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Alzheimer's disease is the most common type of dementia that currently affects over 6.5 million people in the U.S. Currently there is no cure and the existing drug therapies attempt to delay the mental decline and improve cognitive abilities. Two of the most commonly prescribed such drugs are Donepezil and Memantine. We formally tested and confirmed the presence of a beneficial drug-drug interaction of Donepezil and Memantine using a causal inference analysis. We applied doubly robust estimators to one of the largest and high-quality medical databases to estimate the effect of two commonly prescribed Alzheimer's disease (AD) medications, Donepezil and Memantine, on the average number of hospital or emergency department visits per year among patients diagnosed with AD. Our results show that, compared to the absence of medication scenario, the Memantine monotherapy, and the Donepezil monotherapy, the combined use of Donepezil and Memantine treatment significantly reduces the average number of hospital or emergency department visits per year by 0.078 (13.8%), 0.144 (25.5%), and 0.132 days (23.4%), respectively. The assessed decline in the average number of hospital or emergency department visits per year is consequently associated with a substantial reduction in medical costs. As of 2022, according to the Alzheimer's Disease Association, there were over 6.5 million individuals aged 65 and older living with AD in the US alone. If patients who are currently on no drug treatment or using either Donepezil or Memantine alone were switched to the combined used of Donepezil and Memantine therapy, the average number of hospital or emergency department visits could decrease by over 613 thousand visits per year. This, in turn, would lead to a remarkable reduction in medical expenses associated with hospitalization of AD patients in the US, totaling over 940 million dollars per year. [ABSTRACT FROM AUTHOR]

INTRODUCTION: The association between neuropathological changes and dementia among centenarians and nonagenarians remains unclear. METHODS: We examined brain tissue from 100 centenarians and 297 nonagenarians from The 90+ Study, a community‐based longitudinal study of aging. We determined the prevalence of 10 neuropathological changes and compared their associations with dementia and cognitive performance between centenarians and nonagenarians. RESULTS: A total of 59% of centenarians and 47% of nonagenarians had at least four neuropathological changes. In centenarians, neuropathological changes were associated with higher odds of dementia and, compared to nonagenarians, the odds were not attenuated. For each additional neuropathological change, the Mini‐Mental State Examination score was lower by 2 points for both groups. DISCUSSION: Neuropathological changes continue to be strongly related to dementia in centenarians, highlighting the importance of slowing or preventing the development of multiple neuropathological changes in the aging brain to maintain cognitive health. Highlights: Individual and multiple neuropathological changes are frequent in centenarians.These neuropathological changes are strongly associated with dementia.There is no attenuation of this association with age. [ABSTRACT FROM AUTHOR]

Background: Aflatoxin B1 (AFB1) is one of the most important mycotoxins that contaminate food worldwide. Long- term consumption of foods contaminated with AFB1 endangers human health. Detoxification of AFB1 from food improves community health. A Specific approach to aflatoxin reduction is the use of probiotics. Kefir drink is a strong probiotic. The purpose of this study was to investigate the protective effect of kefir drink on AFB1-induced hepatic injury in adult male rats Methods: In this experimental study, 24 adult rats weighing between 150 and 200 g were used. The rats were randomly divided into 4 groups: 1) control, 2) AFB1 (50 μg/kg body weight), 3) kefir drink (10 mL/kg body weight), and 4) AFB1 + kefir drink. Aflatoxin and kefir drink received through oral gavage. At the end of the experiment (8 weeks), blood and liver samples were collected for different assays. Liver function tests and histopathological examinations were performed. Data were analyzed using 1-way analysis of variance (ANOVA) and at a significance level of <0.05. Results: Aflatoxin B1 significantly increased serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin (T.Bili), as well as decreased total protein (T.P) content, compared to the control group (P < 0.05). Aflatoxin B1 induced histological changes in the liver. The results obtained from the groups treated with kefir drink with and without AFB1 were not significantly different from the control group. Histopathological changes were not found in groups treated with kefir drink with and without AFB1. Conclusion: The consumption of kefir drink reduced AFB1-induced disruptions in rats’ livers. [ABSTRACT FROM AUTHOR]

Despite decades of research on the relation between thyroid diseases and cognition, the nature of this relationship remains elusive. An increasing prevalence of cognitive impairment and thyroid dysfunction has been consistently observed with ageing. Also, there appears to be an association between thyroid disorders and cognitive decline. Given the increasing global burden of dementia, elucidating the relationship between thyroid disorders as a potentially modifiable risk factor of cognitive impairment was the main goal of this review. We summarise the current literature examining the relationship between thyroid hormonal dysregulation and cognition or behaviour. We present the available imaging and pathological findings related to structural and functional brain changes related to thyroid hormonal dysregulation. We also propose potential mechanisms of interaction between thyroid hormones, autoantibodies and cognition/behaviour. Effects of gender, ethnicity and environmental factors are also briefly discussed. This review highlights the need for long‐term prospective studies to capture the course of brain functional changes associated with the incidence and progression of thyroid dysregulations along with the confounding effects of non‐modifiable risk factors such as gender and ethnicity. Moreover, double‐blind controlled clinical trials are necessary to devise appropriate treatment plans to prevent cognitive consequences of over or undertreatment of thyroid disorders. [ABSTRACT FROM AUTHOR]

Purpose of review: The fastest-growing group of elderly individuals is the “oldest-old,” usually defined as those age 85 years and above. These individuals account for much of the rapid increase in cases of dementing illness throughout the world but remain underrepresented in the body of literature on this topic. The aim of this review is first to outline the unique contributing factors and complications that must be considered by clinicians in evaluating an oldest-old individual with cognitive complaints. Secondly, the evidence for management of these cognitive concerns is reviewed. Recent findings: In addition to well-established associations between impaired cognition and physical disability, falls, and frailty, there is now evidence that exercise performed decades earlier confers a cognitive benefit in the oldest-old. Moreover, though aggressive blood pressure control is critical earlier in life for prevention of strokes, renal disease, and other comorbidities, hypertension started after age 80 is in fact associated with a decreased risk of clinical dementia, carrying significant implications for the medical management of oldest-old individuals. The oldest-old are more likely to reside in care facilities, where social isolation might be exacerbated by a consistently lower rate of internet-connected device use. The COVID-19 pandemic has not only highlighted the increased mortality rate among the oldest-old but has also brought the increased social isolation in this group to the forte. Summary: Differing from the “younger-old” in a number of respects, the oldest-old is a unique population not just in their vulnerability to cognitive disorders but also in the diagnostic challenges they can pose. The oldest-old are more likely to be afflicted by sensory deficits, physical disability, poor nutrition, frailty, and depression, which must be accounted for in the assessment of cognitive complaints as they may confound or complicate the presentation. Social isolation and institutionalization are also associated with impaired cognition, perhaps as sequelae, precipitants, or both. Ante-mortem diagnostic tools remain particularly limited among the oldest-old, especially given the likelihood of these individuals to have multiple co-occurring types of neuropathology, and the presence of neuropathology in those who remain cognitively intact. In addition to the symptomatic treatments indicated for patients of all ages with dementia, management of cognitive impairment in the oldest-old may be further optimized by use of assistive devices, augmentation of dietary protein, and liberalization of medication regimens for risk factors such as hypertension. [ABSTRACT FROM AUTHOR]

Purpose: We sought to examine interrater reliability in clinical assessment of apraxia of speech (AOS) in individuals with primary progressive aphasia and to identify speech characteristics predictive of AOS diagnosis. Method: Fifty-two individuals with primary progressive aphasia were recorded performing a variety of speech tasks. These recordings were viewed by 2 experienced speechlanguage pathologists, who independently rated them on the presence and severity of AOS as well as 14 associated speech characteristics. We calculated interrater reliability (percent agreement and Cohen’s kappa) for these ratings. For each rater, we used stepwise regression to identify speech characteristics significantly predictive of AOS diagnosis. We used the overlap between raters to create a more parsimonious model, which we evaluated with multiple linear regression. Results: Results yielded high agreement on the presence (90%) and severity of AOS (weighted Cohen’s κ = .834) but lower agreement for specific speech characteristics (weighted Cohen’s κ ranging from .036 to .582). Stepwise regression identified 2 speech characteristics predictive of AOS diagnosis for both raters (articulatory groping and increased errors with increased length/complexity). These alone accounted for ≥ 50% of the variance of AOS severity in the constrained model. Conclusions: Our study adds to a growing body of research that highlights the difficulty in objective clinical characterization of AOS and perceptual characterization of speech features. It further supports the need for consensus diagnostic criteria with standardized testing tools and for the identification and validation of objective markers of AOS. Additionally, these findings underscore the need for a training protocol if diagnostic tools are to be effective when shared beyond the research teams that develop and test them and disseminated to practicing speech-language pathologists, in order to ensure consistent application. [ABSTRACT FROM AUTHOR]

Background: Mild cognitive impairment (MCI) has an uncertain etiology and prognosis and may be challenging for clinicians to discuss with patients and families. Amyloid imaging may aid specialists in determining MCI etiology and prognosis, but creates novel challenges related to disease labeling. Methods: We convened a workgroup to formulate recommendations for clinicians providing care to MCI patients. Results: Clinicians should use the MCI diagnosis to validate patient and family concerns and educate them that the patient's cognitive impairment is not normal for his or her age and education level. The MCI diagnosis should not be used to avoid delivering a diagnosis of dementia. For patients who meet Appropriate Use Criteria after standard-of-care clinical workup, amyloid imaging may position specialists to offer more information about etiology and prognosis. Clinicians must set appropriate expectations, including ensuring that patients and families understand the limitations of amyloid imaging. Communication of negative results should include that patients remain at elevated risk for dementia and that negative scans do not indicate a specific diagnosis or signify brain health. Positive amyloid imaging results should elicit further monitoring and conversations about appropriate advance planning. Clinicians should offer written summaries, including referral to appropriate social services. Conclusions: In patients with MCI, there is a need to devote considerable time and attention to patient education and shared decision-making. Amyloid imaging may be a tool to aid clinicians. Careful management of patient expectations and communication of scan results will be critical to the appropriate use of amyloid imaging information. [ABSTRACT FROM AUTHOR]

Background: The importance of connected speech analysis in the diagnosis and further classification of primary progressive aphasia (PPA) is becoming apparent. However, methodological inconsistencies in elicitation and analysis of speech samples hinder comparison of different laboratories' results. The recent recommendations for further classification of PPA have characterised three main variants, but we have demonstrated that a considerable proportion of patients do not conform to any of these, as their language deficits extend beyond those of a single syndromic variant (mixed PPA). This report is an attempt to characterise the language profiles of different non-semantic variants of PPA using a combination of connected speech analysis and standard neuropsychological tests. Aims: Our aims were (a) to assess the relative efficacy of semi-structured interviews and picture description tasks in revealing the important aspects of language deficit in our patient groups, (b) to document the language profile of a mixed PPA group for the first time, (c) to compare the patterns of speech abnormality in non-fluent variant and mixed PPA, relative to each other and to normal control participants, and (d) to identify those features of spontaneous speech decline that are frequent and tangible enough to be detected during clinical consultations. Methods & Procedures: Connected speech samples obtained from picture description and semi-structured interviews were analysed quantitatively and the outcomes were contrasted between the elicitation methods and among the participant groups. Due to a very small number of cases fulfilling criteria for logopaenic PPA, the speech of these patients was scrutinised individually. Outcomes & Results: Pair-wise comparisons of the two speech elicitation methods at a group level revealed only a partial concordance and greater sensitivity of semi-structured interviews in detecting different aspects of speech abnormality. At a group level there was a significant impairment in the morpho-syntactic aspects of connected speech in both non-fluent and mixed PPA. A statistically significant difference from controls was observed in the semantic measures of discourse only in the mixed PPA group. Clinically useful features that differentiate both non-fluent and mixed PPA groups from healthy volunteers were decreased speech rate, shorter utterances, fewer complex grammatical structures, lack of spontaneity, more non-sentential speech units (elliptical and abandoned units), more hesitation markers, and, to a lesser extent, more phonological errors and editing breaks. Conclusions: The combination of the present results with those from our previous report on semantic dementia that used the same methodology offers a quantitative detailed assessment of connected speech across the spectrum of PPA. [ABSTRACT FROM AUTHOR]

Background: Neurodegenerative syndromes are associated with varying degrees of language impairment. Connected speech analysis provides the most realistic measure of language function but its use has been restricted by operational constraints. Aims: In this prospective study we assessed the relative utility of a picture description task and a semi-structured interview in exposing the language decline in semantic dementia (SD) and typical mild Alzheimer's disease (AD), compared to each other and to healthy volunteers. Methods & Procedures: Our cohort comprised 16 patients with a clinical diagnosis of SD, 20 with mild typical AD, and 30 healthy participants. All speech samples were recorded during a face-to-face interview and were subjected to a well-controlled quantitative analysis. Outcomes & Results: Our results suggest that (a) the picture description task is more sensitive to abnormalities in the semantic measures, whereas the interviews are better at exposing morpho-syntactic deficits; (b) circumlocution is not, as has sometimes been claimed, a salient feature of speech in SD; (c) increases in the frequency of hesitation markers and of phonological and syntactic errors are prominent features of language decline in mild AD; and (d) a 150-word interview sample is adequate to provide a realistic reflection of language impairment. Conclusions: This study compared, for the first time, the two most commonly used methods of eliciting connected speech and documented many similarities in results from the two but also some salient differences in their sensitivity to specific aspects of language deficit. In addition, although replicating some aspects such as anomia, of what is already known about the language impairments in these two conditions, the study provides novel findings for both that could help clinicians in syndromic classification of anomic speech. [ABSTRACT FROM AUTHOR]

• Cognitive resilience is normal cognition despite dementia-related neuropathologies. • Cognitive resilience in the oldest-old (age 90+) is important due to high dementia risk. • We describe a 96-year-old man resilient to three dementia-related neuropathologies. • Education, activity, low comorbidities, late onset hypertension may be related to resilience. Cognitive resilience provides insights into maintaining good cognition despite dementia-related neuropathologic changes. It is of special interest in the oldest-old (age 90+) because age is the strongest risk factor for dementia. We describe the only participant of The 90+ Study , among 367 autopsies, who maintained normal cognition despite intermediate-high levels of 3 dementia-related neuropathologic changes, advanced age, and comorbidities associated with cognitive impairment. This man remained cognitively normal throughout 13 semi-annual study visits, last one being 4 months before his death at 96. His cognitive test scores remained around the 90th percentile for non–timed tests and declined from 90th to 50th percentile (significant for semantic fluency) for timed tests. He remained physically and cognitively active until death, despite extrapyramidal signs in the last year of life. Neuropathological examination revealed intermediate level of Alzheimer's disease neuropathologic change (Thal phase 5, Braak NFT stage IV, CERAD score 3), Lewy bodies and neurites in the olfactory bulb, brainstem and limbic areas (Braak PD stage 4), TDP-43 inclusions in the amygdala and hippocampus (LATE stage 2), and a microvascular lesion in putamen. This case demonstrates that cognitive impairment is not inevitable even in the oldest-old with mutltiple dementia-related neuropathologic changes. [ABSTRACT FROM AUTHOR]