Episodic Memory Loss Research Articles

Why does invasive brain stimulation sometimes improve memory and sometimes impair it?

Invasive brain stimulation is used to treat individuals with episodic memory loss; however, studies to date report both enhancement and impairment of memory. This Essay discusses the sources of this variability, and suggests a path towards developing customized stimulation protocols for more consistent memory enhancement.

Risk profiles of elite breath-hold divers

ABSTRACT This study aimed to determine a typical profile of elite breath-hold divers (BHDs), in relation to loss of consciousness (LOC) and episodic memory. Forty-four BHDs were evaluated during a world championship with anthropometric and physiological measurements, psychosociological factors and memory assessment. Seventy-five percent of the BHDs had at least one LOC with the predominance being men (p < 0.05). Thirty six percent of BHDs presented a low-risk profile and 64% a high-risk profile with no particular psychological pattern. Stepwise multiple linear regression showed that body fat, years of BH practice, age and forced vital capacity explained a significant amount of the variance of LOC for all BHDs (F(4,39) = 16.03, p < 0.001, R2 = 0.622, R2 Adjusted = 0.583). No correlation was found between resting physiological parameters and their training or depth performances. In conclusion, anthropometric data, pulmonary factors and breath-holding experience were predictive of LOC in elite BHDs, with men taking more risks. BHDs episodic memory was not impaired.

Atypical clinical variants of Alzheimer's disease: are they really atypical?

Alzheimer's disease (AD) is a neuropathological disorder defined by the deposition of the proteins, tau and β-amyloid. Alzheimer's disease is commonly thought of as a disease of the elderly that is associated with episodic memory loss. However, the very first patient described with AD was in her 50's with impairments in multiple cognitive domains. It is now clear that AD can present with multiple different non-amnestic clinical variants which have been labeled as atypical variants of AD. Instead of these variants of AD being considered "atypical," I propose that they provide an excellent disease model of AD and reflect the true clinical heterogeneity of AD. The atypical variants of AD usually have a relatively young age at onset, and they show striking cortical tau deposition on molecular PET imaging which relates strongly with patterns of neurodegeneration and clinical outcomes. In contrast, elderly patients with AD show less tau deposition on PET, and neuroimaging and clinical outcomes are confounded by other age-related pathologies, including TDP-43 and vascular pathology. There is also considerable clinical and anatomical heterogeneity across atypical and young-onset amnestic variants of AD which reflects the fact that AD is a disease that causes impairments in multiple cognitive domains. Future studies should focus on careful characterization of cognitive impairment in AD and consider the full clinical spectrum of AD, including atypical AD, in the design of research studies investigating disease mechanisms in AD and clinical treatment trials, particularly with therapeutics targeting tau.

Caution to Poor Adherence With Immunosuppressant Medication That Causes Coma-Onset Autoimmune Encephalitis: A Case Report and Literature Review

Autoimmune encephalitis after liver transplantation (LT) is a rare disorder. This is because patients are usually in an immunosuppressed state after LT. Here, we report a rare case of autoantibody-negative autoimmune-encephalitis-induced coma after living-donor (LD) LT. A 45-year-old woman who underwent LDLT for primary biliary cholangitis (PBC) was brought to our hospital with the chief complaint of cognitive deficiency and an episode of memory loss. Physical examination, laboratory tests, and cerebrospinal fluid analysis revealed no significant findings. However, diffusion-weighted magnetic resonance imaging showed hyperintensity in the bilateral hippocampus. No autoantibodies associated with autoimmune encephalitis were detected. The diagnosis of antibody-negative autoimmune encephalitis was made on the basis of low immunosuppressive drug levels in the blood (indicative of poor adherence) and the presence of PBC as the autoimmune disease. The patient regained consciousness after intravenous methylprednisolone pulse therapy and plasma exchange. This case highlights that when examining patients with impaired consciousness after LDLT, it is important to consider autoimmune encephalitis as a potential diagnosis.

Stimulus material selection for the Dutch famous faces test for older adults.

Worldwide, approximately 22% of all individuals aged 50 years and older are currently estimated to fall somewhere on the Alzheimer's disease (AD) continuum, which can be roughly divided into preclinical AD, mild cognitive impairment (MCI), and AD dementia. While episodic memory loss (among other aspects) is typically required for a diagnosis of AD dementia, MCI is said to have occurred when cognitive impairment (including memory loss) is worse than expected for the person's age but not enough to be classified as dementia. On the other hand, preclinical AD can currently only be detected using biomarkers; clinical symptoms are not apparent using traditional neuropsychological tests. The main aim of the current paper was to explore the possibility of a test which could distinguish preclinical AD from normal aging. Recent scientific evidence suggests that the Famous Faces Test (FFT) could differentiate preclinical AD from normal aging up to 5 years before a clinical AD diagnosis. Problematic with existing FFTs is the selection of stimulus material. Faces famous in a specific country and a specific decade might not be equally famous for individuals in another country or indeed for people of different ages. The current article describes how famous faces were systematically selected and chosen for the Dutch older (60+) population using five steps. The goal was to design and develop short versions of the FFT for Dutch older adults of equivalent mean difficulty. In future work, these nine parallel versions will be necessary for (a) cross-sectional comparison as well as subsequent longitudinal assessment of cognitively normal and clinical groups and (b) creating personalized norms for the normal aged controls that could be used to compare performance within individuals with clinical diagnoses. The field needs a simple, cognitive test which can distinguish the earliest stages of the dementia continuum from normal aging.

Concordance Between Logical Memory and Craft Story 21 in Community-Dwelling Older Adults: The Role of Demographic Factors And Cognitive Status.

Episodic memory loss, a hallmark symptom of Alzheimer's Disease, is frequently quantified by story memory performance. The National Alzheimer's Coordinating Center Uniform Data Set Neuropsychological Battery (UDSNB) replaced Logical Memory with Craft Story 21 in UDSNB Version 3. The concordance between these story memory tasks is poorly characterized in demographically diverse older adults, possibly jeopardizing the integrity of longitudinal data in aging cohorts. Einstein Aging Study participants (n = 298; Mage = 76.6; Meducation = 15; 66.4% women; 43.3% Non-Hispanic White) completed UDSNB measures, including Craft Story and Logical Memory. Classification as normal cognition (n = 206) or mild cognitive impairment (n = 90) was based on Jak/Bondi criteria. Analyses included correlations, linear regression, and equipercentile equating methods to characterize the relationship between Logical Memory and Craft Story. Multivariate linear mixed effects models explored the association of covariates and practice effects over follow-up, stratified by cognitive status and race/ethnicity. Immediate (r = 0.54) and delayed (r = 0.56) versions of Logical Memory and Craft Story were moderately correlated. Age, education, depression, and female sex were associated with Logical Memory, while age, education, cognitive status, and male sex were associated with Craft Story. Significant differential effects of sex on story memory were observed. We demonstrated that Logical Memory and Craft Story may be used largely interchangeably; however, memory may be enhanced for stories with a protagonist of the same sex as the participant. Craft Story was somewhat more associated with mild cognitive impairment in the overall sample, but especially in non-Hispanic Black participants. We discuss how results inform test selection considerations.

Neuropsychiatric, cognitive and sexual impairment in mastocytosis patients

BackgroundMastocytosis is a rare disease characterised by the accumulation and/or proliferation of abnormal mast cells (MCs) in one or several organs. It may present with a number of different symptoms that involve various organ systems. The current study aims to assess the prevalence of MC mediator-related symptoms in a cohort of mastocytosis patients with a specific focus on neurological, psychiatric, cognitive and sexual symptoms. We also assessed the impact of the disease on patients’ professional lives. Patients were administered a validated multidimensional questionnaire to collect information on patients’ perception of the severity of their symptoms. From the questionnaires we extracted the neurological, cognitive, psychiatric and sexual symptoms and the impact of the disease on patients’ professional lives as well as their grading. The affective status was assessed using the 17-item version of the Hamilton Depression Rating Scale.ResultsWe included 139 patients. Mastocytosis was classified as systemic in 113 patients and cutaneous in 26 patients. The prevalence of MC mediator-related systemic symptoms was as follows: cutaneous (71%), gastro-intestinal (48%), cardio-vascular (36%), musculoskeletal (26.6%), fatigue (24%), urinary (14.4%) and respiratory (10%). Headaches and vertigo were noted in respectively 55% and 32% of patients. Irritability, episodes of memory loss and difficulty concentrating were reported in 54%, 52% and 40% of cases, respectively. Sexual impairment was noted in 24% of patients. No associations were found between neuropsychiatric/cognitive impairment and age, gender, diagnostic delay, disease form, the presence of cutaneous lesions, the level of serum and bone marrow tryptase and the presence of KIT mutation in bone marrow and/or skin. Depression was noted in 49% of patients. One in four patients reported a negative impact of the disease on their professional lives.ConclusionThis current study provides some insights regarding symptoms related to mastocytosis and their impact on patients’ professional lives.

Oh brother, where art tau? Amyloid, neurodegeneration, and cognitive decline without elevated tau

Mild cognitive impairment (MCI) can be an early manifestation of Alzheimer’s disease (AD) pathology, other pathologic entities [e.g., cerebrovascular disease, Lewy body disease, LATE (limbic-predominant age-related TDP-43 encephalopathy)], or mixed pathologies, with concomitant AD- and non-AD pathology being particularly common, albeit difficult to identify, in living MCI patients. The National Institute on Aging and Alzheimer’s Association (NIA-AA) A/T/(N) [β-Amyloid/Tau/(Neurodegeneration)] AD research framework, which classifies research participants according to three binary biomarkers [β-amyloid (A+/A-), tau (T+/T-), and neurodegeneration (N+/N-)], provides an indirect means of identifying such cases. Individuals with A+T-(N+) MCI are thought to have both AD pathologic change, given the presence of β-amyloid, and non-AD pathophysiology, given neurodegeneration without tau, because in typical AD it is tau accumulation that is most tightly linked to neuronal injury and cognitive decline. Thus, in A+T-(N+) MCI (hereafter referred to as “mismatch MCI” for the tau-neurodegeneration mismatch), non-AD pathology is hypothesized to drive neurodegeneration and symptoms, because β-amyloid, in the absence of tau, likely reflects a preclinical stage of AD. We compared a group of individuals with mismatch MCI to groups with A+T+(N+) MCI (or “prodromal AD”) and A-T-(N+) MCI (or “neurodegeneration-only MCI”) on cross-sectional and longitudinal cognition and neuroimaging characteristics. β-amyloid and tau status were determined by CSF assays, while neurodegeneration status was based on hippocampal volume on MRI. Overall, mismatch MCI was less “AD-like” than prodromal AD and generally, with some exceptions, more closely resembled the neurodegeneration-only group. At baseline, mismatch MCI had less episodic memory loss compared to prodromal AD. Longitudinally, mismatch MCI declined more slowly than prodromal AD across all included cognitive domains, while mismatch MCI and neurodegeneration-only MCI declined at comparable rates. Prodromal AD had smaller baseline posterior hippocampal volume than mismatch MCI, and whole brain analyses demonstrated cortical thinning that was widespread in prodromal AD but largely restricted to the medial temporal lobes (MTLs) for the mismatch and neurodegeneration-only MCI groups. Longitudinally, mismatch MCI had slower rates of volume loss than prodromal AD throughout the MTLs. Differences in cross-sectional and longitudinal cognitive and neuroimaging measures between mismatch MCI and prodromal AD may reflect disparate underlying pathologic processes, with the mismatch group potentially being driven by non-AD pathologies on a background of largely preclinical AD. These findings suggest that β-amyloid status alone in MCI may not reveal the underlying driver of symptoms with important implications for enrollment in clinical trials and prognosis.

Depression accelerates longitudinal progression of hippocampal atrophy and cognitive decline in preclinical Alzheimer’s disease

AbstractBackgroundAlthough depression is very common in the preclinical stage of Alzheimer’s disease (AD), it is still unclear whether depression moderates the progression of AD or not. In the present study, we aimed to investigate the moderation of depression on the relationship between β‐amyloid (Aβ) deposition and progression of hippocampal atrophy and cognitive decline in cognitively normal (CN) older adults.MethodTwo‐hundred eighty nine CN older adults (55–90 years; 48.4% female; 14.2% Aβ+) from an ongoing prospective cohort study, the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer’s Disease (KBASE), were followed up for 24 months. All participants underwent annual clinical assessments on depressive symptoms and cognitive function, and biennial [11C] Pittsburgh compound B‐PET and three‐dimensional MRI scans. Depression was defined based on the following: 1) depression diagnosed by a psychiatrist, 2) Geriatric Depression Scale score ≥ 11, or 3) the presence of any depressive symptom on Neuropsychiatric Inventory.ResultAmong the subjects, 73.4% (n = 212) were followed up for two years and twelve converted to mild cognitive impairment. Association between Aβ and depression was not observed at baseline. There was a significant Aβ positivity x Depression x Time interaction effect on hippocampal volume (F = 4.252, p = 0.042) and verbal memory (F = 7.488, p = 0.007) even after controlling for age, sex, educational level, APOE genotype, subjective memory complaint, and baseline white matter hyper intensity volume. Aβ positive individuals with depression showed faster decline of hippocampal atrophy and verbal memory decline than those in other subgroups for two years.ConclusionThe findings indicate that the presence of depression may accelerate hippocampal atrophy and episodic memory loss in older adults with preclinical AD.

Selective loss of episodic memory of odor percepts is associated with progression to amnestic MCI or Alzheimer’s disease in cognitively healthy seniors

AbstractBackgroundAccumulating evidence indicates that the pathological changes of AD begin 15 years prior to symptom onset. There is an unmet need for accessible, affordable, and accurate means to screen cognitively normal individuals for preclinical AD. We previously developed the Percepts of Odor Episodic Memory (POEM) test battery, which assesses identification, memory and discrimination of odor percepts. In a pilot study, we demonstrated that elderly individuals with odor memory scores that fell below the 50% confidence intervals of the memory scores predicted by their odor discrimination and odor identification scores; these individuals were deemed “at risk” for progression to mild cognitive impairment and AD based on an enrichment in biomarkers for AD.MethodWe tested our olfactory “at risk” status as a predictor of future decline by administering the POEM test battery to 61 older individuals who were cognitively normal (CN) or expressed subjective cognitive concerns (SCC) and were followed longitudinally in the Massachusetts Alzheimer’ s Disease Research Center. These individuals were added to our original sample of 140 participants who had undergone olfactory testing. A Cox Proportional Hazards model was used in a subset of this expanded cohort (n=127) who were followed over an average of 4.22 years to determine whether the olfactory “at risk” status predicted a risk of clinical progression to a diagnosis of amnestic MCI or Alzheimer’s disease.Result28% of the CN and SCC participants followed longitudinally were deemed “at risk” based on a selective odor memory loss. These “at risk” participants demonstrated a higher risk of progressing to amnestic MCI or AD (HR = 3.45, (95% CI:1.13‐10.72, p=0.0278) over time while controlling for age, education, and sex. The effect of Group (CN vs SCC) and its interaction with “at risk” status were not significant.ConclusionOur results indicate that probing olfactory function with a threshold based on personalized identification and discrimination abilities identifies cognitively healthy seniors who progress to amnestic MCI or AD at faster rate over time. Future work is focused on developing a remote version of this test for self‐administration that can be used to screen cognitively healthy individuals for research studies and clinical trials.

Novel Hybrid Acetylcholinesterase Inhibitors Induce Differentiation and Neuritogenesis in Neuronal Cells in vitro Through Activation of the AKT Pathway.

Alzheimer's disease (AD) is characterized by a progressive loss of episodic memory associated with amyloid-β peptide aggregation and the abnormal phosphorylation of the tau protein, leading to the loss of cholinergic function. Acetylcholinesterase (AChE) inhibitors are the main class of drugs used in AD therapy. The aim of the current study was to evaluate the potential of two tacrine-donepezil hybrid molecules (TA8Amino and TAHB3), which are AChE inhibitors, to induce neurodifferentiation and neuritogenesis in SH-SY5Y cells. The experiments were carried out to characterize neurodifferentiation, cellular changes related to responses to oxidative stress and pathways of cell survival in response to drug treatments. The results indicated that the compounds did not present cytotoxic effects in SH-SY5Y or HepG2 cells. TA8Amino and TAHB3 induced neurodifferentiation and neuritogenesis in SH-SY5Y cells. These cells showed increased levels of intracellular and mitochondrial reactive oxygen species; the induction of oxidative stress was also demonstrated by an increase in SOD1 expression in TA8Amino and TAHB3-treated cells. Cells treated with the compounds showed an increase in PTEN(Ser380/Thr382/383) and AKT(Ser473) expression, suggesting the involvement of the AKT pathway. Our results demonstrated that TA8Amino and TAHB3 present advantages as potential drugs for AD therapy and that they are capable of inducing neurodifferentiation and neuritogenesis.

Dehydrozingerone protects temozolomide-induced cognitive impairment in normal and C6 glioma rats besides enhancing its anticancer potential

Considering the cognitive impairment induced by temozolomide (TMZ) in glioblastoma survivors, the present study was aimed to evaluate the protective effect of dehydrozingerone (DHZ) against TMZ-induced cognitive impairment (chemobrain) and C6 cell line-induced glioma in male Wistar rats. In both chemobrain and glioma models, TMZ was administered at a dose of 18 mg/kg i.v every 5th day and DHZ at a dose of 100 mg/kg p.o. daily. Additionally, glioma was induced by intracerebral injection of 5 × 104 C6 rat glioma cells in the cortex in the glioma model. Upon disease induction and treatment with TMZ + DHZ, spatial memory was assessed by the Morris water maze (MWM) test and episodic memory by the novel object recognition test (NORT). The induction of glioma was confirmed by histology of the cortex. Hippocampus and frontal cortex were subjected to antioxidant evaluation. Significant loss of spatial and episodic memory was observed with TMZ treatment which was significantly restored by DHZ. DHZ showed significant improvement in oxidative stress markers reversed the histopathological features in the cortex. TMZ-induced elevation of the glutathione level was also reversed by DHZ, indicating the role of DHZ in the reversal of TMZ resistance. In the glioma model, the improvement in cognition by DHZ correlated with the decrease in tumor volume. Altogether, the study results reveal the role of TMZ in worsening the memory and DHZ in reversing it, besides, improving its anticancer potential.

Effect of ladostigil treatment of aging rats on gene expression in four brain areas associated with regulation of memory

Episodic and spatial memory decline in aging and are controlled by the hippocampus, perirhinal, frontal and parietal cortices and the connections between them. Ladostigil, a drug with antioxidant and anti-inflammatory activity, was shown to prevent the loss of episodic and spatial memory in aging rats. To better understand the molecular effects of aging and ladostigil on these brain regions we characterized the changes in gene expression using RNA-sequencing technology in rats aged 6 and 22 months. We found that the changes induced by aging and chronic ladostigil treatment were brain region specific. In the hippocampus, frontal and perirhinal cortex, ladostigil decreased the overexpression of genes regulating calcium homeostasis, ion channels and those adversely affecting synaptic function. In the parietal cortex, ladostigil increased the expression of several genes that provide neurotrophic support, while reducing that of pro-apoptotic genes and those encoding pro-inflammatory cytokines and their receptors. Ladostigil also decreased the expression of axonal growth inhibitors and those impairing mitochondrial function. Together, these actions could explain the protection by ladostigil against age-related memory decline.

Sleep-Wake Disturbances and Episodic Memory in Older Adults.

Sleep-wake disturbances have been associated with episodic memory loss, but past studies were limited by use of single measures of objective or perceived disturbances. Notably, cognitive reserve and depressive symptoms have been associated with sleep-wake disturbances and poorer episodic memory in older adults. The aims of this study were to determine the relationship between episodic memory and sleep-wake disturbances using objective and perceived measures in older adults and to examine cognitive reserve and depressive symptoms as moderators of this relationship. In this descriptive study, 62 healthy older adults (mean age: 69.9 years; 75.8% women) were recruited from the University of Michigan Clinical Research Program. Objective sleep-wake disturbances were measured by 7-day actigraphy and perceived sleep-wake disturbances by the Pittsburgh Sleep Quality Index and Epworth Sleepiness Scale. Episodic memory was measured by the Hopkins Verbal Learning Test-Revised. Analyses involved Pearson's correlation coefficients and hierarchical multiple regression. Results showed that more objectively measured sleep disruption was associated with poorer episodic memory and more perceived daytime sleepiness was associated with better episodic memory. Cognitive reserve and depressive symptoms were not moderators of this relationship. In this study, the relationship between sleep-wake disturbances and episodic memory differed by type of measure, objective or perceived. Future studies are needed using multiple measures of episodic memory to further understand the sleep-wake disturbances and episodic memory relationship in a larger diverse sample of healthy older adults.

Subjective feeling of re-experiencing past events using immersive virtual reality prevents a loss of episodic memory.

IntroductionPersonally meaningful past episodes, defined as episodic memories (EM), are subjectively re‐experienced from the natural perspective and location of one's own body, as described by bodily self‐consciousness (BSC). Neurobiological mechanisms of memory consolidation suggest how initially irrelevant episodes may be remembered, if related information makes them gain importance later in time, leading for instance, to a retroactive memory strengthening in humans.MethodsUsing an immersive virtual reality system, we were able to directly manipulate the presence or absence of one's body, which seems to prevent a loss of initially irrelevant, self‐unrelated past events.Results and ConclusionOur findings provide an evidence that personally meaningful memories of our past are not fixed, but may be strengthened by later events, and that body‐related integration is important for the successful recall of episodic memories.

Healthy ageing reduces the precision of episodic memory retrieval.

Episodic memory declines with older age, but it is unresolved whether this decline reflects reduced probability of successfully retrieving information from memory, or decreased precision of the retrieved information. Here, we used continuous measures of episodic memory retrieval in combination with computational mixture modeling of participants' retrieval errors to distinguish between these two potential accounts of age-related memory deficits. In three experiments, young and older participants encoded stimulus displays consisting of everyday objects varying along different perceptual features (e.g., location, color and orientation) in a circular space. At test, participants recreated the features of studied objects using a continuous response dial. Across all 3 experiments, we observed significant age-related declines in the precision of episodic memory retrieval, whereas significant age differences in retrieval success were limited to the most challenging task condition. Reductions in mnemonic precision were evident across different object features retained in long-term memory and persisted after controlling for age-related decreases in the fidelity of perception and working memory. The findings highlight impoverished precision of memory representations as one factor contributing to age-related episodic memory loss and suggest that the cognitive and neural changes associated with older age may differentially affect distinct aspects of episodic retrieval. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Proportion of cognitive loss attributable to terminal decline.

To estimate the proportion of late-life cognitive loss attributable to impending death. Older persons (n = 1,071) in a longitudinal cohort study without dementia at enrollment underwent annual cognitive assessments (mean 10.6 years, SD 4.6, range 4-24) prior to death. We estimated the onset of terminal acceleration in cognitive decline and rates of decline before and after this point in change point models that allowed calculation of the percent of cognitive loss attributable to terminal decline. Outcomes were composite measures of global and specific cognitive functions. We also estimated dementia and mild cognitive impairment (MCI) incidence before and during the terminal period. A mean of 3.7 years before death (95% credible interval [CI] -3.8 to -3.5), the rate of global cognitive decline accelerated to -0.313 unit per year (95% CI -0.337 to -0.290), a more than 7-fold increase indicative of terminal decline. The mean global cognitive score dropped 0.377 unit (SD 0.516) assuming no terminal decline and 1.192 units (SD 1.080) with terminal decline. As a result, 71% (95% bootstrapped CI 0.70, 0.73) of overall global cognitive loss was terminal. In subsequent analyses, terminal decline accounted for 70% of episodic memory loss, 65% of semantic memory loss, 57% of working memory loss, 52% of perceptual speed loss, and 53% of visuospatial loss. MCI incidence in the preterminal and terminal periods was similar, but dementia incidence was more than 6-fold higher in the terminal period than preterminal. Most late-life cognitive loss is driven by terminal decline.

ALCOHOL CONSUMPTION AND MEMORY: A LONGITUDINAL ANALYSIS OF RECIPROCAL IMPACTS ACROSS OLD AGE

Research on the association of alcohol consumption with cognitive aging revealed mixed evidence: Whereas a u-shaped relationship has been found in many studies, suggesting that low to moderate alcohol consumption predicts more favorable cognitive outcomes than abstinence, other findings suggest that alcohol is a more linearly related risk factor for cognitive decline. These inconsistencies may partly be due to methodological variation in the statistical modeling of intraindividual changes in both, alcohol consumption and cognition across old age. The present study analyzed longitudinal change in and the mutual effects between alcohol consumption habits and verbal episodic memory (word list recall), using vector autoregressive (VAR) mixed models with nonlinear cross-lagged effects. Data from the English Longitudinal Study of Ageing was examined, including N=13388 aged 50+ (M=67.6, SD=9.25; 54.7% female), assessed at up to eight occasions with two-year follow-up intervals (2002/3–2016/17). The self-reported one-year frequency of alcohol drinking days (ADD) served as indicator of alcohol consumption. Basically, ADD predicted follow-up memory performance in a reverse u-shaped fashion, indicating best memory performance after moderate ADD, compared with both ends of the ADD continuum (i.e., drinking never vs. every day). Considering moderators, most notably age did not interact with cross-lagged effects, suggesting that those observed across an older age-range were not more (or less) vulnerable to effects of alcohol consumption on memory performance. Thus, this study adds further support for non-detrimental, if not beneficial, effects of moderate alcohol consumption on cognitive aging – regarding in particular age-related loss of episodic memory.

Association between increased levels of amyloid-\u03b2 oligomers in plasma and episodic memory loss in Alzheimer\u2019s disease

ObjectiveThe objectives of this study were to investigate whether the plasma levels of oligomeric amyloid-β (OAβ) were affected in Alzheimer’s disease (AD) and to examine the associations (or possible correlations) between plasma OAβ levels and memory performance.MethodThirty subjects with AD and 28 cognitively normal controls were recruited in the study. The multimer detection system (MDS) was used to measure the levels of OAβ in the plasma. In addition to assessing the general cognitive function with the Mini-Mental State Examination (MMSE), Cognitive Abilities Screening Instrument (CASI), and Alzheimer’s Disease Assessment Scale–cognitive portion (ADAS-Cog), the common objects memory test (COMT) was used to examine the episodic memory performance. Pearson’s and partial correlation analyses were conducted to explore the associations between cognitive performance and OAβ levels in the plasma. A receiving operating curve (ROC) analysis was used to discriminate between the AD and control groups.ResultsThe plasma OAβ levels in the AD group were significantly higher than those in the control group [1.88 (0.38) ng/ml vs 1.20 (0.40) ng/ml, p < 0.001]. The elevated levels of plasma OAβ showed a strong correlation with cognitive performance in patients with AD, including an inverse correlation with scores on the MMSE (r = − 0.43, p = 0.02), CASI (r = − 0.56, p < 0.01), and the immediate recall (r = − 0.45, p = 0.01), 5-min delayed recall (r = − 0.56, p < 0.01), and 30-min delayed recall (r = − 0.71, p < 0.001) tests of the COMT, and a positive correlation with the ADAS-Cog scores (r = 0.59, p < 0.001). The EDTA plasma Aβ oligomer optical density (OD) value measured using the MDS could discriminate between the AD and control groups with an area under the curve (AUC) of 0.89. The optimal sensitivity and specificity were 82.1% and 90.0%, respectively.ConclusionThe elevated levels of OAβ in the plasma distinguished the AD and control groups and were associated with the severity of symptoms, especially memory performance, in patients with AD. Our results suggested that plasma OAβ could potentially be a simple and non-invasive blood-based biomarker for AD diagnosis. Furthermore, longitudinal studies are warranted to explore the application of plasma OAβ levels as a valid diagnostic biomarker in patients with AD.

Why Is Tetradentate Coordination Essential for Potential Copper Homeostasis Regulators in Alzheimer's Disease?

Research of effective drugs against Alzheimer's disease (AD) is currently one of the most challenging topics in medicinal chemistry. Despite the documented detrimental effect of the disruption of copper ion homeostasis in AD, this potential pharmacological target has been weakly explored. The design of chelators as drug candidates for copper regulation in AD brain should meet critical coordination chemistry requirements, in addition to requested biological parameters (membrane crossing, activity, …). Among the various possibilities offered by the diversity of metal ligands, we found that N4‐tetradentate 8‐aminoquinoline ligands able to generate stricly square planar Cu(II) complexes, are the most suitable for the transfer of copper from metal‐amyloids to metal‐carrier proteins, and are able to inhibit the catalytic reduction of dioxygen produced by copper‐loaded amyloids exposed to a biological reductant. In vivo, such tetradentate ligands are able to inhibit the loss of episodic memory in non‐transgenic amyloid‐impaired mice.