bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neuropsychiatric symptoms in early onset Alzheimer's disease and frontotemporal dementia
Authors: Stojkovic Tanja , Mandic Stojmenovic Gorana , Stefanova Elka , Kostic Vladimir S. 
Published: December 2020

AbstractBackgroundHaving in mind a significant percentage of atypical presentations at disease onset (behavioral symptoms, depression, psychotic symptoms or non‐cognitive cognitive deficits), understanding clinical heterogeneity of early onset Alzheimer's disease (EOAD) and frontotemporal dementia (EOFTD) can improve early diagnosis and differentiation between these clinical entities.Our objective was to investigate the heterogeneity of neuropsychiatric symptoms (NPS) in EOAD and EOFTD spectrum.MethodTwo hundred and seven consecutive patients with EOAD and EOFTD spectrum, diagnosed according to the current clinical criteria, were recruited from the Neurology Clinic, Clinical Centre of Serbia. Sociodemographic and clinical characteristics were evaluated using a pre‐designed semi‐structured questionnaire while neuropsychiatric symptoms (NPS) were evaluated using Neuropsychiatric Inventory (NPI).ResultEOAD and EOFTD patients did not differ in age, age at disease onset, duration of the disease, gender and education. In comparison to EOAD, patients in the EOFTD spectrum expressed agitation, euphoria, apathy, disinhibition, irritability, aberrant motor behavior and dietary changes more frequently. EOFTD behavioral variant patients expressed apathy, aberrant motor behavior and disinhibition more often than patients with PPA, while in PPA anxiety was represented. In EOAD group total NPI score correlated with clinical dementia rating scale score. In the advanced stages of dementia, EOAD patients expressed agitation and irritability more frequently than at disease onset, while in advanced EOFTD agitation and aberrant motor behavior were more frequent than in the earlier stages of the disease. Amnestic and non‐amnestic presentation of EOAD did not differ in frequency on NPSConclusionNPS are a hallmark of behavioral variant of EOFTD and later stages of EOAD.
Frequency of consumption of food groups for patients with Alzheimer‐type dementia, before the diagnosis of the disease in a second‐level hospital in Guadalajara, Jalisco, Mexico, 2020
Authors: de los Ángeles Vargas‐Rodríguez María , Llamas‐López Leonardo 
Published: December 2020

AbstractBackgroundThe nutrients obtained through food and the interaction they present with the mechanisms of epigenetics point as a means of prevention and treatment for AD. The identification of food in each population is important considering that each one has aspects that make it unique. The realization of retrospective dietary surveys allows us to know how people's diet were and correlate the existence in the development of a pathology.MethodDescriptive, observational, retrospective design with mixed approach. With n=15 AD who assisted the service of neurology and n=15 control group, healthy older adults according to the WHO definition and the test modified MMSE (score of 16‐19 points). Both groups over 60 years.ResultTo statistically analyze X2 (p=<0.05) was used, in fig. 1 of the consumption of soda, it can be observed that the AD consumed soda more frequently. Regarding the consumption of vegetables such as nopal, tomato, chayote and consumption of fruits such as apples and bananas, it did not obtain statistical significance, but with guava it did have fig. 2 (p=0.019). The groups of cereals, legumes and dairy products were not statistically significant. While in foods of animal origin (red meat, white meat and egg) there was no statistical significance but it can be seen in fig. 3 as AD have a higher frequency of red meat (p=0.060). While statistical significance was found in the use of lard(p=0.048) being more frequent in the control group. Regarding lifestyle there was no significance. But we found significance in water consumption (p=0.013) and tobacco use (p=0.009).ConclusionWe can conclude that when looking at the data on food consumption, it seems that they play a role in the development of the disease, not reflecting it statistically, probably due to the small sample that was used. The suspicions of various authors point to a higher consumption of simple carbohydrates, reflected in our study in fig. 1. While the importance of water consumption was demonstrated in our study, the recommended consumption is 2,000 ml, the control group consumed it closer to this amount and tobacco use was of great importance, highlighting greater use in AD.
The epidemiology of the different clinical presentations of early onset dementia
Authors: Chiari Annalisa , Adani Giorgia , Vinceti Giulia , Tondelli Manuela , Galli Chiara , Fiondella Luigi , Costa Manuela , Molinari Maria Angela , Filippini Tommaso , Vinceti Marco , Zamboni Giovanna 
Published: December 2020

AbstractBackgroundIt is known that patients with Early Onset Dementia (EOD), defined as dementia with symptoms onset before the age of 65, frequently present with atypical clinical syndromes. However, the epidemiology of the different presentations of EOD, including the clinical variants of Alzheimer’s dementia (AD) and frontotemporal dementia (FTD), has never been investigated altogether in the same population‐based study, probably because their characterisation is relatively recent, and subsequent to the advent of AD biomarkers. Epidemiologic data on all‐causes of EOD are also scarce, inconsistent, and mostly based on low‐level clinical assessment.MethodWe investigated the epidemiology of EOD in the province of Modena, Northern Italy (700,000 inhabitants), by identifying newly‐diagnosed EOD patients retrospectively from January 2006 to December 2016, and prospectively from January 2017 to June 2019. Diagnosis was based on extended clinical and neuropsychological assessment, and supported by the use of imaging and cerebrospinal fluid biomarkers in the majority of cases.ResultEOD age‐ and sex‐adjusted incidence was 6.45/100000 inhabitants/year during the 2016‐2019 period, corresponding to 46 new cases per year in the overall study population. At census day (30th June 2019), there were 258 patients with a clinical diagnosis of EOD (123 males) in the province of Modena. Crude Prevalence was 74.3/100000 (71.2 in males and 77.4 in females) in the population aged 30‐64, and 119.9/100000 (117.1 in males and 122.6 in females) in the population aged 45‐64. Overall crude prevalence was 36.4/100000 inhabitants (35.5/100000 in males, 37.4/100000 in females). The most frequent EOD was the amnestic variant of AD (crude incidence of 21.6/100000 and prevalence of 5/100000 persons aged 30‐64 years), followed by the behavioural variant of FTD (crude incidence of 14.1/100000 and prevalence of 2.8/100000 persons aged 30‐64 years), and logopenic variant of primary progressive aphasia (crude incidence of 5.8/100000 and prevalence of 0.8/100000 persons aged 30‐64 years).ConclusionWe provide the first report on incidence and prevalence of all the clinical presentations of EOD including different variants of AD and FTD. These epidemiological data will benefit the clinical reasoning of clinicians faced with dementia in young patients and will allow to improve dementia care organisation.
Language changes in Alzheimer's disease in a patient of the Karajá ethnicity
Authors: de Lacerda Maria Carolina Cabral , Caixeta Leonardo Ferreira 
Published: December 2020

AbstractBackgroundThe influence of an ethnic role in the expression of (AD) alzheimer's disease has been studied by several authors. However, there are practically no studies on mental health in the indigenous elderly.MethodA male patient, 72 years old, chief of the Karajá indigenous tribe, with a medical diagnosis of Alzheimer's Disease, with language disorders was evaluated both in Portuguese and in the native language Karajá. Was used the Boston Naming Test (BNT), Verbal fluency (semantic category) and board Theft of biscuits. Ten target figures were also used, referring to their natural habitat (turtle, pipes, arrow, gourd, jaguar, fire, banana tree, drum, net and hollow).ResultThe results demonstrated that there is a deterioration of the language in both evaluated languages, worse in Portuguese. In the Boston naming test, of the 60 named figures, the patient named figures in 21 Portuguese language and 28 Karajá linguage figures. In verbal fluency he presented 05 words in Portuguese and 07 in Karajá. In oral production, he demonstrated important anomie, an empty speech with little context, in both languages. Regarding the target figures of their habitat, he showed anomie to a figure (drum) in Karajá, "Weriri".ConclusionFurther studies aimed at investigating language disorders in different ethnic groups, especially indigenous peoples, allow for early diagnosis of dementia, as well as assisting public policies on quality of life and mental health in this community.
3xTg Alzheimer’s disease mice are more susceptible to induced seizures
Authors: Vyver Maxime Vande , De Bundel Dimitri , Nagels Guy , Engelborghs Sebastiaan , Smolders Ilse 
Published: December 2020

AbstractBackgroundEpilepsy is a frequent comorbidity in patients with Alzheimer’s disease (AD).1 Early cellular hyperexcitability and seizures are present in several AD mouse models.2,3 The mechanisms responsible for these changes in excitability, the impact on the disease and how they could be reversed remain largely unknown.MethodWe used the triple‐transgenic (3xTg) mouse model, that has mutations affecting the two main proteins involved in AD: amyloid and tau. Seven‐week‐old female 3xTg (n = 19) and age‐ and gender‐matched wild‐type (n = 19) mice were corneally kindled with the 6 Hz electrical stimulations.4 Corneal kindling is a model of repeated induced seizures, where identical electric stimuli applied to the eyes, give rise to a progressive seizure phenotype. Once a mouse was fully kindled (defined as 10 consecutive generalized seizures), it was treated with several antiseizures drugs (ASDs) to assess their effect. Spontaneous locomotor activity and anxiety‐like behavior was tested with open field. After the experiments, mice were killed and brains were evaluated for amyloid and tau pathology with (immuno)histochemistry.ResultWhen subjected to identical stimuli 3xTg mice exhibit more severe seizures compared to wild‐type mice (p < 0.001). This difference is most prominent in the beginning of the kindling process and reduces over time (p < 0.001). Levetiracam and brivaracetam have similar efficacy in reducing seizure severity, lamotrigine is less effective. Seizures in 3xTg mice are more resistant to the three tested ASDs in comparison to wild‐type mice (p < 0.01). Despite being more active during handling after several weeks of corneal kindling, no increased spontaneous locomotor activity nor anxiety‐like behavior was detected in 3xTg mice.ConclusionThe presence of alterations in both amyloid and tau pathways results in an increase in seizure susceptibility at young age, before neurofibrillary tangles or amyloid plaques are expected to be present. The seizures of the 3xTg mice are more resistant to clinically used ASDs. The 6 Hz corneal kindling in mice is increasingly established as a model of epileptogenesis and an accessible model to assess seizure susceptibility and ASD effect in fully kindled AD mice. References: (1) Subota, 2017. (2) Vossel, 2017. (3) Palop, 2016. (4) Leclercq, 2014.
Brain iron burden is associated with accelerated cognitive decline in Alzheimer’s disease
Authors: Ayton Scott , Portbury Stuart , Kalinowski Pawel , Diouf Ibrahima , Agarwal Puja , Schneider Julie A. , Morris Martha Clare , Bush Ashley I. 
Published: December 2020

AbstractBackgroundBrain iron has been reported elevated in Alzheimer’s disease (AD) in mostly small studies that were without extensive clinicopathological classification. Brain iron may be important for disease progression since it can become pro‐oxidant and induce cell death (by ferroptosis) or inflammation (by promoting an inflammatory phenotype of microglia). Here, we report the largest post‐mortem study of brain iron in AD, examining iron in multiple brain regions in a large (645) group across the clinicopathological staging of the disease with extensive cognitive data collected in the decade prior to death.MethodsIron was measured in gray matter from inferior temporal, mid frontal, anterior cingulate, and cerebellar cortices from 645 post‐mortem brains (Memory and Aging Project). AD pathology was defined by CERAD criteria. NINCDS‐ADRDA criteria were used to assign AD clinical diagnosis during life. Cognitive performance (test batteries for multiple cognitive domains) was assessed annually in the decade prior to death. Analysis consisted of mixed‐effects models with quadratic and linear variables: iron, age, sex, APOE ε4, plaque counts, neurofibrillary tangle counts, Lewy bodies, vascular infarcts.ResultsThis study included 166 pathology‐negative subjects without dementia, 40 pathology‐negative subjects with dementia, 212 subjects with AD pathology but without dementia, and 227 subjects with AD pathology and dementia. In subjects without dementia, iron levels were not associated with pathological status, demonstrating that iron does not elevate in the brain merely with increasing pathology load. Iron was elevated (p = 2 × 10−4) in the inferior temporal cortex of people with AD pathology and clinical dementia, but not in any other region. Nonetheless, the iron status of each region was strongly associated with accelerated cognitive decline in the years prior to death, regardless of whether iron was increased, with a composite of iron values in each region demonstrating the greatest performance (Figure 1).ConclusionsIron is regionally elevated in AD brains, but, importantly, iron need not be increased to pathological levels to influence neurodegeneration. Rather, iron burden acts as a risk factor trait in brains with iron levels in the normal range.
Hyperspectral retinal imaging shows amyloid‐like deposits in preclinical Alzheimer’s disease
Authors: Shah Tejal M. , Gupta Sunil M. , Goozee Kathryn , Chatterjee Pratishtha , Sohrabi Hamid , Martins Ralph N. 
Published: December 2020

AbstractBackgroundBrain beta‐amyloid deposits in Alzheimer’s disease (AD) are associated with retinal beta‐amyloid deposits post‐mortem, yet, findings from imaging the live human retina provide inconclusive evidence due to confounding factors such as drusen found in age‐related macular degeneration [(AMD), (Kayabasi 2014, Koronyo‐Hamaoui 2017)]. We therefore aimed to identify drusen and retinal amyloid‐like deposits via hyperspectral imaging.MethodCognitively normal (n=45) older adults, aged 50‐85 years with known neocortical amyloid burden (NAB) including those at‐risk for AD (SUVR≥1.35), were recruited from our study cohorts in Sydney, New South Wales. All participants completed imaging in the spectral range of 450 to 900nm wavelength at 5nm steps. 11 participants completed optical coherence tomography to confirm presence/absence of drusen. Raw hyperspectral images were visually scanned to identify retinal deposits.ResultMatched to our reference images, we identified retinal hyperintense ‘nano dots’. The spectral range of drusen and nano dots was between 500 to 635 nm and 450 to 600 nm respectively. Drusen was more around the macula in a clustered fashion. nano dots were seen in abundance in the superior quadrant, scattered along the blood vessels and appeared smaller with well distinct margin. In participants with no history of AMD (n=30), the visual identification of nano dots was possible for 77% in high NAB and no nanodots were visually identified in 70% in low NAB group participants.ConclusionFurther investigation is required to examine the nano dots to determine whether they have diagnostic significance.
Cognitive training for people with dementia: A Cochrane review
Authors: Bahar‐Fuchs Alex , Martyr Anthony , Goh Anita M Y , Sabates Julieta M , Clare Linda 
Published: December 2020

AbstractBackgroundCognitive training (CT) has been found by previous reviews to be ineffective in relation to cognitive and non‐cognitive outcomes among people with neurodegenerative or vascular dementias (Bahar‐Fuchs et al. 2013). However, the quality of trials has been regarded as low, and numerous new trials have been completed in recent years. Here we present findings of a comprehensive update to this review (Bahar‐Fuchs et al. 2019).Methods33 RCTs were eligible for inclusion, 11 of which were included in our 2013 review. Study characteristics and data required for effect size calculations were extracted and Risk of Bias for each study was rated in duplicate. Change from baseline was used to calculate effect estimates (Hedges g), and a random effects meta‐analysis was performed, including investigation of effect moderators. Quality of evidence was evaluated using GRADE.ResultsFigure 1 summarizes risk of bias in various domains. We found moderate quality evidence of a small‐moderate effect of CT relative to control on the primary outcome, global cognition immediately following treatment (SMD=0.42, CI=0.23‐0.62, Figure 2), which was maintained at a medium‐term follow‐up. None of our pre‐specified factors moderated this effect. We also found high‐quality evidence of a moderate effect of CT on verbal semantic fluency (SMD 0.52, 95% CI 0.23‐0.81) at end of treatment, which was maintained in the medium term. No benefits of CT where found compared with an alternative treatment, and the quality of evidence in relation to most other outcomes was low, so we could not determine whether it was associated with meaningful benefits.ConclusionsThis comprehensive updated review suggests, for the first time, that CT is associated with a small to moderate effect on global cognition and semantic fluency in people with mild‐moderate dementia. quality of evidence remains an issue, and confidence in the findings in relation to many meaningful outcomes remains low. References: Bahar‐Fuchs, A., et al. (2013). Cognitive training and cognitive rehabilitation for mild to moderate Alzheimer's disease and vascular dementia. Cochrane Database of Systematic Reviews, Issue 6. Bahar‐Fuchs A, et al. (2019). Cognitive training for people with mild to moderate dementia. Cochrane Database of Systematic Reviews. 2019(3).
Rates of amyloid PET positivity in geriatric HIV
Authors: Milanini Benedetta , Javandel Shireen , Hillis Madeline , Chen Karen , Hellmuth Joanna , Paul Robert , Pohl Kilian M , Valcour Victor 
Published: December 2020

AbstractBackgroundChronic HIV infection and amyloid deposition with aging may represent a double‐hit to the brain. We aimed to define the rate of amyloid positivity among older HIV‐infected adults and contrast the demographic, clinical and neuropsychological features of HIV+ amyloid PET+ individuals compared to HIV+ amyloid PET‐ participants.MethodStudy sample included 52 adults with chronic HIV infection. Participants underwent a standardized neurological and neuropsychological assessment that tapped multiple cognitive domains. HIV diagnostic criteria informed by clinical acumen were applied to diagnose HIV‐associated neurocognitive disorder. None of the participants showed a clinical picture consistent with Alzheimer’s disease (AD). Florbetapir amyloid PET scans were read by trained and certified neurologists as positive (n=5) or negative (n=47) (Johnson et al., 2013). T‐tests and chi‐squared tests were performed to explore differences between the two groups.ResultWe found 10% rate of amyloid positivity in our cohort. The PET‐ and PET+ groups were similar in age, sex and education. The mean (SD; range) age was 67 (5; 60‐86) for PET‐ and 69 (5; 63‐73) for PET+ participants. All participants but two were male (PET‐: 45 (96%); PET+: 5 (100%)). The mean (SD) education was 16 (2) for both groups. No differences were found in clinical HIV‐related variables. For PET‐ participants, mean (SD) nadir and current CD4 count were 165 (126) and 574 (275) versus 188 (116) and 620 (180) in the PET+ group. All participants were on antiretroviral treatment with undetectable HIV RNA in plasma. Cognitively, all participants presented with mild neurocognitive disorder and the two groups performed similarly in all the cognitive domains explored, including memory.ConclusionResults reveal a low frequency of amyloid positivity among virally suppressed HIV‐infected individuals over the age of 60, similar to that published among the age‐matched seronegative population (i.e., 12%), suggesting that HIV does not link to a higher amyloid plaque burden. Moreover, older HIV‐infected individuals classified as amyloid positive exhibit a similar profile as their amyloid negative counterparts. While we did not observe an increased amyloid deposition by using PET, further studies are needed to determine if amyloid PET is an effective tool for identifying AD in the setting of HIV.
Reduction of lipid peroxidase levels in EFAD mouse model
Authors: Cacciottolo Mafalda , Thorwald Max A. , Forman Henry J. , Morgan Todd E. , Finch Caleb E. 
Published: December 2020

AbstractBackgroundCerebral microbleeds (MBs) are more prevalent in APOE4 carriers and associated with Alzheimer Disease (AD). Loss of cerebrovascular integrity, blood‐brain barrier breakdown, and reduced Aβ clearance are also shown by APOE4 carrier mice. In AD, increased brain amyloid coupled with increased oxidative stress may synergistically contribute to MBs prevalence. EFAD mice carrying familial dominant AD genes in combination with human apoE alleles are a model for sex differences in AD, with greater amyloid accumulation and microbleeds in female E4FAD mice.Independently, Aβ and heme from microbleeds contribute to increased oxidative stress. New data suggest increased lipid peroxidation in E4 mice at baseline as measured by 4‐HNE. Peroxiredoxin 6 (Prdx6) and glutathione peroxidase 4 (GPx4) are the only known antioxidant enzymes capable of detoxifying oxidized phospholipids.MethodPrdx6 and GPx4 were studied by Western blot in cortical lysates of 6mo old EFAD mice. To evaluate Aβ contribution, we analyzed Prdx6 and GPx4 in 2mo old EFAD mice, which show 2 to 10‐fold lower Aβ compared to 6mo EFAD mice, and 6mo old EFAD non carrier siblings (no AD‐transgene).ResultPrdx6 was decreased in E4FAD mice (M: ‐30%; F: ‐50%) compared to E3FAD mice. GPx4 was decreased only n E4FAD females (M: no change; F: ‐50%). Younger mice did not show differences in either lipid peroxidases at 2mo. Interestingly, Prdx6 but not GPx4 was reduced in 6mo old female E4FAD non carrier siblings.ConclusionOur data suggest that the decreased levels of Prdx6 in 6mo old female E4 carrier mice in absence of Aβ might impair their ability to reduce oxidized lipids and predispose them to membrane alteration. Moreover, aging and increase of Aβ load together might contribute to the reduction of GPx4 levels in APOE4 carriers and the accumulation of MBs. Additional studies are required to clarify the underlying interaction sex‐apoE allele in MBs onset and its contribution to the pathogenesis of AD.