Association between Perceived Stress and Motoric Cognitive Risk Syndrome in an Elderly Population: Rugao Longevity and Aging Study.

INTRODUCTION: Previous studies have indicated a correlation between perceived stress and cognitive decline. However, it remains unknown whether high levels of perceived stress can result in motoric cognitive risk (MCR) syndrome. This study investigated the relationship between perceived stress and MCR in a community-based population. METHODS: The study cohort comprised 852 elderly individuals from the Rugao Longitudinal Aging Cohort. Perceived stress was assessed using the 10-item Perceived Stress Scale (PSS-10), while MCR was defined as the coexistence of subjective memory complaints (SMCs) and slow gait speed. RESULTS: The average age of the study participants is 79.84 ± 4.34 years. The mean score of PSS-10 among participants is 10.32 (range = 0-33; [SD] = 5.71), with a median score of 10.00 (6.00, 14.00). The prevalence of MCR is 9.3%. In the logistic regression analysis, for each 1-SD (5.71) increase in the global PSS-10 score, the risk of MCR increased by 40% (95% CI 1.09-1.80). Additionally, in the aspect of two components of MCR, with a 1-SD increase (5.71) in the global PSS-10 score, there was a 50% (95% CI 1.29-1.75) increase in the risk of SMCs and a 27% (95% CI 1.04-1.55) increase in the risk of slow gait speed. In terms of specific walking speed, there was a reverse correlation between the global PSS-10 score and walking speed (r = -0.14, p < 0.001). CONCLUSIONS: This study provided preliminary evidence that high levels of perceived stress were associated with the risk of MCR in a community-dwelling population.

The effect of processing speed on verbal and visual memory of adults with a chronic acquired brain injury.

OBJECTIVE: Memory problems are among the most frequently reported cognitive complaints by individuals with an acquired brain injury (ABI). Processing speed and working memory deficits are often the result of ABI. These cognitive deficits significantly impact the acquisition and retention of information necessary for memory formation. This study investigated the influence of processing speed and working memory on immediate and delayed recall for verbal and visual memory, as well as overall memory recall in adults living with a chronic ABI. METHODS: Sixty-three participants living with a chronic ABI, who were at least one-year post-injury, were cognitively assessed with the CNS-Vital Signs (CNS-VS) computerized cognitive battery and Wechsler Test of Adult Reading. RESULTS: The CNS-VS Processing Speed significantly predicted delayed recall for verbal memory and overall memory performance. The CNS-VS Working Memory was not a significant predictor of memory recall. CONCLUSIONS: Processing speed deficits negatively impact memory in individuals with a chronic ABI. These findings suggest the memory recall of adults with a chronic ABI is associated with poor processing speed and poor acquisition of information. Therefore, cognitive rehabilitation that improves processing speed should be the focus for individuals with ABI to improve memory performance as well as impaired processing speed.

Individual differences in frequency and impact of daily memory lapses: results from a national lifespan sample.

BACKGROUND: Everyday memory problems are believed to increase with age, leading many researchers to focus on older ages when examining reports of memory lapses. However, real world memory lapses are ubiquitous across the adult lifespan, though less is known about the types of problems and their impacts at younger ages. The current study examined occurrence and impacts of memory lapses using daily diaries in a broad age range and whether characteristics of lapses varied across age, gender, or education level. METHODS: Using an 8-day daily diary protocol, 2,018 individuals (ages 25-91) provided reports of their experiences of two types of daily memory lapses (retrospective and prospective) as well as the impact those lapses had on their emotional and functional well-being that day. Using multilevel modeling, we examined the likelihood of reporting memory lapses and their impacts on daily life and whether these depended on age, gender, or education level. RESULTS: Participants reported lapses on approximately 40% of days; retrospective memory lapses were significantly more likely than prospective lapses. Older ages and higher education level were related to greater likelihood of reporting retrospective lapses. Women (compared to men) were more likely to report prospective memory lapses. Women also tended to report greater impacts of their memory lapses. Lower education levels were related to greater impacts of memory lapses compared to higher education levels. Interestingly, age was not related to impacts of lapses. DISCUSSION: Our results indicate that memory lapses are common across the lifespan and that those individuals more likely to report lapses are not necessarily those that experience the greatest impacts of those lapses on daily life. Additional work is needed to understand the daily experience of memory lapses and how they differentially affect individuals regardless of age, gender, and education. CONCLUSIONS: Memory lapses are an important aspect of daily life across the lifespan and require measurement in an individual's real-world environments. Better measurement of these experiences will allow the development of more sensitive measures of changes in cognitive functioning that may impact an individual's ability to live independently.

Cognitive profile in functional disorders.

INTRODUCTION: Patients with functional disorders (FD) often experience cognitive problems such as forgetfulness and distractibility alongside physical symptoms that cannot be attributed to a known somatic disease. METHOD: Test scores of cognitive tests and psychiatric rating scales of 100 outpatients diagnosed with a functional disorder were compared to a control group (n = 300) of patients with other diagnoses and to test norms for the general population. RESULTS: Out of the 100 patients with functional disorders, 59 reported significant subjective cognitive symptoms. A moderate difference (d = 0.5-0.7) was found between the FD group mean and the population mean in processing speed tests, as well as in four psychiatric rating scales (depression, anxiety, phobias, somatisation) but there were no statistically significant differences in verbal and nonverbal reasoning or in logical memory. Somatisation and logical verbal memory scores were higher in the FD group compared to the control group. CONCLUSION: The findings of the study suggest that a decline in processing speed is a central feature in the cognitive profile of patients with functional disorders.

"Cinderella was attacked by the big bad wolf, but the police saved her": intrusions and confabulations on story recall in Korsakoff's syndrome and alcohol-related cognitive impairments.

BACKGROUND: The relation between confabulations and intrusions in patients with Korsakoff's syndrome (KS) and patients with alcohol-related cognitive impairments (ARCI) remains under debate. This study examines (1) differences in the production of confabulations and intrusions between patients with KS and ARCI, (2) whether an altered fairy tale induces more intrusions, and (3) whether different types of intrusions were significantly related to confabulations. METHODS: Twenty-three patients with KS and twenty-two patients with ARCI recalled three different types of stories: a novel story, a fairy tale, and a modified fairy tale. Different types of intrusions were correlated with confabulation measures. RESULTS: Patients with KS produced more intrusions in the modified fairy tale condition than patients with ARCI, but these were unrelated to confabulations. Only unrelated intrusions were related to provoked confabulations. CONCLUSIONS: The results of this study indicate that researchers and clinicians must be aware that in general, intrusions on memory tests should not be interpreted as confabulations. Especially spontaneous confabulations appear to be something completely different from intrusions on any type of story recall. When measuring confabulations it is crucial to use validated instruments.

Deconstructing spontaneous expressions of memory in dementia.

Dementia syndromes offer a unique opportunity to clarify some of the component processes of spontaneous expressions of memory proposed by the Barzykowski and Moulin model. By considering the model through the lens of memory disorders, I outline several important extensions to progress our understanding of these spontaneous cognitive phenomena.

Unexpected Role of Physiological Estrogen in Acute Stress-Induced Memory Deficits.

Stress may promote emotional and cognitive disturbances, which differ by sex. Adverse outcomes, including memory disturbances, are typically observed following chronic stress, but are now being recognized also after short events, including mass shootings, assault, or natural disasters, events that consist of concurrent multiple acute stresses (MAS). Prior work has established profound and enduring effects of MAS on memory in males. Here we examined the effects of MAS on female mice and probed the role of hormonal fluctuations during the estrous cycle on MAS-induced memory problems and the underlying brain network and cellular mechanisms. Female mice were impacted by MAS in an estrous cycle-dependent manner: MAS impaired hippocampus-dependent spatial memory in early-proestrous mice, characterized by high levels of estradiol, whereas memory of mice stressed during estrus (low estradiol) was spared. As spatial memory requires an intact dorsal hippocampal CA1, we examined synaptic integrity in mice stressed at different cycle phases and found a congruence of dendritic spine density and spatial memory deficits, with reduced spine density only in mice stressed during high estradiol cycle phases. Assessing MAS-induced activation of brain networks interconnected with hippocampus, we identified differential estrous cycle-dependent activation of memory- and stress-related regions, including the amygdala. Network analyses of the cross-correlation of fos expression among these regions uncovered functional connectivity that differentiated impaired mice from those not impaired by MAS. In conclusion, the estrous cycle modulates the impact of MAS on spatial memory, and fluctuating physiological levels of sex hormones may contribute to this effect.SIGNIFICANCE STATEMENT: Effects of stress on brain functions, including memory, are profound and sex-dependent. Acute stressors occurring simultaneously result in spatial memory impairments in males, but effects on females are unknown. Here we identified estrous cycle-dependent effects of such stresses on memory in females. Surprisingly, females with higher physiological estradiol experienced stress-induced memory impairment and a loss of underlying synapses. Memory- and stress-responsive brain regions interconnected with hippocampus were differentially activated across high and low estradiol mice, and predicted memory impairment. Thus, at functional, network, and cellular levels, physiological estradiol influences the effects of stress on memory in females, providing insight into mechanisms of prominent sex differences in stress-related memory disorders, such as post-traumatic stress disorder.

mTOR Attenuation with Rapamycin Reverses Neurovascular Uncoupling and Memory Deficits in Mice Modeling Alzheimer's Disease.

Vascular dysfunction is a universal feature of aging and decreased cerebral blood flow has been identified as an early event in the pathogenesis of Alzheimer's disease (AD). Cerebrovascular dysfunction in AD includes deficits in neurovascular coupling (NVC), a mechanism that ensures rapid delivery of energy substrates to active neurons through the blood supply. The mechanisms underlying NVC impairment in AD, however, are not well understood. We have previously shown that mechanistic/mammalian target of rapamycin (mTOR) drives cerebrovascular dysfunction in models of AD by reducing the activity of endothelial nitric oxide synthase (eNOS), and that attenuation of mTOR activity with rapamycin is sufficient to restore eNOS-dependent cerebrovascular function. Here we show mTOR drives NVC impairments in an AD model through the inhibition of neuronal NOS (nNOS)- and non-NOS-dependent components of NVC, and that mTOR attenuation with rapamycin is sufficient to restore NVC and even enhance it above WT responses. Restoration of NVC and concomitant reduction of cortical amyloid-ß levels effectively treated memory deficits in 12-month-old hAPP(J20) mice. These data indicate that mTOR is a critical driver of NVC dysfunction and underlies cognitive impairment in an AD model. Together with our previous findings, the present studies suggest that mTOR promotes cerebrovascular dysfunction in AD, which is associated with early disruption of nNOS activation, through its broad negative impact on nNOS as well as on non-NOS components of NVC. Our studies highlight the potential of mTOR attenuation as an efficacious treatment for AD and potentially other neurologic diseases of aging.SIGNIFICANCE STATEMENT Failure of the blood flow response to neuronal activation [neurovascular coupling (NVC)] in a model of AD precedes the onset of AD-like cognitive symptoms and is driven, to a large extent, by mammalian/mechanistic target of rapamycin (mTOR)-dependent inhibition of nitric oxide synthase activity. Our studies show that mTOR also drives AD-like failure of non-nitric oxide (NO)-mediated components of NVC. Thus, mTOR attenuation may serve to treat AD, where we find that neuronal NO synthase is profoundly reduced early in disease progression, and potentially other neurologic diseases of aging with cerebrovascular dysfunction as part of their etiology.

CD8+ T-Lymphocyte-Driven Limbic Encephalitis Results in Temporal Lobe Epilepsy.

OBJECTIVE: Limbic encephalitis (LE) comprises a spectrum of inflammatory changes in affected brain structures including the presence of autoantibodies and lymphoid cells. However, the potential of distinct lymphocyte subsets alone to elicit key clinicopathological sequelae of LE potentially inducing temporal lobe epilepsy (TLE) with chronic spontaneous seizures and hippocampal sclerosis (HS) is unresolved. METHODS: Here, we scrutinized pathogenic consequences emerging from CD8+ T cells targeting hippocampal neurons by recombinant adeno-associated virus-mediated expression of the model-autoantigen ovalbumin (OVA) in CA1 neurons of OT-I/RAG1-/- mice (termed "OVA-CD8+ LE model"). RESULTS: Viral-mediated antigen transfer caused dense CD8+ T cell infiltrates confined to the hippocampal formation starting on day 5 after virus transduction. Flow cytometry indicated priming of CD8+ T cells in brain-draining lymph nodes preceding hippocampal invasion. At the acute model stage, the inflammatory process was accompanied by frequent seizure activity and impairment of hippocampal memory skills. Magnetic resonance imaging scans at day 7 of the OVA-CD8+ LE model revealed hippocampal edema and blood-brain barrier disruption that converted into atrophy until day 40. CD8+ T cells specifically targeted OVA-expressing, SIINFEKL-H-2Kb -positive CA1 neurons and caused segmental apoptotic neurodegeneration, astrogliosis, and microglial activation. At the chronic model stage, mice exhibited spontaneous recurrent seizures and persisting memory deficits, and the sclerotic hippocampus was populated with CD8+ T cells escorted by NK cells. INTERPRETATION: These data indicate that a CD8+ T-cell-initiated attack of distinct hippocampal neurons is sufficient to induce LE converting into TLE-HS. Intriguingly, the role of CD8+ T cells exceeds neurotoxic effects and points to their major pathogenic role in TLE following LE. ANN NEUROL 2021;89:666-685.

Candesartan protects against d-galactose induced - Neurotoxicity and memory deficit via modulation of autophagy and oxidative stress.

PURPOSE: d-galactose induces neuroinflammation and memory deficit via oxidative stress. Candesartan is an angiotensin II-receptor blocker and has proved neuroprotective properties. This study aimed to investigate the neuroprotective effect of candesartan against d-galactose induced neuroinflammation and memory deficit via autophagy. METHODS: Twenty-eight male Wistar rats aged 3 months were divided into four equal groups: control (vehicle), d-gal (100 mg/kg d-galactose), cand (1 mg/kg candesartan), and cand+d-gal (100 mg/kg d-galactose & 1 mg/kg candesartan). All treatments were given orally and daily for 4 weeks. Assessment of memory was done using Morris water maze (MWM) test. Brain tissue was assessed for malondialdehyde (MDA), total thiol, catalase activity, glial fibrillary acidic protein (GFAP) and gene expression of TNF-α, GDNF-1 as well as autophagy genes (Beclin 1 and ATG 5). RESULTS: Prophylactic treatment of candesartan in d-galactose-treated rats significantly (p < 0.001) reduced oxidative stress via reduction of MDA as well as elevation of catalase activity and total thiol levels. Additionally, candesartan prophylactic treatment significantly increased gene expression of GDNF-1 and decreased gene expression of TNF-α. Furthermore, candesartan significantly increased the expression of autophagy related gene (Beclin 1 and ATG 5) in cand+d-gal treated rats. These results were supported by the histopathological findings which showed that candesartan prevented the neuronal injury in the cerebral cortex and hippocampus and decreased GFAP positive cells of the d-galactose-treated rats. Moreover, MWM test showed that candesartan significantly improved memory deficit in cand+d-gal treated rats. CONCLUSION: Candesartan prevents d-galactose-induced neurotoxicity and memory deficit via activating autophagy and decreasing oxidative stress. Therefore, candesartan was a good candidate for age-related neurodegenerative disorders and memory deficit.

Subjective Memory Complaints and Their Relationship with the Objective Cognitive Performance of Stroke Patients.

INTRODUCTION: Subjective memory complaints (SMCs) are common among patients with stroke, significantly affect long-term disability, and contribute to poor functional outcomes. We explored changes in the subjective memory complaints questionnaire (SMCQ) score of stroke patients, correlations among SMCs, objective cognitive performance (OCP), and functional status. We also explored whether participants could be divided into groups based on the presence or absence of SMCs and OCP impairment, which could be related to rehabilitation outcomes. METHODS: A total of 102 stroke patients were recruited from a single rehabilitation center. Their OCP was determined on admission. The Mini-Mental State Evaluation (MMSE), SMCQ, and modified Barthel Index (MBI) scores were obtained at admission and at discharge. These variables were compared and time and group interactions were explored. RESULTS: The SMCQ score did not show consistent patterns of change among individuals. The objective cognitive function and activities of daily living consistently improved after rehabilitation. The proposed cognitive impairment classification after stroke based on SMCs and objective cognitive decline was able to predict improvement attributable to rehabilitation. CONCLUSION: Changes in SMCQ scores of stroke patients were inconsistent and varied when compared to changes in MMSE and MBI scores, indicating that it is not a reliable metric on its own. SMCs have a clinical relationship with OCP and significant emotional and motivational effects. In clinical practice, it is important to understand and consider SMCs after stroke.

Accelerated Long-Term Forgetting: Prolonged Delayed Recognition as Sensitive Measurement for Different Profiles of Long-Term Memory and Metacognitive Confidence in Stroke Patients.

OBJECTIVE: Deficits in episodic memory are frequently reported after ischemic stroke. In standard clinical care, episodic memory is assessed after a 20-30 min delay, with abnormal memory decay over this period being characterized as rapid forgetting (RF). Previous studies have shown abnormal forgetting over a prolonged interval (days to weeks) despite normal acquisition, referred to as accelerated long-term forgetting (ALF). METHOD: We examined whether ALF is present in stroke patients (N = 91) using immediate testing (T1), testing after a short delay (20-30 min, T2), and testing after a prolonged delay (one week, T3). Based on performance compared to matched controls (N = 85), patients were divided into (1) patients without forgetting, (2) patients with RF between T1 and T2, and (3) patients with ALF at T3. Furthermore, confidence ratings were assessed. RESULTS: ALF was present in a moderate amount of stroke patients (17%), but ALF was even more prevalent in our stroke sample than RF after a 20-30 min delay (which was found in only 13% of our patients). Patients reported a lower confidence for their responses, independent of their actual performance. CONCLUSIONS: Adding a one-week delayed measurement may potentially assist in identifying patients with memory decrements that may otherwise go undetected.

Impaired Behavioral Pattern Separation in Refractory Temporal Lobe Epilepsy and Mild Cognitive Impairment.

OBJECTIVE: Episodic memory impairment and hippocampal pathology are hallmark features of both temporal lobe epilepsy (TLE) and amnestic mild cognitive impairment (aMCI). Pattern separation (PS), which enables the distinction between similar but unique experiences, is thought to contribute to successful encoding and retrieval of episodic memories. Impaired PS has been proposed as a potential mechanism underling episodic memory impairment in aMCI, but this association is less established in TLE. In this study, we examined behavioral PS in patients with TLE and explored whether profiles of performance in TLE are similar to aMCI. METHOD: Patients with TLE, aMCI, and age-matched, healthy controls (HCs) completed a modified recognition task that relies on PS for the discrimination of highly similar lure items, the Mnemonic Similarity Task (MST). Group differences were evaluated and relationships between clinical characteristics, California Verbal Learning Test-Second Edition scores, and MST performance were tested in the TLE group. RESULTS: Patients with TLE and aMCI demonstrated poorer PS performance relative to the HCs, but performance did not differ between the two patient groups. Neither the side of seizure focus nor having hippocampal sclerosis affected performance in TLE. However, TLE patients with clinically defined memory impairment showed the poorest performance. CONCLUSION: Memory performance on a task that relies on PS was disrupted to a similar extent in TLE and aMCI. The MST could provide a clinically useful tool for measuring hippocampus-dependent memory impairments in TLE and other neurological disorders associated with hippocampal damage.

Association of Being Accompanied at Medical Consultation and Having Memory Complaints With Cognitive Impairment in Elderly Brazilian Outpatients.

BACKGROUND: The usefulness of both the presence of a companion at the medical consultation and patient's cognitive complaints as selection strategies for performing a dementia evaluation is still unclear. OBJECTIVES: To estimate the association of elderly patients being accompanied during medical visits and patient's memory complaint with objective cognitive impairment. METHODS: We included elderly outpatients awaiting medical consultations in 3 non-neurological medical specialties. Demographic and Mini-Mental State Examination were collected. Patients' memory complaints were evaluated with a single question to both patients and companions. RESULTS: Five hundred ninety-three elderly patients were included in the study with 64.6% female and median (interquartile range) age 73 (68-78), 4 (2-6) years of education. Of these, 242 patients were accompanied and 62.6% presented memory complaints. The median (interquartile range) Mini-Mental State Examination scores were significantly lower in patients accompanied and in those with memory complaints. In a logistic regression model, age, education, memory complaint, and presence of companion were associated with cognitive impairment. In the model including only accompanied patients, only age and companion memory complaints were associated with objective cognitive impairment. CONCLUSIONS: The presence of a companion during a clinical consultation and patients' memory complaints are both synergistically associated with objective cognitive impairment.

The frequency and framing of cognitive lapses in healthy adults.

OBJECTIVE: Many people present to health services with concern about cognitive symptoms. In a significant proportion those symptoms are not the result of pathologically defined brain disease. In some they are part of a functional cognitive disorder (FCD). We assessed the frequency of cognitive lapses in a non-clinical sample in order to consider the utility of frequency of cognitive lapses in diagnosing cognitive disorders. METHODS: Healthy adults, who had never sought help for cognitive symptoms, completed a questionnaire, distributed via social media, about self-evaluation of cognitive function, frequency of cognitive lapses, and use of memory aids, including Schmitdke and Metternich's functional memory disorder (FMD) inventory. RESULTS: One hundred and twenty-four adults, aged 18-59 (median 23), most with further or higher education, responded. Thirty-one (25%) reported "fair" or "poor" memory. Forty-eight (39%) reported memory worse than 5 years ago, and 30 (24%) reported memory worse than others the same age. Participants endorsed a mean 13/18 specific cognitive lapses at least monthly. One hundred and eleven (89%) scored ≥4, the suggested cutoff for the FMD inventory. CONCLUSIONS: Cognitive lapses described in FCDs are common in highly educated adults. The high frequency of lapses in this healthy population suggests self-reported frequency of lapses alone cannot discriminate FCDs from "normal" experiences. Further research is required to clarify the role of abnormal metacognition in FCD. Better understanding of the factors moderating subjective interpretation of cognitive failures will also aid development of better clinical risk-stratification methods in people concerned about future dementia.

Age Differences In Retrieval-Related Reinstatement Reflect Age-Related Dedifferentiation At Encoding.

Age-related reductions in neural selectivity have been linked to cognitive decline. We examined whether age differences in the strength of retrieval-related cortical reinstatement could be explained by analogous differences in neural selectivity at encoding, and whether reinstatement was associated with memory performance in an age-dependent or an age-independent manner. Young and older adults underwent fMRI as they encoded words paired with images of faces or scenes. During a subsequent scanned memory test participants judged whether test words were studied or unstudied and, for words judged studied, also made a source memory judgment about the associated image category. Using multi-voxel pattern similarity analyses, we identified robust evidence for reduced scene reinstatement in older relative to younger adults. This decline was however largely explained by age differences in neural differentiation at encoding; moreover, a similar relationship between neural selectivity at encoding and retrieval was evident in young participants. The results suggest that, regardless of age, the selectivity with which events are neurally processed at the time of encoding can determine the strength of retrieval-related cortical reinstatement.

Cognitive Deficits and Clinical Symptoms with Hippocampal Subfields in First-Episode and Never-Treated Patients with Schizophrenia.

Memory dysfunction and associated hippocampal disturbances play crucial roles in cognitive impairment of schizophrenia. To examine the relationships between cognitive function and the hippocampal subfields (HSs) in first-episode never-treated (FENT) schizophrenia patients, the HSs were segmented in 39 FENT patients and 30 healthy controls using a state-of the-art automated algorithm. We found no significant differences in any HSs between the patients and controls. However, multivariate regression analysis showed that the left cornu ammonis 1 (CA1), left hippocampal tail, left presubiculum, and right molecular layer contributed 40% to the variance of the PANSS negative symptom score. After adjusting for sex, age, education, and intracranial volume, the partial correlation analysis showed that the volumes of left CA1, CA3, CA4, molecular layer, granule cell layer and both left and right subiculum were negatively correlated with the MATRICS consensus cognitive battery (MCCB) Hopkins Verbal Learning Test (HVLT). Multiple regression analysis showed that the left CA1 and CA3 hippocampal abnormalities contributed 66% to the variance of the HVLT. Our results suggest no detectable HS deficits were found in FENT schizophrenia patients. However, the HSs may be involved in the symptoms and cognitive deficits of schizophrenia patients in the early phase of their illness.

Poor Self-Reported Sleep is Related to Regional Cortical Thinning in Aging but not Memory Decline-Results From the Lifebrain Consortium.

We examined whether sleep quality and quantity are associated with cortical and memory changes in cognitively healthy participants across the adult lifespan. Associations between self-reported sleep parameters (Pittsburgh Sleep Quality Index, PSQI) and longitudinal cortical change were tested using five samples from the Lifebrain consortium (n = 2205, 4363 MRIs, 18-92 years). In additional analyses, we tested coherence with cell-specific gene expression maps from the Allen Human Brain Atlas, and relations to changes in memory performance. "PSQI # 1 Subjective sleep quality" and "PSQI #5 Sleep disturbances" were related to thinning of the right lateral temporal cortex, with lower quality and more disturbances being associated with faster thinning. The association with "PSQI #5 Sleep disturbances" emerged after 60 years, especially in regions with high expression of genes related to oligodendrocytes and S1 pyramidal neurons. None of the sleep scales were related to a longitudinal change in episodic memory function, suggesting that sleep-related cortical changes were independent of cognitive decline. The relationship to cortical brain change suggests that self-reported sleep parameters are relevant in lifespan studies, but small effect sizes indicate that self-reported sleep is not a good biomarker of general cortical degeneration in healthy older adults.

Association of alcohol use with memory decline in middle-aged and older Chinese: a longitudinal cohort study.

BACKGROUND: Previous studies on associations of alcohol use with memory decline showed inconclusive results. We examined these associations using longitudinal data from the Guangzhou Biobank Cohort Study (GBCS) and explored whether these associations varied by sex and age group. METHODS: Memory function was assessed by delayed 10-word recall test (DWRT) and immediate 10-word recall test (IWRT) at both baseline (2003-2008) and follow-up (2008-2012) examinations, expressed as the mean annual change and mean annual rate of change in scores. Memory cognitive impairment was defined by DWRT scores of less than 4. Multivariable linear regression models and restricted cubic spline were used for data analysis. RESULTS: Of 14,827 participants without memory cognitive impairment at baseline, 90.2% were never or occasional drinkers, 5% moderate drinkers, 1.5% excessive drinkers, and 3.3% former drinkers. The mean (standard deviation) age was 60.6 (6.6) years old. During an average of 4.1 years follow-up, 1000 (6.7%) participants developed memory cognitive impairment. After adjusting for confounders, compared with never or occasional drinkers, moderate and excessive drinkers had significant decline in DWRT scores (ß, 95% confidence interval (CI) = -0.04 (-0.08 to -0.01), and - 0.07 (-0.14 to 0.01), respectively), and IWRT scores (ß, 95% CI = -0.10 (-0.19 to -0.01), and - 0.15 (-0.30 to 0.01), respectively) annually. With respect to the mean annual rate of change, moderate and excessive drinkers also showed greater decline in DWRT scores (ß, 95% CI = -1.02% (-1.87% to -0.16%), and - 1.64% (-3.14% to -0.14%), respectively). The associations did not vary by sex and age group (all P values for interaction ≥ 0.10). CONCLUSION: Compared to never or occasional alcohol use, moderate and excessive alcohol users had greater memory decline and the associations did not vary by sex and age group.

Endogenous retroviruses are associated with hippocampus-based memory impairment.

Retrotransposons compose a staggering 40% of the mammalian genome. Among them, endogenous retroviruses (ERV) represent sequences that closely resemble the proviruses created from exogenous retroviral infection. ERVs make up 8 to 10% of human and mouse genomes and range from evolutionarily ancient sequences to recent acquisitions. Studies in Drosophila have provided a causal link between genomic retroviral elements and cognitive decline; however, in mammals, the role of ERVs in learning and memory remains unclear. Here we studied 2 independent murine models for ERV activation: muMT strain (lacking B cells and antibody production) and intracerebroventricular injection of streptozotocin (ICVI-STZ). We conducted behavioral assessments (contextual fear memory and spatial learning), as well as gene and protein analysis (RNA sequencing, PCR, immunohistochemistry, and western blot assays). Mice lacking mitochondrial antiviral-signaling protein (MAVS) and mice lacking stimulator of IFN genes protein (STING), 2 downstream sensors of ERV activation, provided confirmation of ERV impact. We found that muMT mice and ICVI-STZ mice induced hippocampal ERV activation, as shown by increased gene and protein expression of the Gag sequence of the transposable element intracisternal A-particle. ERV activation was accompanied by significant hippocampus-related memory impairment in both models. Notably, the deficiency of the MAVS pathway was protective against ICVI-STZ-induced cognitive pathology. Overall, our results demonstrate that ERV activation is associated with cognitive impairment in mice. Moreover, they provide a molecular target for strategies aimed at attenuating retroviral element sensing, via MAVS, to treat dementia and neuropsychiatric disorders.