The Effect of Motivation on Movement: A Study of Bradykinesia in Parkinson’s Disease

Background

Bradykinesia is a cardinal feature of Parkinson’s disease (PD). Despite its disabling impact, the precise cause of this symptom remains elusive. Recent thinking suggests that bradykinesia may be more than simply a manifestation of motor slowness, and may in part reflect a specific deficit in the operation of motivational vigour in the striatum. In this paper we test the hypothesis that movement time in PD can be modulated by the specific nature of the motivational salience of possible action-outcomes.

Methodology/Principal Findings

We developed a novel movement time paradigm involving winnable rewards and avoidable painful electrical stimuli. The faster the subjects performed an action the more likely they were to win money (in appetitive blocks) or to avoid a painful shock (in aversive blocks). We compared PD patients when OFF dopaminergic medication with controls. Our key finding is that PD patients OFF dopaminergic medication move faster to avoid aversive outcomes (painful electric shocks) than to reap rewarding outcomes (winning money) and, unlike controls, do not speed up in the current trial having failed to win money in the previous one. We also demonstrate that sensitivity to distracting stimuli is valence specific.

Conclusions/Significance

We suggest this pattern of results can be explained in terms of low dopamine levels in the Parkinsonian state leading to an insensitivity to appetitive outcomes, and thus an inability to modulate movement speed in the face of rewards. By comparison, sensitivity to aversive stimuli is relatively spared. Our findings point to a rarely described property of bradykinesia in PD, namely its selective regulation by everyday outcomes.     

Emotion Processing in Parkinson’s Disease: A Three-Level Study on Recognition,Representation, and Regulation

Background

Parkinson’s disease (PD) is characterised by well-known motor symptoms, whereas the presence of cognitive non-motor symptoms, such as emotional disturbances, is still underestimated. One of the major problems in studying emotion deficits in PD is an atomising approach that does not take into account different levels of emotion elaboration. Our study addressed the question of whether people with PD exhibit difficulties in one or more specific dimensions of emotion processing, investigating three different levels of analyses, that is, recognition, representation, and regulation.

Methodology

Thirty-two consecutive medicated patients with PD and 25 healthy controls were enrolled in the study. Participants performed a three-level analysis assessment of emotional processing using quantitative standardised emotional tasks: the Ekman 60-Faces for emotion recognition, the full 36-item version of the Reading the Mind in the Eyes (RME) for emotion representation, and the 20-item Toronto Alexithymia Scale (TAS-20) for emotion regulation.

Principal Findings

Regarding emotion recognition, patients obtained significantly worse scores than controls in the total score of Ekman 60-Faces but not in any other basic emotions. For emotion representation, patients obtained significantly worse scores than controls in the RME experimental score but no in the RME gender control task. Finally, on emotion regulation, PD and controls did not perform differently at TAS-20 and no specific differences were found on TAS-20 subscales. The PD impairments on emotion recognition and representation do not correlate with dopamine therapy, disease severity, or with the duration of illness. These results are independent from other cognitive processes, such as global cognitive status and executive function, or from psychiatric status, such as depression, anxiety or apathy.

Conclusions

These results may contribute to better understanding of the emotional problems that are often seen in patients with PD and the measures used to test these problems, in particular on the use of different versions of the RME task.     

Study on the Effect of Kidney Transplantation on the Health of the Patients’ Offspring: A Report on 252 Chinese Children

Even though the incidence of pregnancies in the female recipients is lower and also chronic renal disease in male patients is associated with impaired spermatogenesis, the health of the children born to these patients was not studied. In this report, we discuss information on the growth and development of offspring of 248 male and female kidney recipient patients. Physical and routine clinical measurements of the 252 offspring (129 male and 123 female) born to these transplantation patients were made along with the intelligence tests. In some of these children chest X-ray and immune indices were assessed. Among the recipients, 219 males fathered 223 children with an average birth weight of 3,255 ± 374 g and 29 female recipients gave birth to 29 children with an average birth weight of 2,923 ± 551. While most of these children were normal, we noticed a case of soft double toe, a case of short tongue tie, five cases of marginal mental retardation, three cases of proteinuria, six cases of microscopic hematuria, 15 cases of low hemoglobin, and 21 cases with recurrent respiratory tract infections. We conclude that kidney transplantation has no significant impact on the growth, development, health, and intelligence of the offspring born to recipients.     

Parrondo’s Games Based on Complex Networks and the Paradoxical Effect

Parrondo’s games were first constructed using a simple tossing scenario, which demonstrates the following paradoxical situation: in sequences of games, a winning expectation may be obtained by playing the games in a random order, although each game (game A or game B) in the sequence may result in losing when played individually. The available Parrondo’s games based on the spatial niche (the neighboring environment) are applied in the regular networks. The neighbors of each node are the same in the regular graphs, whereas they are different in the complex networks. Here, Parrondo’s model based on complex networks is proposed, and a structure of game B applied in arbitrary topologies is constructed. The results confirm that Parrondo’s paradox occurs. Moreover, the size of the region of the parameter space that elicits Parrondo’s paradox depends on the heterogeneity of the degree distributions of the networks. The higher heterogeneity yields a larger region of the parameter space where the strong paradox occurs. In addition, we use scale-free networks to show that the network size has no significant influence on the region of the parameter space where the strong or weak Parrondo’s paradox occurs. The region of the parameter space where the strong Parrondo’s paradox occurs reduces slightly when the average degree of the network increases.     

Diabetes Mellitus and the Risk of Alzheimer’s Disease: A Nationwide Population-Based Study

Objectives

Possible association between diabetes mellitus (DM) and Alzheimer’s disease (AD) has been controversial. This study used a nationwide population-based dataset to investigate the relationship between DM and subsequent AD incidence.

Methods

Data were collected from Taiwan’s National Health Insurance Research Database, which released a cohort dataset of 1,000,000 randomly sampled people and confirmed it to be representative of the Taiwanese population. We identified 71,433 patients newly diagnosed with diabetes (age 58.74±14.02 years) since January 1997. Using propensity score, we matched them with 71,311 non-diabetic subjects by time of enrollment, age, gender, hypertension, hyperlipidemia, and previous stroke history. All the patients were followed up to December 31, 2007. The endpoint of the study was occurrence of AD.

Results

Over a maximum 11 years of follow-up, diabetic patients experienced a higher incidence of AD than non-diabetic subjects (0.48% vs. 0.37%, p<0.001). After Cox proportional hazard regression model analysis, DM (hazard ratio [HR], 1.76; 95% confidence interval [CI], 1.50–2.07, p<0.001), age (HR, 1.11; 95% CI, 1.10–1.12, p<0.001), female gender (HR, 1.24; 95% CI, 1.06–1.46, p = 0.008), hypertension (HR, 1.30; 95% CI, 1.07–1.59, p = 0.01), previous stroke history (HR, 1.79; 95% CI, 1.28–2.50, p<0.001), and urbanization status (metropolis, HR, 1.32; 95% CI, 1.07–1.63, p = 0.009) were independently associated with the increased risk of AD. Neither monotherapy nor combination therapy with oral antidiabetic medications were associated with the risk of AD after adjusting for underlying risk factors and the duration of DM since diagnosis. However, combination therapy with insulin was found to be associated with greater risk of AD (HR, 2.17; 95% CI, 1.04–4.52, p = 0.039).

Conclusion

Newly diagnosed DM was associated with increased risk of AD. Use of hypoglycemic agents did not ameliorate the risk.     

Association between APOC1 Polymorphism and Alzheimer’s Disease: A Case-Control Study and Meta-Analysis

Background

Previous association studies examining the relationship between the APOC1 polymorphism and susceptibility to Alzheimer’s disease (AD) have shown conflicting results, and it is not clear if an APOC1 variant acts as a genetic risk factor in AD etiology across multiple populations.

Methods

To confirm the risk association between APOC1 and AD, we designed a case-control study and also performed a meta-analysis of previously published studies.

Results

Seventy-nine patients with AD and one hundred fifty-six unrelated controls were included in case-control study. No association was found between the variation of APOC1 and AD in stage 1 of our study. However, our meta-analysis pooled a total of 2092 AD patients and 2685 controls. The APOC1 rs11568822 polymorphism was associated with increased AD risk in Caucasians, Asians and Caribbean Hispanics, but not in African Americans. APOE ε4 carriers harboring the APOC1 insertion allele, were more prevalent in AD patients than controls (χ² = 119.46, OR = 2.79, 95% CI = 2.31–3.36, P<0.01).

Conclusions

The APOC1 insertion allele, in combination with APOE ε4, likely serves as a potential risk factor for developing AD.     

Effect of BDNF Val66Met on Memory Decline and Hippocampal Atrophy in Prodromal Alzheimer’s Disease: A Preliminary Study

Objective

Cross-sectional genetic association studies have reported equivocal results on the relationship between the brain-derived neurotrophic factor (BDNF) Val66Met and risk of Alzheimer’s disease (AD). As AD is a neurodegenerative disease, genetic influences may become clearer from prospective study. We aimed to determine whether BDNF Val66Met polymorphism influences changes in memory performance, hippocampal volume, and Aβ accumulation in adults with amnestic mild cognitive impairment (aMCI) and high Aβ.

Methods

Thirty-four adults with aMCI were recruited from the Australian, Imaging, Biomarkers and Lifestyle (AIBL) Study. Participants underwent PiB-PET and structural MRI neuroimaging, neuropsychological assessments and BDNF genotyping at baseline, 18 month, and 36 month assessments.

Results

In individuals with aMCI and high Aβ, Met carriers showed significant and large decline in episodic memory (d = 0.90, p = .020) and hippocampal volume (d = 0.98, p = .035). BDNF Val66Met was unrelated to the rate of Aβ accumulation (d = −0.35, p = .401).

Conclusions

Although preliminary due to the small sample size, results of this study suggest that high Aβ levels and Met carriage may be useful prognostic markers of accelerated decline in episodic memory, and reductions in hippocampal volume in individuals in the prodromal or MCI stage of AD.     

Estimating the Effect of Intimate Partner Violence on Women’s Use of Contraception: A Systematic Review and Meta-Analysis

BackgroundIntimate partner violence (IPV) is an important global public health problem. While there is a growing literature on the association between IPV and women’s reproductive health (RH) outcomes, most studies are cross-sectional—which weakens inference about the causal effect of IPV on women’s RH. This systematic review synthesizes existing evidence from the strongest study designs to estimate the impact of IPV on women’s use of contraception.MethodsWe searched 11 electronic databases from January of 1980 to 3 December 2013 and reviewed reference lists from systematic reviews for studies examining IPV and contraceptive use. To be able to infer causality, we limited our review to studies that had longitudinal measures of either IPV or women’s use of contraception.ResultsOf the 1,574 articles identified by the search, we included 179 articles in the full text review and extracted data from 12 studies that met our inclusion criteria. We limited the meta-analysis to seven studies that could be classified as subject to low or moderate levels of bias. Women’s experience of IPV was associated with a significant reduction in the odds of using contraception (n = 14,866; OR: 0.47; 95% CI: 0.25, 0.85; I² = 92%; 95% CI_I²: 87%, 96%). Restricting to studies that measured the effect of IPV on women’s use of partner dependent contraceptive methods was associated with a reduction in the heterogeneity of the overall estimate. In the three studies that examined women’s likelihood of using male condoms with their partners, experience of IPV was associated with a significant decrease in condom use (OR: 0.48; 95% CI_OR: 0.32, 0.72; I² = 51%; 95% CI_I²: 0%, 86%).ConclusionsIPV is associated with a reduction in women’s use of contraception; women who experience IPV are less likely to report using condoms with their male partners. Family planning and HIV prevention programs should consider women’s experiences of IPV.     

Digitomotography in Parkinson’s Disease: A Cross-Sectional and Longitudinal Study

Motor symptoms in Parkinson’s disease (PD) are usually assessed with semi-quantitative tests such as the Unified PD Rating Scale (UPDRS) which are limited by subjectivity, categorical design, and low sensitivity. Particularly bradykinesia as assessed e.g. with speeded index finger tapping exhibits low validity measures. This exploratory study set out to (i) assess whether force transducer-based objective and quantitative analysis of motor coordination in index finger tapping is able to distinguish between PD patients and controls, and (ii) assess longitudinal changes. Sixteen early-stage and 17 mid-stage PD patients as well as 18 controls were included in the cross-sectional part of the study; thirteen, 16 and 16 individuals of the respective groups agreed in a reassessment 12 months later. Frequency, force, rhythmicity, regularity and laterality of speeded and metronome paced tapping were recorded by digitomotography using a quantitative motor system ("Q-Motor"). Analysis of cross-sectional data revealed most consistent differences between PD patients and controls in variability of tap performance across modalities assessed. Among PD patients, variability of taps and the ability to keep a given rhythm were associated with UPDRS motor and finger tapping scores. After 12 months, laterality parameters were reduced but no other parameters changed significantly. This data suggests that digitomotography provides quantitative and objective measures capable to differentiate PD from non-PD in a small cohort, however, the value of the assessment to track PD progression has to be further evaluated in larger cohorts of patients.     

A 1H and 13C NMR Study on the Role of Salt-Bridges in the Formation of a Type I β-Turn in N-Acetyl-L-Asp-L-Glu-L-Lys-L-Ser-NH2

Abstract

The conformation of the tetrapeptide N-Acetyl-Asp⁷-Glu⁸-Lys⁹-Ser¹⁰-NH₂, a fragment of the type I collagen α-1 chain N-telopeptide, has been studied by ¹H and ¹³C NMR and circular dichroism spectroscopy. The spectroscopic evidence, based on two-dimensional, phase-sensitive NMR techniques such as COSY, ROESY, proton-carbon shift correlation and selective COLOC, indicates a strong dependence of the conformation on the experimental conditions. In CD₃OH/H₂O (60/40) at ca. neutral pH the tetrapeptide forms a β-turn, stabilized by a hydrogen bond between NH(S¹⁰) and CO(D⁷) and a strong salt-bridge between COO^?(E⁸) and NH₃ ⁺(K⁹). The β-turn is type I and appears to coexist with a non-hydrogen-bonded structure. The coexistence of these two conformers is proven by proton NMR data such as NH-NH ROEs, reduced NH-H_α(E⁸) coupling constant NH(E⁸) low-field shift and the temperature coefficient of NH(S¹⁰), whereas the conclusion regarding the salt-bridge is based on ¹³C results. In the same solvent, at a pH below the pKa of the carboxyl groups, no evidence for a conformation other than extended can be found. In aqueous solution at approximately neutral pH, evidence for the E⁸-K⁹ charge interaction is observed, but not for a hydrogen bond anywhere in the molecule.     

Recent advances in stem cells therapy: A focus on cancer,Parkinson’s and Alzheimer’s

Stem cells serve as potential therapeutics due to their high proliferative capacity, low immunogenic reactivity and their differentiating capabilities. Several pre-clinical and early-stage clinical studies are carried out to treat genetic diseases, cancers and neurodegenerative disorders with promising preliminary results. However, there are still many challenges that scientists are trying to overcome such as the unclear expression profile of stem cells in vivo, the homing of stem cells to the site of injury and their potential immune-reactivity. Prospective research lies in gene editing of autologous stem cells in vitro and safe injection of these modified cells back into patients. Here, we review the clinical trials executed using stem cell therapy in an attempt to cure challenging diseases like cancer, Parkinson’s and Alzheimer’s diseases.     

Effect of Ethiopia’s Health Extension Program on Maternal and Newborn Health Care Practices in 101 Rural Districts: A Dose-Response Study

Background

Improving newborn survival is essential if Ethiopia is to achieve Millennium Development Goal 4. The national Health Extension Program (HEP) includes community-based newborn survival interventions. We report the effect of these interventions on changes in maternal and newborn health care practices between 2008 and 2010 in 101 districts, comprising 11.6 million people, or 16% of Ethiopia’s population.

Methods and Findings

Using data from cross-sectional surveys in December 2008 and December 2010 from a representative sample of 117 communities (kebeles), we estimated the prevalence of maternal and newborn care practices, and a program intensity score in each community. Women with children aged 0 to 11 months reported care practices for their most recent pregnancy and childbirth. The program intensity score ranged between zero and ten and was derived from four outreach activities of the HEP front-line health workers. Dose-response relationships between changes in program intensity and the changes in maternal and newborn health were investigated using regression methods, controlling for secular trend, respondents’ background characteristics, and community-level factors.Between 2008 and 2010, median program intensity score increased 2.4-fold. For every unit increase in the score, the odds of receiving antenatal care increased by 1.13 times (95% CI 1.03–1.23); the odds of birth preparedness increased by 1.31 times (1.19–1.44); the odds of receiving postnatal care increased by 1.60 times (1.34–1.91); and the odds of initiating breastfeeding immediately after birth increased by 1.10 times (1.02–1.20). Program intensity score was not associated with skilled deliveries, nor with some of the other newborn health care indicators.

Conclusions

The results of our analysis suggest that Ethiopia’s HEP platform has improved maternal and newborn health care practices at scale. However, implementation research will be required to address the maternal and newborn care practices that were not influenced by the HEP outreach activities.     

A Comparative Study of the Oxidative Profile in Graves’ Disease, Hashimoto’s Thyroiditis, and Papillary Thyroid Cancer

The aim of this study was to evaluate and compare the oxidative profiles of three thyroid disorders: Graves’ disease (GD), Hashimoto thyroiditis (HT), and papillary thyroid cancer (PTC). Malondialdehyde levels (MDA), glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) activities were examined in the plasma of 52 patients (29 untreated HT, 16 untreated GD, and 7 PTC who underwent surgical therapy). Results were compared with those of 30 healthy controls and among the three groups of patients. The GD, HT, and PTC patients exhibited increased plasma MDA levels and SOD activities compared with the controls (p?<?0.05, p?<?0.05, and p?<?0.001, respectively). CAT activities significantly increased only for the PTC and HT patients (p?<?0.001 and p?<?0.05, respectively), whereas GPx activities significantly decreased only in the GD and PTC (p?<?0.05 and p?<?0.01, respectively). The comparison among the three groups of patients has shown increased MDA level and SOD activity for the PTC patients as compared to the GD patients (p?<?0.01 and p?<?0.001, respectively). Compared with HT, PTC patients exhibited significant higher MDA level, SOD, and CAT activities and a significant lower GPx activity (p?<?0.01, p?<?0.001, p?<?0.05, and p?<?0.05, respectively). No significant discrepancies were noted between the GD and HT patients. Our results have clearly shown an oxidative profile that is highly disturbed for the PTC patients as compared to those of autoimmune disorders. Future studies are needed to determine whether or not the oxidative stress has a prognostic value in this pathology.     

Effect of glucose on Listeria monocytogenes biofilm formation,and assessment of the biofilm’s sanitation tolerance

Listeria monocytogenes is an important cause of human foodborne infections and its ability to form biofilms is a serious concern to the food industry. To reveal the effect of glucose conditions on biofilm formation of L. monocytogenes, 20 strains were investigated under three glucose conditions (0.1, 1.0, and 2.0% w v^–1) by quantifying the number of cells in the biofilm and observing the biofilm structure after incubation for 24, 72, and 168 h. In addition, the biofilms were examined for their sensitivity to sodium hypochlorite. It was found that high concentrations of glucose reduced the number of viable cells in the biofilms and increased extracellular polymeric substance production. Moreover, biofilms formed at a glucose concentration of 1.0 or 2.0% were more resistant to sodium hypochlorite than those formed at a glucose concentration of 0.1%. This knowledge can be used to help design the most appropriate sanitation strategy.     

Protein quality control: the who’s who, the where’s and therapeutic escapes

In cells the quality of newly synthesized proteins is monitored in regard to proper folding and correct assembly in the early secretory pathway, the cytosol and the nucleoplasm. Proteins recognized as non-native in the ER will be removed and degraded by a process termed ERAD. ERAD of aberrant proteins is accompanied by various changes of cellular organelles and results in protein folding diseases. This review focuses on how the immunocytochemical labeling and electron microscopic analyses have helped to disclose the in situ subcellular distribution pattern of some of the key machinery proteins of the cellular protein quality control, the organelle changes due to the presence of misfolded proteins, and the efficiency of synthetic chaperones to rescue disease-causing trafficking defects of aberrant proteins.     

Levodopa Effects on Hand and Speech Movements in Patients with Parkinson’s Disease: A fMRI Study

Levodopa (L-dopa) effects on the cardinal and axial symptoms of Parkinson’s disease (PD) differ greatly, leading to therapeutic challenges for managing the disabilities in this patient’s population. In this context, we studied the cerebral networks associated with the production of a unilateral hand movement, speech production, and a task combining both tasks in 12 individuals with PD, both off and on levodopa (L-dopa). Unilateral hand movements in the off medication state elicited brain activations in motor regions (primary motor cortex, supplementary motor area, premotor cortex, cerebellum), as well as additional areas (anterior cingulate, putamen, associative parietal areas); following L-dopa administration, the brain activation profile was globally reduced, highlighting activations in the parietal and posterior cingulate cortices. For the speech production task, brain activation patterns were similar with and without medication, including the orofacial primary motor cortex (M1), the primary somatosensory cortex and the cerebellar hemispheres bilaterally, as well as the left- premotor, anterior cingulate and supramarginal cortices. For the combined task off L-dopa, the cerebral activation profile was restricted to the right cerebellum (hand movement), reflecting the difficulty in performing two movements simultaneously in PD. Under L-dopa, the brain activation profile of the combined task involved a larger pattern, including additional fronto-parietal activations, without reaching the sum of the areas activated during the simple hand and speech tasks separately. Our results question both the role of the basal ganglia system in speech production and the modulation of task-dependent cerebral networks by dopaminergic treatment.     

‘A Dispassionate and Objective Effort:’ Negotiating the First Study on the Biological Effects of Atomic Radiation

The National Academy of Science’s 1956 study on the Biological Effects of Atomic Radiation (BEAR) was designed to provide an objective analysis to assess conflicting statements by leading geneticists and by officials in the Atomic Energy Commission. Largely because of its status as a detached, non-governmental evaluation by eminent scientists, no studies have had a broader impact on the development of biological thinking in regard to nuclear policies. This paper demonstrates that despite the first BEAR study’s reputation as an objective and independent study, it was the product of careful negotiation between Academy scientists, the Atomic Energy Commission, and Britain’s Medical Research Council. This paper also reveals the fragility of the consensus that produced the Academy’s report, the range of political uses of the report, and the subsequent disaffection of the scientists who took part in it.     

Solution Structures of Casein Peptides: NMR, FTIR, CD, and Molecular Modeling Studies of αs1-Casein, 1–23

To determine its potential for interacting with other components of the casein micelle, the N-terminal section of bovine _s1-casein-B, residues 1-23, was investigated with nuclear magnetic resonance (NMR), Fourier transform infrared (FTIR) and circular dichroism (CD) spectroscopies, and molecular modeling. NMR data were not consistent with conventional -helical or -sheet structures, but changes in N-H proton chemical shifts suggested thermostable structures. Both CD and FTIR predicted a range of secondary structures for the peptide (30–40% turns, 25–30% extended) that were highly stable from 5°C to 25°C. Other conformational elements, such as loops and polyproline II helix, were indicated by FTIR only. Molecular dynamics simulation of the peptide predicted 32% turns and 27% extended, in agreement with FTIR and CD predictions and consistent with NMR data. This information is interpreted in accord with recent spectroscopic evidence regarding the nature of unordered conformations, leading to a possible role of _s1-casein (1–23) in facilitating casein-casein interactions.     

Alzheimer’s Disease and Epilepsy: A Perspective on the Opportunities for Overlapping Therapeutic Innovation

Early-onset Alzheimer’s disease (AD) is associated with variants in amyloid precursor protein (APP) and presenilin (PSEN) 1 and 2. It is increasingly recognized that patients with AD experience undiagnosed focal seizures. These AD patients with reported seizures may have worsened disease trajectory. Seizures in epilepsy can also lead to cognitive deficits, neuroinflammation, and neurodegeneration. Epilepsy is roughly three times more common in individuals aged 65 and older. Due to the numerous available antiseizure drugs (ASDs), treatment of seizures has been proposed to reduce the burden of AD. More work is needed to establish the functional impact of seizures in AD to determine whether ASDs could be a rational therapeutic strategy. The efficacy of ASDs in aged animals is not routinely studied, despite the fact that the elderly represents the fastest growing demographic with epilepsy. This leaves a particular gap in understanding the discrete pathophysiological overlap between hyperexcitability and aging, and AD more specifically. Most of our preclinical knowledge of hyperexcitability in AD has come from mouse models that overexpress APP. While these studies have been invaluable, other drivers underlie AD, e.g. PSEN2. A diversity of animal models should be more frequently integrated into the study of hyperexcitability in AD, which could be particularly beneficial to identify novel therapies. Specifically, AD-associated risk genes, in particular PSENs, altogether represent underexplored contributors to hyperexcitability. This review assesses the available studies of ASDs administration in clinical AD populations and preclinical studies with AD-associated models and offers a perspective on the opportunities for further therapeutic innovation.