Tau and delirium superimposed on dementia: A case report.

We present a case involving a 60-year-old man with subacute delirium characterized by challenging attention shifts and obstinate behavior, contrasting with his usual mild-mannered personality. The patient developed pneumonia and a urinary tract infection following the onset of subacute delirium. Despite exhaustive investigations, the cause remained elusive until cerebrospinal fluid analysis revealed Tau positivity. Our overview suggests neurodegenerative diseases as the primary cause, rather than infectious or autoimmune factors. The case underscores a significant association between Tau and delirium superimposed on dementia, offering guidance to clinicians managing such patients.

Neuropsychiatric Symptoms Predict Faster Cognitive Decline in Dementia Collaborative Care Than Antipsychotic Use.

Background: To compare short-term cognitive outcomes among groups with and without neuropsychiatric symptoms (NPSs) or antipsychotic prescription and to determine which disease status or treatment modality is associated with relatively faster cognitive decline. Methods: We retrospectively analyzed a prospective cohort of patients diagnosed with dementia and mild cognitive impairment. All participants were evaluated using the Cognitive Abilities Screening Instrument (CASI) during their initial clinical assessments and at the annual follow-up. The dependent variable was annual delta CASI. Multivariate linear regression analysis was used to assess the degree of association between NPS, antipsychotic use, and cognitive decline after adjusting for confounding factors. Neuropsychiatric symptoms were examined individually to determine their predictive value for cognitive decline. Results: A total of 407 (N = 407) patients were included in the study. NPSs, rather than antipsychotic use, led to faster cognitive decline. A higher baseline NPI total score predicted a significantly faster decline in CASI scores (1-year delta CASI = -0.22, 95% CI = -0.38~ -0.05, p = 0.010). Specific items (delusions, agitation, depression, anxiety, euphoria, and apathy) in the NPS significantly increased cognitive decline. Conclusion: Certain neuropsychiatric symptoms, rather than antipsychotic use, lead to faster cognitive decline in a dementia collaborative care model. Checking for and providing appropriate interventions for NPS in people with dementia and their caregivers are highlighted.

Association of Parkinson's disease to Parkinson's plus syndromes, Lewy body dementia, and Alzheimer's dementia.

Background: Parkinson's disease (PD) is a condition that affects movement and is usually seen in those over the age of 50. It is caused by the death of dopaminergic neurons, particularly in the substantia nigra. PD has shifted from being perceived as an uncommon condition to a significant neurological illness, mostly due to the increasing number of elderly individuals and the impact of environmental factors. Parkinson's plus syndromes, such as progressive supranuclear palsy (PSP), multiple system atrophy (MSA), corticobasal degeneration (CBD), and vascular Parkinsonism (VaP), provide difficulties in distinguishing them clinically from PD since they have similar characteristics. Methodology: A thorough examination was performed utilizing the PubMed, Medline, Scopus, and Web of Science databases. The search utilized specific keywords like "Parkinson's disease," "Parkinson's plus syndrome," "Lewy body dementia," "Alzheimer's dementia," "progressive supranuclear palsy," and "multiple system atrophy." The selection criteria were aimed at English-language literature, with a particular focus on examining the connection between PD and associated disorders or dementias. Results and Discussion: Parkinson's plus syndromes, such as PSP, MSA, CBD, and VaP, exhibit unique clinical characteristics, imaging results, and diverse reactions to levodopa. This makes it difficult to distinguish them from PD. LBD is characterized by Lewy bodies containing α-synuclein, which leads to both motor and cognitive deficits. PD and Alzheimer's disease (AD) exhibit a complex interaction, including common pathogenic processes, genetic predispositions, and clinical characteristics of dementia. Conclusion: The interrelatedness of PD, Parkinson's plus syndromes, LBD, and AD highlights the significance of comprehending shared disease-causing processes. Aberrant protein clumping, impaired functioning of mitochondria, increased oxidative stress, and inflammation in the brain are common factors which can be addressed for specific treatments. More research is essential for understanding complicated connections and developing effective therapies for these sophisticated neurological illnesses.

Altered resting-state functional connectivity and dynamic network properties in cognitive impairment: an independent component and dominant-coactivation pattern analyses study.

Introduction: Cognitive impairment (CI) due to Alzheimer's disease (AD) encompasses a decline in cognitive abilities and can significantly impact an individual's quality of life. Early detection and intervention are crucial in managing CI, both in the preclinical and prodromal stages of AD prior to dementia. Methods: In this preliminary study, we investigated differences in resting-state functional connectivity and dynamic network properties between 23 individual with CI due to AD based on clinical assessment and 15 healthy controls (HC) using Independent Component Analysis (ICA) and Dominant-Coactivation Pattern (d-CAP) analysis. The cognitive status of the two groups was also compared, and correlations between cognitive scores and d-CAP switching probability were examined. Results: Results showed comparable numbers of d-CAPs in the Default Mode Network (DMN), Executive Control Network (ECN), and Frontoparietal Network (FPN) between HC and CI groups. However, the Visual Network (VN) exhibited fewer d-CAPs in the CI group, suggesting altered dynamic properties of this network for the CI group. Additionally, ICA revealed significant connectivity differences for all networks. Spatial maps and effect size analyses indicated increased coactivation and more synchronized activity within the DMN in HC compared to CI. Furthermore, reduced switching probabilities were observed for the CI group in DMN, VN, and FPN networks, indicating less dynamic and flexible functional interactions. Discussion: The findings highlight altered connectivity patterns within the DMN, VN, ECN, and FPN, suggesting the involvement of multiple functional networks in CI. Understanding these brain processes may contribute to developing targeted diagnostic and therapeutic strategies for CI due to AD.

Body Composition, Sarcopenic Obesity, and Cognitive Function in Older Adults: Findings From the National Health and Nutrition Examination Survey (NHANES) 1999-2002 and 2011-2014.

OBJECTIVE: Sarcopenic-obesity (SO) is characterized by the concomitant presence of low muscle mass and high adiposity. This study explores the association of body composition and SO phenotypes with cognitive function in older adults. METHODS: Cross-sectional data in older adults (≥60 years) from NHANES 1999-2002 and 2011-2014 were used. In the 1999-2002 cohort, phenotypes were derived from body mass index (BMI) and dual-X-ray-absorptiometry, and cognition was assessed the by Digit-Symbol-Substitution-Test (DSST). In the 2011-2014 cohort, phenotypes were derived from BMI, waist-circumference (WC), and hand-grip-strength (HGS). Cognition was assessed using four tests: DSST, Animal Fluency, the Consortium-to-Establish-a-Registry-for-Alzheimer's-Disease-Delayed-Recall, and Word Learning. Mediation analysis was conducted to evaluate the contribution of inflammation (C-reactive-protein, CRP) and insulin resistance (Homeostatic-Model-Assessment-for-Insulin-Resistance, HOMA-IR) to the association between body composition and cognitive outcomes. RESULTS: The SO phenotype had the lowest DSST mean scores (p < 0.05) and was associated with a significant risk of cognitive impairment [Odds Ratio (OR) = 1.9; 95%CI 1.0-3.7, p = 0.027] in the 1999-2002 cohort. A higher ratio of fat mass and fat free mass (FM/FFM) also showed a greater risk of cognitive impairment (OR = 2.0; 95%CI 1.3-3.1, p = 0.004). In the 2011-2014 cohort, the high WC-Low HGS group showed significantly lower scores on all four cognitive tests (p < 0.05) and a higher risk of cognitive impairment. CRP and HOMA-IR were significant partial mediators of the association between FM/FFM and DSST in the 1999-2002 cohort. CONCLUSIONS: The SO phenotype was associated with a higher risk of cognitive impairment in older adults. Insulin resistance and inflammation may represent key mechanisms linking SO to the development of cognitive impairment.

Catatonia in patients with dementia: A descriptive study of clinical profiles and treatment response.

BACKGROUND: Catatonia is a highly prevalent syndrome in patients presenting with major neurocognitive disorders (dementia). In this study, we aim to provide a comprehensive description of the clinical and therapeutic aspects of catatonia in patients with dementia. METHOD: This descriptive study, conducted between September 2015 and June 2022, collected data from 25 patients diagnosed with dementia, out of 143 patients treated for catatonia in our specialized psychiatry department. We collected sociodemographic, clinical and treatment data for each patient. RESULTS: Dementia patients constituted 17% of the catatonic cases. Predominantly female, the cohort had a mean age of 65. Diagnoses included Alzheimer's (4 patients, 17%) and Parkinson's (1 patient, 4%) diseases, Lewy body dementia (5 patients, 21%), vascular dementia (4 patients, 17%) and frontotemporal lobar degeneration (10 patients, 41%). The mean Bush-Francis Catatonia Rating Scale score upon admission was 20/69. Overall, complete remission of catatonia was achieved in 75% of patients (n=18), with only 13% (n=3) responding to lorazepam alone, while others required additional interventions such as electroconvulsive therapy (ECT) and/or amantadine. Vascular dementia was predominantly observed in cases resistant to treatment. CONCLUSION: The findings indicate a frequent co-occurrence of catatonia and dementia, highlighting treatability yet suggesting a potential for resistance to lorazepam, which varies by dementia diagnosis. Investigating the mechanisms underlying this resistance and the variability in treatment response is crucial for developing more precise therapeutic strategies.

Multitarget action of Benzothiazole-piperazine small hybrid molecule against Alzheimer's disease: In silico, In vitro, and In vivo investigation.

A novel small molecule based on benzothiazole-piperazine has been identified as an effective multi-target-directed ligand (MTDL) against Alzheimer's disease (AD). Employing a medicinal chemistry approach, combined with molecular docking, MD simulation, and binding free energy estimation, compound 1 emerged as a potent MTDL against AD. Notably, compound 1 demonstrated efficient binding to both AChE and Aß1-42, involving crucial molecular interactions within their active sites. It displayed a binding free energy (ΔGbind) -18.64± 0.16 and -16.10 ± 0.18 kcal/mol against AChE and Aß1-42, respectively. In-silico findings were substantiated through rigorous in vitro and in vivo studies. In vitro analysis confirmed compound 1 (IC50=0.42 µM) as an effective, mixed-type, and selective AChE inhibitor, binding at both the enzyme's catalytic and peripheral anionic sites. Furthermore, compound 1 demonstrated a remarkable ability to reduce the aggregation propensity of Aß, as evidenced by Confocal laser scanning microscopy and TEM studies. Remarkably, in vivo studies exhibited the promising therapeutic potential of compound 1. In a scopolamine-induced memory deficit mouse model of AD, compound 1 showed significantly improved spatial memory and cognition. These findings collectively underscore the potential of compound 1 as a promising therapeutic candidate for the treatment of AD.

Socially Assistive Robots for patients with Alzheimer's Disease: A scoping review.

BACKGROUND: The most common form of dementia, Alzheimer's Disease (AD), is challenging for both those affected as well as for their care providers, and caregivers. Socially assistive robots (SARs) offer promising supportive care to assist in the complex management associated with AD. OBJECTIVES: To conduct a scoping review of published articles that proposed, discussed, developed or tested SAR for interacting with AD patients. METHODS: We performed a scoping review informed by the methodological framework of Arksey and O'Malley and adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) checklist for reporting the results. At the identification stage, an information specialist performed a comprehensive search of 8 electronic databases from the date of inception until January 2022 in eight bibliographic databases. The inclusion criteria were all populations who recive or provide care for AD, all interventions using SAR for AD and our outcomes of inteerst were any outcome related to AD patients or care providers or caregivers. All study types published in the English language were included. RESULTS: After deduplication, 1251 articles were screened. Titles and abstracts screening resulted to 252 articles. Full-text review retained 125 included articles, with 72 focusing on daily life support, 46 on cognitive therapy, and 7 on cognitive assessment. CONCLUSION: We conducted a comprehensive scoping review emphasizing on the interaction of SAR with AD patients, with a specific focus on daily life support, cognitive assessment, and cognitive therapy. We discussed our findings' pertinence relative to specific populations, interventions, and outcomes of human-SAR interaction on users and identified current knowledge gaps in SARs for AD patients.

Impaired Kidney Function, Cerebral Small Vessel Disease and Cognitive Disorders: The Framingham Heart Study.

BACKGROUND AND HYPOTHESIS: It remains unclear if the relation of chronic kidney disease (CKD) with cognitive dysfunction is independent of blood pressure (BP). We evaluated kidney function in relation to premorbid BP measurements, cerebral small vessel disease (CSVD) and incident mild cognitive impairment (MCI) and dementia in Framingham Offspring Cohort participants. METHODS: We included Framingham Offspring participants free of dementia, attending an examination during midlife (exam cycle 6, baseline) for ascertainment of kidney function status, with brain MRI late in life (exam cycles 7-9), cognitive outcome data and available interim hypertension and blood pressure assessments. We related CKD (estimated glomerular filtration rate < 60 ml/min/1.73m2) and albuminuria (urine albumin-to-creatinine ratio ≥ 30 mg/g) to CSVD markers and cognitive outcomes using multivariable regression analyses. RESULTS: Among 2604 participants (mean age 67.4 ± 9.2, 64% women, 7% had CKD and 9% albuminuria), albuminuria was independently associated with covert infarcts (adjusted OR, 1.55 [1.00-2.38]; P = 0.049) and incident MCI and dementia (adjusted HR, 1.68 [1.18-2.41]; P = 0.005 and 1.71, [1.11-2.64]; P = 0.015, respectively). CKD was not associated with CSVD markers but was associated with higher risk of incident dementia (HR, 1.53 [1.02-2.29]; P = 0.041), While albuminuria was predictive of the Alzheimer's disease subtype (Adjusted HR = 1.68, [1.03-2.74]; P = 0.04), CKD was predictive of vascular dementia (Adjusted HR, 2.78, [1.16-6.68]; P = 0.023). CONCLUSIONS: Kidney disease was associated with CSVD and cognitive disorders in asymptomatic community dwelling participants. The relation was independent of premorbid BP, suggesting that the link between kidney and brain disease may involve additional mechanisms beyond blood pressure related injury.

Predicting cognitive function and dementia risk in patients with hypertension.

In spite of the fact that hypertension stand out as the main vascular risk factor for developing dementia, it is essential to acknowledge the presence of other risk factors, both vascular and non-vascular that contribute to increase this risk. This study stratified the dementia risk using CAIDE (Cardiovascular Risk Factors, Aging, and Incidence of Dementia) dementia risk score in a sample of 1279 hypertensive patients from the Heart-Brain Study in Argentina and to observed the association between the risk factors include in the CAIDE score and the current cognitive status. The average age of the sample was 60.2 ± 13.5 years (71% female) and the average years of education was 9.9 ± 5.1 years. To assess the current cognitive status, we used the Mini-mental test (MMSE), the clock drawing test (CDT) and Mini-Boston test. According to CAIDE score ( ≥9 points) the risk of dementia was 40.4% in the total sample and 28.1% in the middle-life hypertensive patients (between 47 to 53 years). An inverse association was observed between CAIDE score and the results of current cognitive tests (MMSE = R2 0.9128, p < 0.0001; CDT = R2 0.9215, p < 0.0001 y Mini-Boston= R2 0.829, p < 0.0001). The CAIDE score can predict the risk of dementia in hypertensive patients and its result was associated with the current cognitive status (result of cognitive tests).

A Hypermutable Region in the DISP2 Gene Links to Natural Selection and Late-Onset Neurocognitive Disorders in Humans.

(CCG) short tandem repeats (STRs) are predominantly enriched in genic regions, mutation hotspots for C to T truncating substitutions, and involved in various neurological and neurodevelopmental disorders. However, intact blocks of this class of STRs are widely overlooked with respect to their link with natural selection. The human neuron-specific gene, DISP2 (dispatched RND transporter family member 2), contains a (CCG) repeat in its 5' untranslated region. Here, we sequenced this STR in a sample of 448 Iranian individuals, consisting of late-onset neurocognitive disorder (NCD) (N = 203) and controls (N = 245). We found that the region spanning the (CCG) repeat was highly mutated, resulting in several flanking (CCG) residues. However, an 8-repeat of the (CCG) repeat was predominantly abundant (frequency = 0.92) across the two groups. While the overall distribution of genotypes was not different between the two groups (p > 0.05), we detected four genotypes in the NCD group only (2% of the NCD genotypes, Mid-p = 0.02), consisting of extreme short alleles, 5- and 6-repeats, that were not detected in the control group. The patients harboring those genotypes received the diagnoses of probable Alzheimer's disease and vascular dementia. We also found six genotypes in the control group only (2.5% of the control genotypes, Mid-p = 0.01) that consisted of the 8-repeat and extreme long alleles, 9- and 10-repeats, of which the 10-repeat was not detected in the NCD group. The (CCG) repeat specifically expanded in primates. In conclusion, we report an indication of natural selection at a novel hypermutable region in the human genome and divergent alleles and genotypes in late-onset NhCDs and controls. These findings reinforce the hypothesis that a collection of rare alleles and genotypes in a number of genes may unambiguously contribute to the cognition impairment component of late-onset NCDs.

Evaluating the validity and reliability of the Korean version of Scales for Outcomes in Parkinson's Disease-Cognition.

Objective: The Scales for Outcomes in Parkinson's Disease-Cognition (SCOPA-Cog) was developed to screen for cognition in PD. In this study, we aimed to evaluate the validity and reliability of the Korean version of the SCOPA-cog. Methods: We recruited 129 PD patients from 31 clinics with movement disorders in South Korea. The original version of the SCOPA-cognition was translated into Korean using the translation-retranslation method. The test-rest method with an intraclass correlation coefficient (ICC) and Cronbach's alpha coefficient were used to assess reliability. The Spearman's Rank correlation analysis with Montreal Cognitive Assessment-Korean version (MOCA-K) and Korean Mini-Mental State Examination (K-MMSE) were used to assess concurrent validity. Results: The Cronbach's alpha coefficient was 0.797, and the ICC was 0.887. Spearman's rank correlation analysis showed a significant correlation with the K-MMSE and MOCA-K scores (r = 0.546 and r = 0.683, respectively). Conclusions: Our results demonstrate that K-SCOPA-Cog exhibits good reliability and validity.

Social cognition differentiates phenocopy syndrome of behavioural variant frontotemporal dementia from behavioural variant frontotemporal dementia.

BACKGROUND: Patients displaying clinical features of behavioural variant of frontotemporal dementia (bvFTD) but lacking both neuroimaging abnormalities and clinical progression are considered to represent the phenocopy syndrome of bvFTD (phFTD). Extensive clinical overlap between early phase bvFTD and phFTD hampers diagnostic distinction. We aimed to assess the diagnostic value of clinician-rated, self-reported and caregiver-reported symptoms for clinical distinction between phFTD and bvFTD. METHODS: There were 33 phFTD and 95 probable bvFTD patients included in the study (total N = 128). Clinician-rated, self-reported tests and caregiver-reported symptoms were compared between phFTD and bvFTD on social cognition, behaviour, mood and activities of daily living (ADL). Scores were compared between groups, followed by multiple logistic regression analysis, adjusted for age and sex. Receiver operating characteristic curves were plotted to assess diagnostic value. RESULTS: Using clinician-rated and self-reported tests, phFTD patients performed better on facial emotion recognition and reported more depressive symptoms. Caregiver-reported behavioural symptoms indicated higher behavioural and ADL impairment in phFTD compared to bvFTD. Facial emotion recognition provided highest diagnostic accuracy for distinction of phFTD from bvFTD (area under the curve (AUC) 0.813 95% CI 0.735-0.892, P < 0.001, sensitivity 81%, specificity 74%) followed by depressive symptoms (AUC 0.769 95% 0.674-0.864, P < 0.001 sensitivity 81%, specificity of 63%). CONCLUSION: Social cognition tests are most suitable for distinction of phFTD from bvFTD. Caregiver-reported questionnaires and phFTD diagnosis seemed inversely correlated, showing more symptoms in phFTD. Further research is needed on phFTD aetiology and in caregivers taking into account disease burden to assess what explains this discrepancy between clinician-rated and caregiver-based tools.

Effect of digital technology interventions for cognitive function improvement in mild cognitive impairment and dementia: A systematic review and meta-analysis.

The development and commercialization of digital therapeutics are increasing. The aim of this study was to determine the effects of digital technology interventions on cognitive function, thereby providing evidence for the development and practical application of interventions to manage cognitive function in patients with mild cognitive impairment and dementia. We conducted a systematic review and meta-analysis of randomized controlled trials according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines. Randomized controlled trials on digital technology interventions published until April 2023 were searched in PubMed, Embase, Cochrane Library, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases without a period limit. Articles that identified the effects of digital technology interventions on cognitive function improvement in dementia and mild cognitive impairment were integrated and analyzed. RevMan software 5.4 was used for quality assessment and meta-analysis. Twelve out of 708 studies were included in the review and meta-analysis. Digital technology interventions had significant effects on global cognitive function (standardized mean difference [SMD] = 0.31; 95% confidence interval [CI] = 0.04-0.57; p = 0.02; I² = 60%). In addition, these interventions had significant effects on neuropsychological characteristics, including attention (SMD = 1.17; 95% CI = 0.36-1.97; p = 0.004; I² = 84%), visuospatial perception (SMD = 0.68; 95% CI = 0.19-1.17; p = 0.006; I² = 57%), and memory (SMD = 0.45; 95% CI = 0.19-0.71; p = 0.0007; I² = 22%). The results suggest that digital technology interventions help improve cognitive function in patients with dementia and mild cognitive impairment.

Childhood book availability helps to preserve cognitive function in older adults with low education: Results from the NEIGE study.

OBJECTIVES: It is well-known that low educational attainment is associated with cognitive function decline in older age. Childhood book availability may help to preserve cognitive function in older adults with low education. The study objective was to examine the association between childhood book availability and cognitive function among older adults with low educational attainment, and to investigate the mediating effect of the volume of reading-related brain regions (e.g., superior temporal cortex). METHODS: A cross-sectional study of community-dwelling older Japanese adults aged 65-84 years was conducted (n=474). Cognitive function was assessed using the Mini-Mental State Examination (MMSE). Childhood book availability was assessed using a retrospective questionnaire. Brain region volume was measured using magnetic resonance imaging. Multivariate regression modeling and structural equation modeling were used for analysis. RESULTS: Both high educational attainment and childhood book availability were independently associated with high MMSE score. Stratification of educational level showed that childhood book availability was positively associated with MMSE score among participants with low educational attainment (coefficient=1.48, 95% confidence interval (CI): 0.31 to 2.66), but not among those with moderate or high educational attainment (coefficient=-0.01, 95% CI: -1.44 to 1.42 and -1.21, 95% CI: -3.85 to 1.42, respectively). Among participants with low educational attainment, left superior temporal cortex volume mediated the association between childhood book availability and MMSE score. DISCUSSION: The availability of books in childhood helps to preserve cognitive function in older adults with low education via left superior temporal cortex volume. Further research is needed to replicate these findings.

Do clinical guidelines support person-centred care for women affected by dementia: A content analysis.

BACKGROUND: Dementia disproportionately affects women including persons living with dementia and caregivers. Person-centered care, rather than disease-focused, is recommended to improve care for affected persons including caregivers. General practitioners play a central role in dementia care but find it challenging due to inadequate training. The study aimed to assess if and how dementia guidelines provide clinicians with guidance on person-centred care for women affected by dementia. METHODS: We searched for publicly available English-language guidelines on the overall management of dementia in MEDLINE, EMBASE and the Guidelines International Network repository. We employed deductive and summative content analysis, and categorized person-centered care guideline content based on established frameworks, and conveyed our results using summary statistics, text, and tables. RESULTS: We reviewed 15 guidelines published from 2006 to 2020 in eight countries. Few (4, 23%) involved persons living with dementia or caregivers in guideline development. Regarding general person-centred care, guidelines mostly addressed the domains of exchange information (93%), share decisions (93%), enable self-management (93%) and address emotions (87%), while few offered content on manage uncertainty (33%) or foster a healing relationship (13%). Regarding dementia-specific person-centred care, most guidelines addressed intersectionality (tailoring care for diverse characteristics) (80%), but few included content on the domains of quality of life (67%), dignity (53%) or sex/gender issues (20%). Even when mentioned, the guidance was typically brief. We identified 32 general and 18 dementia-specific strategies to achieve person-centered care by compiling information from these guidelines. CONCLUSIONS: This study identified inconsistent and insufficient guideline content on person-centred care for women with dementia. Compiled strategies for achieving person-centred care could be used by developers to enhance existing and future dementia guidelines; and inform the development of policies or programs, education, tools for clinicians, and quality improvement measures for evaluating dementia care. Future research is crucial for promoting person-centred dementia care for women living with dementia.

Gender differences in the associations of psychosocial trauma and acute medical stressors with immune system activation and dementia risk.

Objective: The purpose of this article is to provide a narrative review synthesizing the literature on differences between women and men in relationships among certain stressors associated with immune system activation and their relationship to cognitive dysfunction and dementia. Method: We review the cycle of stress leading to neuroinflammation via cortisol and neurochemical alterations, cell-mediated immune system activation, and pro-inflammatory cytokines, and how this is implicated in the development of dementia. We follow this by discussing sex differences in stress physiology and immune function. We then review the work on early life adversity (ELA) and adverse childhood experiences (ACEs), post-traumatic stress disorder, acute medical stressors, and their associations with cognitive dysfunction and dementia. Throughout, we emphasize women's presentations and issues unique to women (e.g. trauma disorder prevalence). Conclusions: There is a need for more mechanistic and longitudinal studies that consider trauma accumulation, both physical and emotional, as well as a greater focus on traumas more likely to occur in women (e.g. sexual abuse), and their relationship to early cognitive decline and dementia.

Effects of a Person's Lactation History on Later-Life Development of Alzheimer's Disease: An Integrative Review.

Objective: The purpose of this integrative review is to assess the existing evidence regarding the effects of a person's lactation history on later-life development of Alzheimer's disease. Methods: The authors searched the electronic databases PubMed, Cumulative Index to Nursing and Allied Health Literature, Scopus, and Excerpta Medica dataBASE, and performed backward reference searches using search terms such as, "Alzheimer's disease, dementia," and "breastfeeding, lactation." Authors selected relevant records through the application of inclusion and exclusion criteria and reading the titles, abstracts, or records in full. Results: In total, 400 articles were identified, and 10 articles meeting inclusion criteria were analyzed. Authors extracted data following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and scored levels of evidence according to Melnyk and Fineout-Overholt. Data were organized according to themes of breastfeeding duration, ever having breastfed, and indirect effects of breastfeeding. Conclusions: Breastfeeding may have neuroprotective effects for the lactating person and reduce the risk of later-life development of Alzheimer's disease. However, future research is necessary to determine the generalizability of this association.

Clinicopathological study of dementia with grains presenting with parkinsonism compared with a typical case.

Argyrophilic grain disease (AGD) is one of the major pathological backgrounds of senile dementia. Dementia with grains refers to cases of dementia for which AGD is the sole background pathology responsible for dementia. Recent studies have suggested an association between dementia with grains and parkinsonism. In this study, we aimed to present two autopsy cases of dementia with grains. Case 1 was an 85-year-old man who exhibited amnestic dementia and parkinsonism, including postural instability, upward gaze palsy, and neck and trunk rigidity. The patient was clinically diagnosed with progressive supranuclear palsy and Alzheimer's disease. Case 2 was a 90-year-old man with pure amnestic dementia, clinically diagnosed as Alzheimer's disease. Recently, we used cryo-electron microscopy to confirm that the tau accumulated in both cases had the same three-dimensional structure. In this study, we compared the detailed clinical picture and neuropathological findings using classical staining and immunostaining methods. Both cases exhibited argyrophilic grains and tau-immunoreactive structures in the brainstem and basal ganglia, especially in the nigrostriatal and limbic systems. However, Case 1 had more tau immunoreactive structures. Considering the absence of other disease-specific structures such as tufted astrocytes, astrocytic plaques and globular glial inclusions, lack of conspicuous cerebrovascular disease, and no history of medications that could cause parkinsonism, our findings suggest an association between AGD in the nigrostriatal system and parkinsonism.