Association Between Catheter Ablation and Dementia Among Patients With Atrial Fibrillation: A Systematic Review and Meta-analysis.

Atrial fibrillation (AF) is associated with an increased risk of Dementia. However, the association between catheter ablation (CA) in patients with atrial fibrillation and the risk of dementia is not well established, with conflicting results to date. We aimed to evaluate the association between CA patients and the risk of Dementia. We performed a systematic literature search using the PubMed, Embase, Scopus, and Cochrane libraries for relevant articles from inception until 10th May 2023. Hazard ratios (HR) were pooled using a random-effect model, and a P-value of < 0.05 was considered statistically significant. A total of 5 studies with 125,649 patients (30,192 in the CA group and 95,457 in the non-CA group) were included. The mean age of patients among CA and non-CA groups was comparable (58.7 vs 58.18). The most common comorbidity among CA and non-CA groups was hypertension (18.49% vs 81.51%), respectively. Pooled analysis of primary outcome showed that CA was associated with a significant reduction in the risk of Dementia (HR, 0.63 [95% CI: 0.52-0.77], P < 0.001). Similarly, pooled analysis of secondary outcomes showed that the patients with CA had a lower risk of Alzheimer's disease (HR, 0.78 [95% CI: 0.66-0.92], P < 0.001) compared with the non-CA group. However, there was no statistically significant difference in the risk of vascular dementia (HR, 0.63 [95% CI: 0.38-1.06], P = 0.08) between both groups of patients. Our study suggested that catheter ablation reduced the risk of dementia and Alzheimer's disease compared to the nonablation group of patients.

Association of Medicare Mandatory Bundled Payment Reform With Joint Replacement Surgery Use for Beneficiaries With Alzheimer Disease and Related Dementias.

Importance: Medicare beneficiaries with Alzheimer disease and related dementias (ADRD) are a particularly vulnerable group in whom arthritis is a frequently occurring comorbidity. Medicare's mandatory bundled payment reform-the Comprehensive Care for Joint Replacement (CJR) model-was intended to improve quality and reduce spending in beneficiaries undergoing joint replacement surgical procedures for arthritis. In the absence of adjustment for clinical risk, hospitals may avoid performing elective joint replacements for beneficiaries with ADRD. Objective: To evaluate the association of the CJR model with utilization of joint replacements for Medicare beneficiaries with ADRD. Design Setting and Participants: This cohort study used national Medicare data from 2013 to 2017 and multivariable linear probability models and a triple differences estimation approach. Medicare beneficiaries with a diagnosis of arthritis were identified from 67 metropolitan statistical areas (MSAs) mandated to participate in CJR and 104 control MSAs. Data were analyzed from July 2020 to July 2021. Exposures: Implementation of the CJR model in 2016. Main Outcomes and Measures: Outcomes were separate binary indicators for whether or not a beneficiary underwent hip or knee replacement. Key independent variables were the MSA group, before-CJR and after-CJR phase, ADRD diagnosis, and their interactions. The linear probability models controlled for beneficiary characteristics, MSA fixed effects, and time trends. Results: The study included 24 598 729 beneficiary-year observations for 9 624 461 unique beneficiaries, of which 250 168 beneficiaries underwent hip and 474 751 underwent knee replacements. The mean (SD) age of the 2013 cohort was 77.1 (7.9) years, 3 110 922 (66.4%) were women, 3 928 432 (83.8%) were non-Hispanic White, 792 707 (16.9%) were dually eligible for Medicaid, and 885 432 (18.9%) had an ADRD diagnosis. Before CJR implementation, joint replacement rates were lower among beneficiaries with ADRD (hip replacements: 0.38% vs 1.17% for beneficiaries with and without ADRD, respectively; P < .001; knee replacements: 0.70% vs 2.25%; P < .001). After controlling for relevant covariates, CJR was associated with a 0.07-percentage-point decline in hip replacements for beneficiaries with ADRD (95% CI, -0.13 to -0.001; P = .046) and a 0.07-percentage-point decline for beneficiaries without ADRD (95% CI, -0.12 to -0.02; P = .01) residing in CJR MSAs compared with beneficiaries in control MSAs. However, this change in hip replacement rates for beneficiaries with ADRD was not statistically significantly different from the change for beneficiaries without ADRD (percentage point difference: 0.01; 95% CI, -0.08 to 0.09; P = .88). No statistically significant changes in knee replacement rates were noted for beneficiaries with ADRD compared with those without ADRD with CJR implementation (percentage point difference: -0.03, 95% CI, -0.09 to 0.02; P = .27). Conclusions and Relevance: In this cohort study of Medicare beneficiaries with arthritis, the CJR model was not associated with a decline in joint replacement utilization among beneficiaries with ADRD compared with beneficiaries without ADRD in the first 2 years of the program, thereby alleviating patient selection concerns.

Stem Cells: Innovative Therapeutic Options for Neurodegenerative Diseases?

Neurodegenerative diseases are characterized by the progressive loss of structure and/or function of both neurons and glial cells, leading to different degrees of pathology and loss of cognition. The hypothesis of circuit reconstruction in the damaged brain via direct cell replacement has been pursued extensively so far. In this context, stem cells represent a useful option since they provide tissue restoration through the substitution of damaged neuronal cells with exogenous stem cells and create a neuro-protective environment through the release of bioactive molecules for healthy neurons, as well. These peculiar properties of stem cells are opening to potential therapeutic strategies for the treatment of severe neurodegenerative disorders, for which the absence of effective treatment options leads to an increasingly socio-economic burden. Currently, the introduction of new technologies in the field of stem cells and the implementation of alternative cell tissues sources are pointing to exciting frontiers in this area of research. Here, we provide an update of the current knowledge about source and administration routes of stem cells, and review light and shadows of cells replacement therapy for the treatment of the three main neurodegenerative disorders (Amyotrophic lateral sclerosis, Parkinson's, and Alzheimer's disease).

Transplantation of GABAergic Interneuron Progenitor Attenuates Cognitive Deficits of Alzheimer's Disease Model Mice.

Excitatory (E) and inhibitory (I) balance of neural network activity is essential for normal brain function and of particular importance to memory. Disturbance of E/I balance contributes to various neurological disorders. The appearance of neural hyperexcitability in Alzheimer's disease (AD) is even suggested as one of predictors of accelerated cognitive decline. In this study, we found that GAD67+, Parvalbumin+, Calretinin+, and Neuropeptide Y+ interneurons were progressively lost in the brain of APP/PS1 mice. Transplanted embryonic medial ganglionic eminence derived interneuron progenitors (IPs) survived, migrated, and differentiated into GABAergic interneuron subtypes successfully at 2 months after transplantation. Transplantation of IPs hippocampally rescued impaired synaptic plasticity and cognitive deficits of APP/PS1 transgenic mice, concomitant with a suppression of neural hyperexcitability, whereas transplantation of IPs failed to attenuate amyloid-ß accumulation, neuroinflammation, and synaptic loss of APP/PS1 transgenic mice. These observations indicate that transplantation of IPs improves learning and memory of APP/PS1 transgenic mice via suppressing neural hyperexcitability. This study highlights a causal contribution of GABAergic dysfunction to AD pathogenesis and the potentiality of IP transplantation in AD therapy.

Background Risk Factors Associated with Shunt Intervention for Possible Idiopathic Normal Pressure Hydrocephalus: A Nationwide Hospital-Based Survey in Japan.

BACKGROUND: Patients with idiopathic normal-pressure hydrocephalus (iNPH) are typically older adults with multiple comorbidities that are associated with a reduction in the efficacy of iNPH treatment via cerebrospinal fluid (CSF) shunt placement. OBJECTIVE: The present study aimed to investigate the effectiveness of CSF shunt for iNPH using data from a nationwide epidemiological survey in Japan. METHODS: We examined 1,423 patients (581 women) aged ≥60 years (median age [25%-75%]: 77 [73-80] years) who were diagnosed with iNPH following a hospital visit in 2012. Patients who experienced an improvement of at least one modified Rankin Scale (mRS) grade after the CSF shunt were classified as "improvement" while the remaining patients were classified as "non-improvement." The efficacy of the shunt intervention (n = 842) was analyzed using a binomial logistic regression analysis. RESULTS: An analysis of risk factors associated with shunt placement in patients with mRS grade 2 revealed an association between comorbid chronic ischemic lesions (odds ratio [OR], 2.28; 95% confidence interval [CI], 1.11-4.67; p = 0.025) and cervical spondylosis (OR, 3.62; 95% CI, 1.15-11.34; p = 0.027). Patients with mRS grade 3 at study entry had an association with comorbid Alzheimer's disease (OR, 3.02; 95% CI, 1.44-6.31; p = 0.003). CONCLUSIONS: The results presented here showed that any age-related risk is minimal and should not be cause for rejection of surgical treatment options. Clinical decisions regarding CSF shunt should be individualized to each patient, with adequate consideration of the relative risks and benefits, including maximizing a healthy life expectancy.

Neuro-restorative effect of sertoli cell transplants in a rat model of amyloid beta toxicity.

Alzheimer's disease (AD) is a degenerative nerve disease which adversely affects memory and learning skills. Currently, there is no disease-modifying therapeutic approach for AD. However, a growing body of literature suggests cell based therapies as a promising remedy for neurological disorders. Among the potential cell sources, testis- derived Sertoli cells (SCs) appear to be an attractive choice due to their immune-privileged capacities. Herein, we investigated the neuro-restorative/protective effects of SC transplants in a rat model of amyloid beta toxicity. To this end, GATA-4 and vimentin positive SCs were transplanted into rats with amyloid beta induced hippocampal lesions. According to our in vivo results, implanted SCs survived, exhibited reduction in both apoptosis as well as astrocytic migration. Additionally, transplantation of SCs restored hippocampus dependent memory and learning, along with the recovery of long-term synaptic plasticity. Taken together, these data indicate that SCs are a valuable source for cell-based therapies particularly aimed at AD.

CD11a expression distinguishes infiltrating myeloid cells from plaque-associated microglia in Alzheimer's disease.

Alzheimer's disease (AD) is the leading cause of age-related neurodegeneration and is characterized neuropathologically by the accumulation of insoluble beta-amyloid (Aß) peptides. In AD brains, plaque-associated myeloid (PAM) cells cluster around Aß plaques but fail to effectively clear Aß by phagocytosis. PAM cells were originally thought to be brain-resident microglia. However, several studies have also suggested that Aß-induced inflammation causes peripheral monocytes to enter the otherwise immune-privileged brain. The relationship between AD progression and inflammation in the brain remains ambiguous because microglia and monocyte-derived macrophages are extremely difficult to distinguish from one another in an inflamed brain. Whether PAM cells are microglia, peripheral macrophages, or a mixture of both remains unclear. CD11a is a component of the ß2 integrin LFA1. We have determined that CD11a is highly expressed on peripheral immune cells, including macrophages, but is not expressed by mouse microglia. These expression patterns remain consistent in LPS-treated inflamed mice, as well as in two mouse models of AD. Thus, CD11a can be used as a marker to distinguish murine microglia from infiltrating peripheral immune cells. Using CD11a, we show that PAM cells in AD transgenic brains are comprised entirely of microglia. We also demonstrate a novel fluorescence-assisted quantification technique (FAQT), which reveals a significant increase in T lymphocytes, especially in the brains of female AD mice. Our findings support the notion that microglia are the lead myeloid players in AD and that rejuvenating their phagocytic potential may be an important therapeutic strategy.

A Mesenchymal Stem Cell Line Transplantation Improves Neurological Function and Angiogenesis in Intraventricular Amyloid ß-Infused Rats.

BACKGROUND: Mesenchymal stem cell transplantation is demonstrated to improve neurological performance in neurodegenerative diseases including Alzheimer's disease. OBJECTIVE: The objective of this study is to understand the underlying mechanism of such improvement. METHODS: Amyloid ß (Aß) peptide was infused into the lateral ventricle of adult Wister rats using the osmotic pump. After 15 days of continuous infusion, a mesenchymal stem cell line (B10) was transplanted in the lateral ventricle. Learning-related behavior was evaluated by 2-way shuttle avoidance test. Fifteen days after B10 transplantation, pathological and expressional changes were evaluated. RESULTS: Compared to sham group, learning-related behavior was significantly decreased in Aß-infused non-transplanted group, but not in B10-transplanted group. Nissl staining results demonstrated that the number of hippocampal pyramidal neurons in CA1 area in B10-transplanted group was similar to the sham group, whereas that was decreased in Aß-infused non-transplanted group. Aß mainly deposited in the vessels of the brains of Aß-infused non-transplanted rats, which was decreased by B10 transplantation. Moreover, B10 transplantation increased vessel density as well as endoglin positive cells. The number of astrocyte and microglia was decreased in Aß-infused non-transplanted group, which was returned to the level of sham animals by B10 transplantation. Real-time PCR and immunostaining results showed that B10 transplantation significantly increased IL-1ß mRNA and protein expression. CONCLUSION: Thus, our result showed that MSC transplantation effectively decreased Aß deposition in the cerebral vessel and increased angiogenesis, which could be a possible cause of improved neurological performance in Aß-infused AD model rats.

Anesthetic Isoflurane or Desflurane Plus Surgery Differently Affects Cognitive Function in Alzheimer's Disease Transgenic Mice.

Anesthesia/surgery could be associated with cognitive impairment and Alzheimer's disease neuropathogenesis. However, whether surgery under different anesthetics has different effects on cognitive function remains largely unknown. We therefore set out to compare effects of anesthetic isoflurane or desflurane plus surgery on cognitive function and hippocampus levels of synaptic marker (postsynaptic density-95 and synaptophysin) and ATP. Five-month-old AD Transgenic (Tg) (FAD5X) and wild-type male mice received isoflurane or desflurane plus abdominal surgery. We assessed cognitive function in Barnes maze and measured hippocampus levels of postsynaptic density-95, synaptophysin, and ATP in the mice. We determined whether vitamin K2 could mitigate these anesthesia/surgery-induced changes. Isoflurane, but not desflurane, plus surgery increased escape latency and escape distance in Barnes maze probe test and reduced postsynaptic density-95, synaptophysin, and ATP levels as compared to control condition in AD Tg mice. Vitamin K2 attenuated the anesthesia/surgery-induced changes in the AD Tg mice. These findings suggest that isoflurane, but not desflurane, plus surgery might induce cognitive impairment via causing brain energy deficits. Pending confirmative studies in both animals and humans suggest desflurane could be a better choice for AD patients when surgery is needed. Moreover, vitamin K2 could treat cognitive deficiency associated with anesthesia and surgery.

Effects of surgery and propofol-remifentanil total intravenous anesthesia on cerebrospinal fluid biomarkers of inflammation, Alzheimer's disease, and neuronal injury in humans: a cohort study.

BACKGROUND: Surgery and anesthesia have been linked to postoperative cognitive disturbance and increased risk of Alzheimer's disease. It is not clear by which mechanisms this increased risk for cognitive disease is mediated. Further, amyloid ß production has been suggested to depend on the sleep-wake cycle and neuronal activity. The aim of the present study was to examine if cerebrospinal fluid (CSF) concentrations of a number of biomarkers for Alzheimer's disease-related processes, including amyloid ß, neuronal injury, and inflammation, changed over time during intravenous anesthesia in surgical patients. METHODS: We included patients scheduled for hysterectomy via laparotomy during general anesthesia with intravenous propofol and remifentanil. CSF samples were obtained before, during, and after surgery (5 h after induction) and tested for 27 biomarkers. Changes over time were tested with linear mixed effects models. RESULTS: A total of 22 patients, all females, were included. The mean age was 50 years (± 9 SD). The mean duration of the anesthesia was 145 min (± 40 SD). Interleukin (IL)-6, IL-8, monocyte chemoattractant protein 1, and vascular endothelial growth factor A increased over time. IL-15 and IL-7 decreased slightly over time. Macrophage inflammatory protein 1ß and placental growth factor also changed significantly. There were no significant effects on amyloid ß (Aß) or tau biomarkers. CONCLUSIONS: Surgery and general anesthesia with intravenous propofol and remifentanil induce, during and in the short term after the procedure, a neuroinflammatory response which is dominated by monocyte attractants, without biomarker signs of the effects on Alzheimer's disease pathology or neuronal injury.

[Cataract surgery among 50 Alzheimer's patient (55 eyes)]. / Chirurgie de la cataracte chez 50 patients Alzheimer (55 yeux).

OBJECTIVE: Cataract surgery for 50 Alzheimer patients (55 eyes). METHODS: Cinquante Alzheimer's patients with 0≤MMS≤25, with bilateral disabling cataracts were included for surgery. The surgical technique is analyzed. RESULTS AND CONCLUSION: The preoperative examination of Alzheimer's patients is time consuming and requires experience in this area, which is important to integrate into the practice of ophthalmology. The type of cataract is unusual, with a predilection for pseudoexfoliation syndrome and zonular fragility that has to be managed during surgery. The procedure may be performed under local anesthesia. Three months after surgery, Alzheimer's patients demonstrated improved visual acuity (P<0.001) with no worsening of their dementia.

[Impact of sagittal balance parameters on life quality in elderly and senile patients after surgery for degenerative lumbar spine stenosis]. / Vliianie parametrov sagittal'nogo balansa na kachestvo zhizni u patsientov pozhilogo i starcheskogo vozrasta, operirovannykh po povodu degenerativnogo stenoza poiasnichnogo otdela pozvonochnika.

INTRODUCTION: As the life span and proportion of people over 65 years increase, the incidence of degenerative lumbar spine stenosis grows proportionally. Various parameters of the spinopelvic relationships are used to predict surgical treatment outcomes in patients with degenerative spine diseases. There are no unified protocols for evaluation, in terms of the sagittal balance, of surgical treatment outcomes in elderly patients. PURPOSE: To study the impact of sagittal balance parameters on the life quality of elderly and senile patients after surgery for degenerative stenosis of the lumbar spine. MATERIAL AND METHODS: The study included 109 patients. Decompression was performed in the first group of 53 patients. Decompression and stabilization were performed in the second group of 27 patients. In the third group of 29 patients, XLIF indirect decompression, scoliosis correction, reconstruction of disturbed spinopelvic relationships, and stabilization were carried out. We evaluated the following sagittal balance parameters: pelvic incidence (PI), sacral slope (SS), pelvic tilt (PT), lumbar lordosis (LL), and PI minus LL (PI-LL). The quality of life indicators were assessed using VAS, ODI, and SF36 scores. RESULTS: In the first group, there were not statistically significant differences for PT≤20° and PT>20°. A statistically significant change in the PI-LL parameter (p=0.0263) was in the first group. A decrease in PI-LL was accompanied by regression of pain (p<10-4). In the second group, comparison of the quality of life indicators revealed no statistically significant differences between PT≤20° and PT>20° as well as PI-LL≤10° and PI-LL>10 in the postoperative period. In the third group, postoperative improvement in PT (p=0.0002) and PI-LL (p=0.0008) parameters was accompanied by a decrease in pain in the legs (p=0.0002) and lumbar spine (p=0.0001). CONCLUSION: Improvement in the quality of life indicators in 48.6% of cases was achieved by decompression only; the sagittal balance parameters had no significant impact on quality of life. In 24.8% of cases, improvement in the quality of life indicators was achieved by decompression and stabilization because the dominant clinical neurological syndrome was instability. Reduced quality of life in 26.6% of patients was caused by disturbed spinopelvic relationships. Application of the XLIF technique in these patients provides statistically significant restoration of the sagittal balance parameters, PT and PI-LL, which improves quality of life.

[Neuropsychological benefit of cataract surgery among sight impaired Alzheimer's patient]. / Modifications des troubles du comportement après l'opération de la cataracte chez les patients Alzheimer.

PURPOSE: Evaluation of neuropsychological benefits of cataract surgery for 46 Alzheimer patients on the basis of neuropsychiatric index (NPI), as the principal criterion of analysis of the VIVA study. METHODS: Prospective, monocentric neuropsychiatric study, performed from 2005 to 2011. All Alzheimer's patients with 10

Immunotherapeutic effects of lymphocytes co-cultured with human cord blood-derived multipotent stem cells transplantation on APP/PS1 mice.

Alzheimer's disease (AD) is an inexorable neurodegenerative disease that involves neuroinflammation in the brain, in addition to abnormal accumulation of amyloid-ß (Aß) and hyperphosphorylated tau. Evidence shows that human cord blood-derived multipotent stem cells (CB-SCs) can modulate autoimmune responses by altering regulatory T cells (Tregs). Our previous study found that CB-SCs could regulate the peripheral immune system of AD patients in vitro, mainly increasing the proportion of Tregs and anti-inflammatory cytokines. To further investigate the effects of lymphocytes co-cultured with CB-SCs on AD, the APP/PS1 mice received monthly transplants of lymphocytes co-cultured with CB-SCs for 4 months. Then, the ethological and biochemical experiments were conducted. We found that APP/PS1 mice injected with lymphocytes co-cultured with CB-SCs showed improved spatial learning, which significantly correlated with fewer Aß plaques in brain. The present study also indicated that lymphocytes co-cultured with CB-SCs could promote the protective and reparative cytokines in the peripheral blood and brain to alleviate neuroinflammation in AD mice. These findings conclude that the systemic transplantation of lymphocytes co-cultured with CB-SCs can improve cognitive and pathological impairment of APP/PS1 mice via an immunomodulatory effect.

Moving from the Dish to the Clinical Practice: A Decade of Lessons and Perspectives from the Pre-Clinical and Clinical Stem Cell Studies for Alzheimer's Disease.

To date, there is no definitive treatment for Alzheimer's disease (AD). The realm of stem cells is very promising in regenerative medicine, particularly neurodegenerative disorders. Various types of stem cells have been used in multiple trials on AD models, trying to find an innovative management of this disease. In this systematic review, we trace the published preclinical and clinical data throughout the last decade, to show how much knowledge we gained so far in this field and the future perspectives of stem cells in AD treatment.

Neurorestorative Role of Stem Cells in Alzheimer's Disease: Astrocyte Involvement.

Neurogenesis is maintained in both neonatal and adult brain, although it is dramatically reduced in aged neurogenic brain region such as the subgranular layer and subventricular zone of the dentate gyrus (DG). Astrocytes play important roles for survival and maintenance of neurons as well as maintenance of neurogenic niche in quiescent state. Aß can induce astrocyte activation which give rise to produce reactive oxygen species (ROS) and cytotoxic cytokines and chemokines, and subsequently induce neuronal death. Unfortunately, the current therapeutic medicines have been limited to reduce the symptoms and delay the pathogenesis of Alzheimer's disease (AD), but not to cure it. Stem cells enhance neurogenesis and Aß clearing as well as improved cognitive impairment. Neurotrophins and growth factors which are produced from both stem cells and astrocytes also have neuroprotective effects via neurogenesis. Secreted factors from both astrocytes and neural stem cells also are influenced in neurogenesis and neuron survival in neurodegenerative diseases. Transplanted stem cells overexpressing neurogenic factors may be an effective and therapeutic tool to enhance neurogenesis for AD.

Deep Assessment: A Novel Framework for Improving the Care of People with Very Advanced Alzheimer's Disease.

Best practice in understanding and caring for people with advanced Alzheimer's disease presents extraordinary challenges. Their severe and deteriorating cognitive impairments are such that carers find progressive difficulty in authentically ascertaining and responding to interests, preferences, and needs. Deep assessment, a novel multifaceted framework drawn from research into the experiences of others with severe cognitive impairments, has potential to empower carers and other support professionals to develop an enhanced understanding of people with advanced Alzheimer's disease and so deliver better calibrated care in attempts to maximize quality of life. Deep assessment uses a combination of techniques, namely, Behaviour State Observation, Triangulated Proxy Reporting, and Startle Reflex Modulation Measurement, to deliver a comprehensive and deep assessment of the inner states (awareness, preferences, likes, and dislikes) of people who cannot reliably self-report. This paper explains deep assessment and its current applications. It then suggests how it can be applied to people with advanced Alzheimer's disease to develop others' understanding of their inner states and to help improve their quality of life. An illustrative hypothetical vignette is used to amplify this framework. We discuss the potential utility and efficacy of this technique for this population and we also propose other human conditions that may benefit from research using a deep assessment approach.

Enhanced Hippocampal Neurogenesis in APP/Ps1 Mouse Model of Alzheimer's Disease After Implantation of VEGF-loaded PLGA Nanospheres.

During adult life, hippocampus is an important brain region involved in neurogenesis. The generation and cell death of newly generated neuronal cells in this region have critical roles in brain maintenance and alterations in these processes are seen in Alzheimer's disease (AD). For the purpose of carrying out a neuroregenerative strategy, we propose a novel approach based on the encapsulation of vascular endothelial growth factor (VEGF) in poly (lactic co-glycolic acid) (PLGA) biodegradable nanospheres (NS) administered by craniotomy to stimulate the proliferation of neuronal precursors in a transgenic mouse model of AD. VEGF loaded nanospheres were prepared by double emulsion solvent evaporation technique, obtaining 200 nm nanospheres with a biphasic release profile. After demonstrating their efficacy in the proliferation and differentiation of neuronal cell cultures, in vivo studies were carried out. 3 months after VEGF-NS were implanted directly into the cerebral cortex of APP/Ps1 mice, the determination of BrdU(+) cells in the whole hippocampal region and specifically in the dentate gyrus, demonstrated a significantly enhanced cellular proliferation in VEGF-NS treated group. These results were also confirmed showing an increased number of DCX(+) and NeuN(+) cells. Hence, PLGA-VEGF nanospheres may be a potential strategy to modulate proliferative neuronal progenitors in the hippocampal region, and therefore, provide new insight for future therapeutic approaches in AD.