The Prevalence of Missing Incidents and Their Antecedents Among Older Adult MedicAlert Subscribers: Retrospective Descriptive Study.

BACKGROUND: With the population aging, the number of people living with dementia is expected to rise, which, in turn, is expected to lead to an increase in the prevalence of missing incidents due to critical wandering. However, the estimated prevalence of missing incidents due to dementia is inconclusive in some jurisdictions and overlooked in others. OBJECTIVE: The aims of the study were to examine (1) the demographic, psychopathological, and environmental antecedents to missing incidents due to critical wandering among older adult MedicAlert Foundation Canada (hereinafter MedicAlert) subscribers; and (2) the characteristics and outcomes of the missing incidents. METHODS: This study used a retrospective descriptive design. The sample included 434 older adult MedicAlert subscribers involved in 560 missing incidents between January 2015 and July 2021. RESULTS: The sample was overrepresented by White older adults (329/425, 77.4%). MedicAlert subscribers reported missing were mostly female older adults (230/431, 53.4%), living in urban areas with at least 1 family member (277/433, 63.8%). Most of the MedicAlert subscribers (345/434, 79.5%) self-reported living with dementia. MedicAlert subscribers went missing most frequently from their private homes in the community (96/143, 67.1%), traveling on foot (248/270, 91.9%) and public transport (12/270, 4.4%), during the afternoon (262/560, 46.8%) and evening (174/560, 31.1%). Most were located by first responders (232/486, 47.7%) or Good Samaritans (224/486, 46.1%). Of the 560 missing incidents, 126 (22.5%) were repeated missing incidents. The mean time between missing incidents was 11 (SD 10.8) months. Finally, the majority of MedicAlert subscribers were returned home safely (453/500, 90.6%); and reports of harm, injuries (46/500, 9.2%), and death (1/500, 0.2%) were very low. CONCLUSIONS: This study provides the prevalence of missing incidents from 1 database source. The low frequency of missing incidents may not represent populations that are not White. Despite the low number of missing incidents, the 0.2% (1/500) of cases resulting in injuries or death are devastating experiences that may be mitigated through prevention strategies.

Are We Talking About the Same Thing? Black/African Americans' Response to the BRFSS Cognitive Decline and Caregiver Modules.

The Behavioral Risk Factor Surveillance System (BRFSS) is a randomized national U.S. telephone survey administered by state health departments. This study aimed to identify how Black/African Americans understand BRFSS caregiver and cognitive decline surveys and terminology to inform health messaging that centers the Black/African American experience. In focus groups, BRFSS surveys were administered to Black/African Americans (n = 30) aged ≥ 45 in Oregon. Participants were asked how they interpreted BRFSS terms 'memory loss' and 'confusion,' how these terms related to Alzheimer's and dementia, and about caregiving and cognitive decline experiences. The culturally responsive Africana Worldview guided interpretation, which centers the Black/African American experience and individuals within interdependent relationships and community identity when explaining behaviors of people from the African diaspora. BRFSS survey responses differed from focus group responses to the same questions. Two participants reported providing care in the past two years on the survey; in discussions, 21 participants reported providing care in the past two years. Interpretations of BRFSS terminology varied greatly. Differences between age-related cognitive changes, dementia and Alzheimer's disease were unclear. Cognitive decline was largely understood in terms of identity loss and relationship changes with the affected individual, and how that individual's relationship changed within community. Caution is advised when using BRFSS data to frame messaging because key cognitive health terms are not universally understood. Messaging that apply the Africana Worldview centralizes relationships and community rather than impact on individual's day-to-day activities, may be more effective for Black/African Americans and for other groups with different cultural and life experiences.

Manasamitra Vatakam on Scopolamine-Induced Amnesia in Female Wistar Rats.

Background: Neurodegenerative diseases induce amnesia, and effective treatment is still elusive. Aims and Objectives: The present study highlights the ameliorating effects of Manasa Mitra Vatakam (MMV) using behavioral parameters on scopolamine-induced memory loss in female Wistar rats. Materials and Methods: MMV was compared with DPZ as a standard in the present study to determine the behavioral parameters through elevated plus maze (Hebb William maze/rectangular maze)and locomotor activity in scopolamine-induced memory loss in female Wistar rats. Results and Discussion: The results of the study illustrate the effectiveness of MMV in reversing memory dysfunction and memory-enhancing effects. Conclusion: The study paves the way for exploring research in CNS disorders and its potential application in drug-induced neurotoxicity.

Memory Support System in French: a Pilot Study.

Mild cognitive impairment (MCI) confers a higher risk of developing dementia. While largely preserved, instrumental activities of daily living (IADLs) may be affected to varying degrees by MCI. The Memory Support System (MSS) is a curriculum and calendar/note-taking system that has proven effective in sustaining independence in IADLs for individuals with MCI and in protecting mood among care partners. Until recently, the MSS has only been utilized among English- and Spanish-speaking samples. This study investigated the use of a translated and culturally adapted MSS in four French-speaking, community-dwelling participants with MCI and their support partners. Measures of treatment adherence, daily function, self-efficacy for memory, quality of life, mood, anxiety, and caregiver burden were assessed at baseline, treatment end, and eight-week follow-up. By treatment end and follow-up, participants with MCI showed improvement in adherence to the MSS calendar, IADLs, everyday abilities requiring memory and planning, self-efficacy, depression and anxiety symptoms, and quality of life. Care partners showed improvement in quality of life and depressive symptoms, while their caregiver burden and anxiety symptoms generally remained unchanged. Findings suggest that, with appropriate training, Francophones with MCI can and will use the MSS, and that MSS training may contribute to daily functioning and aspects of participant and care partner well-being.

Positive affect expression during a play interaction and psychological health among older adults living with cognitive impairment and their adult children.

OBJECTIVES: We examined the extent to which positive affect expression in play interactions between adult children and their parents living with cognitive impairment was associated with lower depressive symptoms and mental health difficulties for both dyad members. Gender differences in positive affect expression were also examined. METHOD: Dyads (N = 126) self-reported their depressive symptoms and mental health difficulties. Dyad members later engaged in a video-recorded play interaction together, and their positive affect expression was observationally coded by trained coders in terms of 'enjoyment', 'laughter', and 'positive affect towards partner'. RESULTS: Findings from mixed models using the Actor Partner Interdependence Model showed that one's partner's positive affect was associated with one's own lower depressive symptoms. There were no significant actor effects or effects of role (parent vs. child). Results also revealed that women expressed more positive affect and had greater mental health difficulties, but not depressive symptoms. We found that one's partner's positive affect expressions were more associated with women's mental health than men's mental health. CONCLUSION: Positive affect expression may be a useful indicator of psychological health in parent-child relationships in which the parent has cognitive impairment. Positive affect may be useful to target in supportive, dyadic, psychosocial interventions.

The WALLET Study: Financial Decision Making and Key Financial Behaviors Associated with Excess Spending.

OBJECTIVES: The Wealth Accumulation and Losses in Later life Early Cognitive Transitions (WALLET) study data was used to examine correlates with excess spending in older adults who do and do not have early memory loss. METHODS: The WALLET study collected detailed financial information from participants' primary checking account statements (n = 150). Information on participant sociodemographic, health, and disability status, memory functioning, financial decision-making, and financial literacy was also collected. Participants either had no memory problems or early memory loss. Bivariate and multiple regression analyses were conducted. RESULTS: The early memory loss group had significantly higher excess spending than those with no memory loss. Financial decision-making and higher-risk financial behaviors were also linked to higher excess spending. Early memory loss was no longer statistically significant after accounting for financial stressors and resources. CONCLUSIONS: The multidimensional nature of financial capacity assessment has long been known. The WALLET study data is unique, however, in that it demonstrates the links between excess spending with decision-making, early memory loss, and a set of specific financial behaviors. CLINICAL IMPLICATIONS: Real-world assessments of financial management and financial decision-making yield important information about how older adults are managing money and making key financial decisions. Checking account reviews can be used to determine excess spending.

Fish and Shellfish Consumption, Cognitive Health and Mortality from Alzheimer's Disease among US Adults Aged 60 and Older.

BACKGROUND: Relationships of fish-shellfish consumption, cognitive health and mortality from Alzheimer's disease (AD) among US adults aged 60 years and older have not been adequately studied. OBJECTIVES: To determine the relationship of fish-shellfish consumption, cognitive health and mortality from AD in US adults aged 60 years and older. DESIGN, SETTING AND PARTICIPANTS: The data of this cross-sectional study of US adults aged 60 years and older were from the National Nutrition and Health Examination Survey (NHANES) datasets. Frequency of fish-shellfish consumption, its association with subjective cognitive decline (SCD) and AD mortality of these participants between 1999 and 2018 and cognitive assessment scores between 2011 and 2014 were analyzed. MEASUREMENTS AND RESULTS: US adults aged 60 years and older consumed fish-shellfish 1.2 times/week and had a blood Hg of 1.63 ug/L on average between 1999 and 2018. Participants aged 60 years and older in the highest quartile of fish-shellfish consumption (~3 times/week) had significantly higher cognitive assessment scores than those in the lowest quartile (rare or no fish-shellfish consumption). Adults in the highest quartile of fish-shellfish consumption had a 30% lower risk (odds ratio 0.7, 95%CI 0.57-0.87) of SCD, and 44% lower risk (hazard ratio 0.56, 95%CI 0.35-0.9) of AD mortality than those in the lowest quartile. CONCLUSION: Increased fish-shellfish consumption was associated with improved scores of cognitive assessment and reduced risks of SCD and AD mortality.

Memory loss and aberrant neurogenesis in mice exposed to patient anti-N-methyl-d-aspartate receptor antibodies.

OBJECTIVE: Anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis results in chronic epilepsy and permanent cognitive impairment. One of the possible causes of cognitive impairment in anti-NMDAR could be aberrant neurogenesis, an established contributor to memory loss in idiopathic drug-resistant epilepsy. We developed a mouse model of anti-NMDAR encephalitis and showed that mice exposed to patient anti-NMDAR antibodies for 2 weeks developed seizures and memory loss. In the present study, we assessed the delayed effects of patient-derived antibodies on cognitive phenotype and examined the corresponding changes in hippocampal neurogenesis. METHODS: Monoclonal anti-NMDAR antibodies or control antibodies were continuously infused into the lateral ventricle of male C56BL/6J mice (8-12 weeks) via osmotic minipumps for 2 weeks. The motor and anxiety phenotypes were assessed using the open field paradigm, and hippocampal memory and learning were assessed using the object location, Y maze, and Barnes maze paradigms during weeks 1 and 3-4 of antibody washout. The numbers of newly matured granule neurons (Prox-1+) and immature progenitor cells (DCX+) as well as their spatial distribution within the hippocampus were assessed at these time points. Bromodeoxyuridine (BrdU, 50 mg/kg, i.p., daily) was injected on days 2-12 of the infusion, and proliferating cell immunoreactivity was compared in antibody-treated mice and control mice during week 4 of the washout. RESULTS: Mice infused with anti-NMDAR antibodies demonstrated spatial memory impairment during week 1 of antibody washout (p = 0.02, t-test; n = 9-11). Histological analysis of hippocampal sections from these mice revealed an increased ectopic displacement of Prox-1+ cells in the dentate hilus compared to the control-antibody-treated mice (p = 0.01; t-test). Mice exposed to anti-NMDAR antibodies also had an impairment of spatial memory and learning during weeks 3-4 of antibody washout (object location: p = 0.009; t-test; Y maze: p = 0.006, t-test; Barnes maze: p = 0.008, ANOVA; n = 8-10). These mice showed increased ratios of the low proliferating (bright) to fast proliferating (faint) BrdU+ cell counts and decreased number of DCX+ cells in the hippocampal dentate gyrus (p = 0.006 and p = 0.04, respectively; t-tests) suggesting ectopic migration and delayed cell proliferation. SIGNIFICANCE: These findings suggest that memory and learning impairments induced by patient anti-NMDAR antibodies are sustained upon removal of antibodies and are accompanied by aberrant hippocampal neurogenesis. Interventions directed at the manipulation of neuronal plasticity in patients with encephalitis and cognitive loss may be protective and therapeutically relevant.

How to lose your memory without losing your money: shifty epistemology and Dutch strategies.

An objection to shifty epistemologies such as subject-sensitive invariantism is that it predicts that agents are susceptible to guaranteed losses. Bob Beddor (Analysis, 81, 193-198, 2021) argues that these guaranteed losses are not a symptom of irrationality, on the grounds that forgetful agents are susceptible to guaranteed losses without being irrational. I agree that forgetful agents are susceptible to guaranteed losses without being irrational- but when we investigate why, the analogy with shifty epistemology breaks down. I argue that agents with shifty epistemologies are susceptible to guaranteed losses in a way which is a symptom of irrationality. Along the way I make a suggestion about what it takes for an agent to be coherent over time. I close by offering a taxonomy of shifty epistemologies.

A person-centered approach to financial capacity: early memory loss, financial management and decision-making.

OBJECTIVES: Previous research has noted that a person-centered approach to financial capacity assessment is feasible. This study of personal finance included a review of 12 months of checking account statements followed by research interviews to investigate income, spending, financial literacy, and financial decision-making. The objective of the study was to determine the convergent validity of excess spending to contextual aspects of financial decision-making, financial literacy, and early memory loss. METHOD: Participants were 114 adults over the age of 60 who came primarily from two research registries; the Healthier Black Elders registry and the Michigan Alzheimer's Disease Research Center registry. After sharing their checking statements participants completed two telephone interviews. Bivariate and multivariate analyses were used to compare those with no memory loss to the memory loss group, and to determine which measures were significantly related to excess spending. RESULTS: There was a significant difference in excess spending between those with early memory loss and those with no memory loss. There was a significant difference in financial decision-making risk scores between the groups, as well as on a memory measure and a financial literacy measure. In a hierarchical regression analysis financial decision-making was the only measure significantly related to excess spending. CONCLUSION: This study documented the convergent validity of person-centered measures of personal spending and financial decision-making with early memory loss. Early memory loss was related to both excess spending and contextual aspects of financial decision-making.

A Rare Case of Exercise-Induced Transient Global Amnesia as an Exclusive Presenting Symptom of Hippocampus Infarct.

Transient global amnesia (TGA) is a rare condition characterized by a temporary loss of the ability to form new memories. Retrograde episodic memory loss may also occur but to a lesser extent. Although TGA is generally benign, its sudden onset and similarity to more dangerous conditions like transient ischemic attack (TIA) or cerebral vascular accident (CVA) can be concerning. We present the case of a 70-year-old female who experienced confusion and general memory loss after a vigorous workout on her stationary exercise bike. After displaying considerable amnestic symptoms, she was admitted to the hospital for further medical attention and underwent a magnetic resonance imaging (MRI) that concluded a TGA diagnosis. This case report aims to investigate the prognosis associated with risk factors and refine the diagnostic criteria of TGA. We explore whether TGA caused by exercise, leading to unilateral or bilateral hippocampal lesions, is linked to cognitive decline. It is not yet clear if the development of TGA with unilateral infarct or bilateral hippocampal lesions results in different clinical presentations or varying prognoses. Further research is needed to determine the long-term risks of cognitive decline associated with resulting infarcts and clinical presentations.

Oxidative Stress, Endoplasmic Reticulum Stress and Apoptosis in the Pathology of Alzheimer's Disease.

Alzheimer's disease (AD) accounts for a major statistic among the class of neurodegenerative diseases. A number of mechanisms have been identified in its pathogenesis and progression which include the amyloid beta (Aß) aggregation, hyperphosphorylation of tau protein, oxidative stress, endoplasmic reticulum (ER) stress and apoptosis. These processes are interconnected and contribute significantly to the loss of neurons, brain mass and consequential memory loss and other cognitive difficulties. Oxidative stress in AD appears to be caused by excess of oxygen free radicals and extracellular Aß deposits that cause local inflammatory processes and activate microglia, another possible source of reactive oxygen species (ROS). ER Stress describes the accumulation of misfolded and unfolded proteins as a result of physiological and pathological stimuli including high protein demand, toxins, inflammatory cytokines, and mutant protein expression that disturbs ER homeostasis. When compared to age-matched controls, postmortem brain tissues from AD patients showed elevated levels of ER stress markers, such as PERK, eIF2α, IRE1α, the chaperone Grp78, and the downstream mediator of cell death CHOP. Apoptosis is in charge of eliminating unnecessary and undesired cells to maintain good health. However, it has been demonstrated that a malfunctioning apoptotic pathway is a major factor in the development of certain neurological and immunological problems and diseases in people, including neurodegenerative diseases. This article highlights and discussed some of the experimentally established mechanisms through which these processes lead to the development as well as the exacerbation of AD.

Stress-induced changes in cognitive function and intestinal barrier integrity can be ameliorated by venlafaxine and synbiotic supplementations.

Stress profoundly impacts various aspects of both physical and psychological well-being. Our previous study demonstrated that venlafaxine (Vlx) and synbiotic (Syn) treatment attenuated learned fear-like behavior and recognition memory impairment in immobilized-stressed rats. In this study, we further investigated the physical, behavior, and cellular mechanisms underlying the effects of Syn and/or Vlx treatment on brain and intestinal functions in stressed rats. Adult male Wistar rats, aged 8 weeks old were subjected to 14 days of immobilization stress showed a decrease in body weight gain and food intake as well as an increase in water consumption, urinary corticosterone levels, and adrenal gland weight. Supplementation of Syn and/or Vlx in stressed rats resulted in mitigation of weight loss, restoration of normal food and fluid intake, and normalization of corticosterone levels. Behavioral analysis showed that treatment with Syn and/or Vlx enhanced depressive-like behaviors and improved spatial learning-memory impairment in stressed rats. Hippocampal dentate gyrus showed stress-induced neuronal cell death, which was attenuated by Syn and/or Vlx treatment. Stress-induced ileum inflammation and increased intestinal permeability were both effectively reduced by the supplementation of Syn. In addition, Syn and Vlx partly contributed to affecting the expression of the glial cell-derived neurotrophic factor in the hippocampus and intestines of stressed rats, suggesting particularly protective effects on both the gut barrier and the brain. This study highlights the intricate interplay between stress physiological responses in the brain and gut. Syn intervention alleviate stress-induced neuronal cell death and modulate depression- and memory impairment-like behaviors, and improve stress-induced gut barrier dysfunction which were similar to those of Vlx. These findings enhance our understanding of stress-related health conditions and suggest the synbiotic intervention may be a promising approach to ameliorate deleterious effects of stress on the gut-brain axis.

The Short and Brave Life of Gaetano Perusini: A Tribute to His Role in Shaping Neuroscience.

Gaetano Perusini was an early enigma in neuroscience. In an age where myths and religion still held tightly to medical knowledge, Dr. Perusini was a trailblazer, inventor, and decorated forerunner. Born in Udine, worshiped in Italy, educated across Europe, published all over the western hemisphere, and taken away from us during a time of worldwide strife, his story continues to fascinate us today. This is a short chronicle of the major events in his life that also celebrates his widely acclaimed influence on understanding Alzheimer's disease.

A pilot study to assess blood-brain barrier permeability in long COVID.

The etiology of brain fog associated with long COVID is not clear. Based on some preliminary work, disruption of the blood-brain barrier has been hypothesized, but has not been tested in patients with long COVID. In this case-control pilot study, we evaluated blood-brain barrier permeability in patients with long COVID and subjective memory loss or brain fog. We used 99 m Technetium diethylenetriaminepentaacetic acid single-photon emission computed tomography (SPECT) to measure blood-brain barrier permeability and a telephone assessment (T-cog) to measure cognitive function. The blood-brain barrier permeability was quantified via SPECT standard uptake value (SUV). We assessed the blood-brain barrier permeability in 14 long COVID patients and 10 control participants without subjective cognitive impairment or brain fog. Participants in the two groups were similar in age. The long COVID group had more comorbidities compared to the control group. There was no difference in the SUVs in the long COVID (0.22 ± 0.12) vs the control (0.17 ± 0.04) group. There was no difference in the T-cog results in the two groups either. We found no evidence of a difference in blood-brain permeability in patients with long COVID when compared to controls without a known history of COVID-19 infection. Larger studies are needed to confirm these findings.

MyD88-mediated signaling is critical for the generation of seizure responses and cognitive impairment in a model of anti-N-methyl-D-aspartate receptor encephalitis.

OBJECTIVE: We previously demonstrated that interleukin-1 receptor-mediated immune activation contributes to seizure severity and memory loss in anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. In the present study, we assessed the role of the myeloid differentiation primary response gene 88 (MyD88), an adaptor protein in Toll-like receptor signaling, in the key phenotypic characteristics of anti-NMDAR encephalitis. METHODS: Monoclonal anti-NMDAR antibodies or control antibodies were infused into the lateral ventricle of MyD88 knockout mice (MyD88-/-) and control C56BL/6J mice (wild type [WT]) via osmotic minipumps for 2 weeks. Seizure responses were measured by electroencephalography. Upon completion of the infusion, the motor, anxiety, and memory functions of the mice were assessed. Astrocytic (glial fibrillary acidic protein [GFAP]) and microglial (ionized calcium-binding adaptor molecule 1 [Iba-1]) activation and transcriptional activation for the principal inflammatory mediators involved in seizures were determined using immunohistochemistry and quantitative real-time polymerase chain reaction, respectively. RESULTS: As shown before, 80% of WT mice infused with anti-NMDAR antibodies (n = 10) developed seizures (median = 11, interquartile range [IQR] = 3-25 in 2 weeks). In contrast, only three of 14 MyD88-/- mice (21.4%) had seizures (0, IQR = 0-.25, p = .01). The WT mice treated with antibodies also developed memory loss in the novel object recognition test, whereas such memory deficits were not apparent in MyD88-/- mice treated with anti-NMDAR antibodies (p = .03) or control antibodies (p = .04). Furthermore, in contrast to the WT mice exposed to anti-NMDAR antibodies, the MyD88-/- mice had a significantly lower induction of chemokine (C-C motif) ligand 2 (CCL2) in the hippocampus (p = .0001, Sidak tests). There were no significant changes in the expression of GFAP and Iba-1 in the MyD88-/- mice treated with anti-NMDAR or control antibodies. SIGNIFICANCE: These findings suggest that MyD88-mediated signaling contributes to the seizure and memory phenotype in anti-NMDAR encephalitis and that CCL2 activation may participate in the expression of these features. The removal of MyD88 inflammation may be protective and therapeutically relevant.

Alzheimer's Disease: The Past, Present, and Future of a Globally Progressive Disease.

Alzheimer's disease (AD) is a significant 21st-century public health challenge. This article delves into AD's neurodegenerative complexities, highlighting cognitive decline, memory impairment, and societal burdens. Mechanistically, protein misfolding, amyloid-beta (Aß) pathway abnormalities, and genetic/environmental factors are discussed. The pivotal amyloid hypothesis is dissected, focusing on Aß aggregation's role in synaptic dysfunction and neurodegeneration. The review showcases promising therapeutic strategies, including anti-amyloid antibodies and ß/γ-secretase inhibitors targeting Aß production. Notably, the FDA-approved Lecanemab signifies a breakthrough, slowing disease progression. Anti-Tau therapies' emergence is highlighted, addressing late-stage intervention. Tau aggregation blockers and anti-Tau antibodies offer potential against intracellular tau pathology. The review underscores collaborative efforts to uncover AD's secrets and pave the way for memory preservation.

Refining Cultural Adaptations of a Behavioral Intervention for Latino Caregivers of People Living With Dementia: Qualitative Interview Study in Washington State.

BACKGROUND:  In the United States, Latino caregivers of individuals with dementia face unique challenges and an elevated risk of adverse health outcomes. Despite the increasing prevalence of Alzheimer disease and related dementias among Latino adults, few evidence-based interventions are tailored to their cultural context. To address this gap, we examined the cultural adaptations required for the STAR caregivers (STAR-C) virtual intervention, an evidence-based intervention that educates family caregivers to manage behavioral and psychological symptoms of dementia. While STAR-C has shown effectiveness, neither the original in-person nor the virtual intervention considered the distinct experiences of Latino caregivers, who often bring culturally significant values into caregiving interactions. OBJECTIVE: This study's objective was to test and refine the preliminary cultural adaptations of the STAR-C web-based training modules for Latino caregivers of people living with dementia. METHODS: Through qualitative interviews with 15 Latino caregivers in Washington State, we identified key adaptations to enhance the cultural relevance of the web-based training modules. RESULTS: The interviews highlighted 4 main themes for adaptation: the delivery of the STAR-C web-based training modules, comprehensive dementia education, simplified problem-solving strategies, and prioritizing caregiver well-being. CONCLUSIONS: This study's findings informed the development of culturally adapted STAR-C web-based training modules that aim to provide tailored support to Latino caregivers. While further research is needed to assess the efficacy of these adaptations, our work contributes to bridging the gap in dementia caregiving for Latino families, potentially reducing health disparities and enhancing health care services for this population.

Locomotor Behavior and Memory Dysfunction Induced by 3-Nitropropionic Acid in Adult Zebrafish: Modulation of Dopaminergic Signaling.

Huntington's disease (HD) is a progressive neurodegenerative disease characterized by neuropsychiatric disturbance, cognitive impairment, and locomotor dysfunction. In the early stage (chorea) of HD, expression of dopamine D2 receptors (D2R) is reduced, whereas dopamine (DA) levels are increased. Contrary, in the late stage (bradykinesia), DA levels and the expression of D2R and dopamine D1 receptors (D1R) are reduced. 3-Nitropropionic acid (3-NPA) is a toxin that may replicate HD behavioral phenotypes and biochemical aspects. This study assessed the neurotransmitter levels, dopamine receptor gene expression, and the effect of acute exposure to quinpirole (D2R agonist) and eticlopride (D2R antagonist) in an HD model induced by 3-NPA in adult zebrafish. Quinpirole and eticlopride were acutely applied by i.p. injection in adult zebrafish after chronic treatment of 3-NPA (60 mg/kg). 3-NPA treatment caused a reduction in DA, glutamate, and serotonin levels. Quinpirole reversed the bradykinesia and memory loss induced by 3-NPA. Together, these data showed that 3-NPA acts on the dopaminergic system and causes biochemical alterations similar to late-stage HD. These data reinforce the hypothesis that DA levels are linked with locomotor and memory deficits. Thus, these findings may suggest that the use of DA agonists could be a pharmacological strategy to improve the bradykinesia and memory deficits in the late-stage HD.

Lack of causal association between epilepsy and dementia: A Mendelian randomization analysis.

OBJECTIVE: Epidemiological studies have reported an association between epilepsy and dementia. However, the causal relationship between epilepsy and the risk of dementia is not clear. We aimed to inspect the causal effect of epilepsy on memory loss and dementia. METHODS: We analyzed summary data of epilepsy, memory loss, and dementia from the genome-wide association study (GWAS) using the two-sample Mendelian randomization (MR) method. We used the estimated odds ratio of memory loss and dementia associated with each of the genetically defined traits to infer evidence for a causal relationship with the following exposures: all epilepsy, focal epilepsy (including focal epilepsy with hippocampal sclerosis, lesion-negative focal epilepsy, and focal epilepsy with other lesions), and genetic generalized epilepsy (including childhood absence epilepsy, generalized tonic-clonic seizures alone, Juvenile absence epilepsy, and Juvenile myoclonic epilepsy). RESULTS: According to the result of MR using the inverse variance weighted method (IVW), we found that genetically predicted epilepsy did not causally increase the risk of memory loss and dementia (p > 0.05). Results of the MR-Egger and weighted median method were consistent with the IVW method. CONCLUSIONS: No evidence has been found to support the notion that epilepsy can result in memory loss and dementia. The associations observed in epidemiological studies could be attributed, in part, to confounding or nongenetic determinants.