pre-sleep arousal was assessed using the Pre-Sleep Arousal Scale. RESULTS: Overall, 11% of participants screened positive for hazardous drinking (AUDIT scores of 7+/8+ for women/men), and 59% reported poor overall sleep health (scores >5 on the PSQI). Alcohol use was not associated with overall sleep health (B = -0.25, p = .08) or pre-sleep arousal (B = 0.15, p = .64). However, contrary to hypotheses, more hazardous drinking was associated with better subjective sleep quality, only among women (B = -0.08, p = .009). Alcohol use was not associated with sleep quality among men (B = 0.01, p = .58). Associations remained significant when controlling for age, symptoms of anxiety and depression, body mass index, use of sleep medication, number of medical conditions, and chronic pain. CONCLUSIONS: Among middle-aged and older adults, alcohol use is more strongly associated with sleep patterns among women than men, when assessed concurrently (i.e., at the same time point). Findings support the need for further consideration of sex differences in associations between alcohol use and sleep.

Paradoxical relationship between subjective and objective cognition: the role of sleep.

STUDY OBJECTIVES: Subjective memory complaints and objective cognitive dysfunction are common in aging populations; however, research investigating the associations between them is inconclusive. Given the high prevalence of sleep complaints in middle-aged/older adults, this research tested whether objective cognition interacted with sleep parameters in its associations with subjective cognition. METHODS: Cognitively healthy adults aged 50+ years completed the Pittsburgh Sleep Quality Index, Cognitive Failures Questionnaire, and cognitive tasks: Stroop, Sternberg, and Posner cueing. Multiple regression and simple slope analyses examined whether objective cognition interacted with sleep parameters in its associations with subjective memory. RESULTS: Stroop performance and sleep (efficiency and disturbances) had interactive associations with Cognitive Failures Questionnaire-memory. Specifically, better Stroop performance (faster reaction time-control trials) was associated with more memory complaints at worst and average but not best sleep efficiency. Additionally, faster reaction time was associated with more memory complaints only for worst sleep disturbance. Similarly, Sternberg performance and sleep (efficiency and disturbances) had interactive associations with Cognitive Failures Questionnaire-memory. Specifically, higher proportion correct was associated with more memory complaints only at worst sleep efficiency and sleep disturbance. Finally, Posner performance and sleep disturbance had an interactive association with Cognitive Failures Questionnaire-memory. Faster exogenous orienting was associated with more memory complaints only for worst sleep disturbance. CONCLUSIONS: Objective cognition interacts with sleep efficiency and sleep disturbances in its associations with subjective memory in mid-to-late life. Findings suggest sleep fragmentation plays a role in the discrepant relationship between objective and subjective cognition. Future studies should investigate this relationship in aging populations with sleep disorders and/or cognitive impairments. CITATION: Costa AN, McCrae CS, Cowan N, Curtis AF. Paradoxical relationship between subjective and objective cognition: the role of sleep. J Clin Sleep Med. 2022;18(8):2009-2022.