Dear Editor,The importance of the medial entorhinal cortex(MEC)for memory and spatial navigation has been shown repeatedly in many species,including mice and humans[1,2].It is,therefore,not surprising that the connect...Dear Editor,The importance of the medial entorhinal cortex(MEC)for memory and spatial navigation has been shown repeatedly in many species,including mice and humans[1,2].It is,therefore,not surprising that the connectivity of this structure has been studied extensively over the past century,mainly using a range of anterograde and retrograde anatomical tracers[3].展开更多
Functional changes in synaptic transmission from the lateral entorhinal cortex to the dentate gyrus(LEC-DG)are considered responsible for the chronification of pain.However,the underlying alterations in fan cells,whic...Functional changes in synaptic transmission from the lateral entorhinal cortex to the dentate gyrus(LEC-DG)are considered responsible for the chronification of pain.However,the underlying alterations in fan cells,which are the predominant neurons in the LEC that project to the DG,remain elusive.Here,we investigated possible mechanisms using a rat model of complete Freund’s adjuvant(CFA)-induced inflammatory pain.We found a substantial increase in hyperpolarization-activated/cyclic nucleotide-gated currents(Ih),which led to the hyperexcitability of LEC fan cells of CFA slices.This phenomenon was attenuated in CFA slices by activating dopamine D2,but not D1,receptors.Chemogenetic activation of the ventral tegmental area-LEC projection had a D2 receptor-dependent analgesic effect.Intra-LEC microinjection of a D2 receptor agonist also suppressed CFA-induced behavioral hypersensitivity,and this effect was attenuated by pre-activation of the Ih.Our findings suggest that down-regulating the excitability of LEC fan cells through activation of the dopamine D2 receptor may be a strategy for treating chronic inflammatory pain.展开更多
Background：Recent clinical and preclinical studies have suggested that deep brain stimulation （DBS） can be used as a tool to enhance cognitive functions.The aim of the present study was to investigate the impact of...Background：Recent clinical and preclinical studies have suggested that deep brain stimulation （DBS） can be used as a tool to enhance cognitive functions.The aim of the present study was to investigate the impact of DBS at three separate targets in the Papez circuit,including the anterior nucleus of thalamus （ANT）,the entorhinal cortex （EC）,and the fornix （FX）,on cognitive behaviors in an Alzheimer＇s disease （AD） rat model.Methods：Forty-eight rats were subjected to an intrahippocampal injection ofamyloid peptides 1-42 to induce an AD model.Rats were divided into six groups：DBS and sham DBS groups of ANT,EC,and FX.Spatial learning and memory were assessed by the Morris water maze （MWM）.Recognition memory was investigated by the novel object recognition memory test （NORM）.Locomotor and anxiety-related behaviors were detected by the open field test （OF）.By using two-way analysis of variance （ANOVA）,behavior differences between the six groups were analyzed.Results：In the MWM,the ANT,EC,and FX DBS groups performed differently in terms of the time spent in the platform zone （F（2.23） =6.04,P ＜ 0.01）,the frequency of platform crossing （F（2,23） =11.53,P ＜ 0.001）,and the percent time spent within the platform quadrant （F（2,23） =6.29,P ＜ 0.01）.In the NORM,the EC and FX DBS groups spent more time with the novel object,although the ANT DBS group did not （F（2,23） =10.03,P ＜ 0.001）.In the OF,all of the groups showed a similar total distance moved （F（1.42） =1.14,P =0.29）and relative time spent in the center （F（2,42） =0.56,P =0.58）.Conclusions：Our results demonstrated that DBS of the EC and FX facilitated hippocampus-dependent spatial memory more prominently thanANT DBS.In addition,hippocampus-independent recognition memory was enhanced by EC and FX DBS.None of the targets showed side-effects of anxiety or locomotor behaviors.展开更多
Alzheimer's disease is the most common type of cognitive disorder,and there is an urgent need to develop more effective,targeted and safer therapies for patients with this condition.Deep brain stimulation is an in...Alzheimer's disease is the most common type of cognitive disorder,and there is an urgent need to develop more effective,targeted and safer therapies for patients with this condition.Deep brain stimulation is an invasive surgical treatment that modulates abnormal neural activity by implanting electrodes into specific brain areas followed by electrical stimulation.As an emerging therapeutic approach,deep brain stimulation shows significant promise as a potential new therapy for Alzheimer's disease.Here,we review the potential mechanisms and therapeutic effects of deep brain stimulation in the treatment of Alzheimer's disease based on existing clinical and basic research.In clinical studies,the most commonly targeted sites include the fornix,the nucleus basalis of Meynert,and the ventral capsule/ventral striatum.Basic research has found that the most frequently targeted areas include the fornix,nucleus basalis of Meynert,hippocampus,entorhinal cortex,and rostral intralaminar thalamic nucleus.All of these individual targets exhibit therapeutic potential for patients with Alzheimer's disease and associated mechanisms of action have been investigated.Deep brain stimulation may exert therapeutic effects on Alzheimer's disease through various mechanisms,including reducing the deposition of amyloid-β,activation of the cholinergic system,increasing the levels of neurotrophic factors,enhancing synaptic activity and plasticity,promoting neurogenesis,and improving glucose metabolism.Currently,clinical trials investigating deep brain stimulation for Alzheimer's disease remain insufficient.In the future,it is essential to focus on translating preclinical mechanisms into clinical trials.Furthermore,consecutive follow-up studies are needed to evaluate the long-term safety and efficacy of deep brain stimulation for Alzheimer's disease,including cognitive function,neuropsychiatric symptoms,quality of life and changes in Alzheimer's disease biomarkers.Researchers must also prioritize the initiation of multi-center clinical trials of deep brain stimulation with large sample sizes and target earlier therapeutic windows,such as the prodromal and even the preclinical stages of Alzheimer's disease.Adopting these approaches will permit the efficient exploration of more effective and safer deep brain stimulation therapies for patients with Alzheimer's disease.展开更多
The present study sought to explore the mechanism of action by which icariin, an active component of Epimedii Herba, treats Alzheimer＇s disease at the proteomics level. Two-dimensional gel electrophoresis was used to...The present study sought to explore the mechanism of action by which icariin, an active component of Epimedii Herba, treats Alzheimer＇s disease at the proteomics level. Two-dimensional gel electrophoresis was used to isolate total protein from the entorhinal cortex of senescence-accelerated mouse prone 8 （SAMP8） mice, and differential protein spots were obtained. Corresponding peptide mass fingerprinting was conducted through mass spectrography to identify differential protein spots. Twenty-six differential protein spots were found in the entorhinal area of SAMP8 mice at 8 weeks following intragastdc perfusion with icariin and double distilled water. Fourteen spots were identified, which were involved in mitochondrial energy metabolism, oxidative stress, and neuronal function. The results revealed that icafiin can regulate the expression of various proteins in the entorhinal cortex of SAMP8 mice, and treat Alzheimer＇s disease by improving mitochondfial function, suppressing oxidative stress, inhibiting neural cell apoptosis, and protecting neurons.展开更多
The rapidly increasing prevalence of cognitive impairment and Alzheimer＇s disease has the potential to create a major worldwide healthcare crisis. Structural MRI studies in patients with Alzheimer＇s disease and mild...The rapidly increasing prevalence of cognitive impairment and Alzheimer＇s disease has the potential to create a major worldwide healthcare crisis. Structural MRI studies in patients with Alzheimer＇s disease and mild cognitive impairment are currently attracting considerable interest. It is extremely important to study early structural and metabolic changes, such as those in the hippocampus, entorhinal cortex, and gray matter structures in the medial temporal lobe, to allow the early detection of mild cognitive impairment and AIzheimer＇s disease. The microstructural integrity of white matter can be studied with diffusion tensor imaging. Increased mean diffusivity and decreased fractional anisotropy are found in subjects with white matter damage. Functional imaging studies with positron emission tomography tracer compounds enable detection of amyloid plaques in the living brain in patients with Alzheimer＇s disease. In this review, we will focus on key findings from brain imaging studies in mild cognitive impairment and Alzheimer＇s disease, including structural brain changes studied with MRI and white matter changes seen with diffusion tensor imaging, and other specific imaging methodologies will also be discussed.展开更多
The medial entorhinal cortex of rodents is known to contain grid cells that exhibit precise periodic firing patterns based on the animal’s position,resulting in a distinct hexagonal pattern in space.These cells have ...The medial entorhinal cortex of rodents is known to contain grid cells that exhibit precise periodic firing patterns based on the animal’s position,resulting in a distinct hexagonal pattern in space.These cells have been extensively studied due to their potential to unveil the navigational computations that occur within the mammalian brain and interesting phenomena such as so-called grid cell distortions have been observed.Previous neuronal models of grid cells assumed their firing fields were independent of environmental boundaries.However,more recent research has revealed that the grid pattern is,in fact,dependent on the environment’s boundaries.When rodents are placed in nonsquare cages,the hexagonal pattern tends to become disrupted and adopts different shapes.We believe that these grid cell distortions can provide insights into the underlying neural circuitry involved in grid cell firing.To this end,a calibration circuit for grid cells is proposed.Our simulations demonstrate that this circuit is capable of reproducing grid distortions observed in several previous studies.Our model also reproduces distortions in place cells and incorporates experimentally observed distortions of speed cells,which present further opportunities for exploration.It generates several experimentally testable predictions,including an alternative behavioral description of boundary vector cells that predicts behaviors in nonsquare environments different from the current model of boundary vector cells.In summary,our study proposes a calibration circuit that reproduces observed grid distortions and generates experimentally testable predictions,aiming to provide insights into the neural mechanisms governing spatial computations in mammals.展开更多
Background:Previous studies have shown that expression levels of miR-181c are downregulated by amyloid-β(Aβ)deposition and chronic cerebral hypoperfusion,both factors largely associated with the development of AD.Mo...Background:Previous studies have shown that expression levels of miR-181c are downregulated by amyloid-β(Aβ)deposition and chronic cerebral hypoperfusion,both factors largely associated with the development of AD.Moreover,reduced 2-[18F]fluoro-2-deoxy-D-glucose(FDG)-PET brain metabolism and volume loss of regions of the medial temporal lobe have been generally recognized as hallmarks of AD.Based on this evidence,we have here investigated potential associations between serum levels of miR-181c-5p and these AD signatures in asymptomatic elderly subjects.Methods:Ninety-five normal elderly subjects underwent clinical,cognitive,structural MRI,and FDG-PET explorations.Serum expression levels of miR-181c-5p and plasma Aβ concentrations were further analyzed in this cohort.Regression analyses were performed to assess associations between serum miR-181c-5p levels and cognitive functioning,plasma Aβ,structural and metabolic brain changes.Results:Decreased serum expression of miR-181c-5p was associated with increased plasma levels of Aβ1–40,deficits in cortical glucose metabolism,and volume reduction of the entorhinal cortex.No significant associations were found between lower miR-181c-5p levels and cognitive deficits or cortical thinning.Conclusions:These findings suggest that deregulation of serum miR-181c-5p may indicate cerebral vulnerability in late life.展开更多
With the fast-growing aging population, dementia has become a health priority.However, in the past, medicine was largely dealing with physical disorders, and not enough knowledge and experience have been accumulated f...With the fast-growing aging population, dementia has become a health priority.However, in the past, medicine was largely dealing with physical disorders, and not enough knowledge and experience have been accumulated for mental health. The main and first symptom of this disorder is the loss of memory; hence, understanding the hippocampal formation is the key to tackling dementia. In 2007, a milestone book titled "Hippocampus Book" was published. One of the authors/editors is the 2014 Nobel Laureate in Physiology and Medicine, Professor John O'Keefe. It is a MUST-READ encyclopedia about the hippocampal formation, for those who wish to commit themselves to helping the patients with dementia. The formation consists of the hippocampus,entorhinal cortex, subiculum, presubiculum, parasubiculum, and dentate gyrus. The hippocampus is further divided into CA1, CA2, and CA3. The entorhinal cortex is the gateway of receiving all sensory information from the neocortex, while the subiculum is the exit for the efferent projections to the neocortex. Memory is divided into short-term and long-term memory. The former does not require protein synthesis while the latter does. The electrophysiological activities of creating these memories are short-term potentiation and long-term potentiation respectively. In most cases, the entorhinal cortex is the first structure to be damaged, and even short-term memory cannot be created. However, all except spatial memory are stored in the neocortex. Damage to the hippocampal formation would not affect the storage and retrieval of memories. Hence, past memories may remain intact in the early phases of the disorder. This devastating progressive disease has no cure. However, the highly plastic hippocampal formation may offer us some hope. It is the responsibility of the pharmaceutical industries to develop new drugs. Clinicians should add their efforts to the endeavor. The author would suggest that they explore insulin-like growth factors,brain stimulation, cell transplantation, and animal-assisted therapy to find some innovative solutions to help patients with dementia. As the current status of neuroscience stands, the animal-assisted therapy seems to stand out among all methods. It alleviates symptoms and stabilizes the ailment.展开更多
文摘Dear Editor,The importance of the medial entorhinal cortex(MEC)for memory and spatial navigation has been shown repeatedly in many species,including mice and humans[1,2].It is,therefore,not surprising that the connectivity of this structure has been studied extensively over the past century,mainly using a range of anterograde and retrograde anatomical tracers[3].
基金supported by the National Natural Science Foundation of China(81901119 and 81901142)Special Project on Innovation and Generation of Medical Support Capacity,and the Natural Science Foundation of Tibet(XZ2019ZRG-119),China.
文摘Functional changes in synaptic transmission from the lateral entorhinal cortex to the dentate gyrus(LEC-DG)are considered responsible for the chronification of pain.However,the underlying alterations in fan cells,which are the predominant neurons in the LEC that project to the DG,remain elusive.Here,we investigated possible mechanisms using a rat model of complete Freund’s adjuvant(CFA)-induced inflammatory pain.We found a substantial increase in hyperpolarization-activated/cyclic nucleotide-gated currents(Ih),which led to the hyperexcitability of LEC fan cells of CFA slices.This phenomenon was attenuated in CFA slices by activating dopamine D2,but not D1,receptors.Chemogenetic activation of the ventral tegmental area-LEC projection had a D2 receptor-dependent analgesic effect.Intra-LEC microinjection of a D2 receptor agonist also suppressed CFA-induced behavioral hypersensitivity,and this effect was attenuated by pre-activation of the Ih.Our findings suggest that down-regulating the excitability of LEC fan cells through activation of the dopamine D2 receptor may be a strategy for treating chronic inflammatory pain.
基金This study was supported by grants from the National Natural Science Foundation of China，the Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding，the Scientific Research Common Program of Beijing Municipal Commission of Education （No.KZ201510025029）.Conflict of Interest：None declared
文摘Background：Recent clinical and preclinical studies have suggested that deep brain stimulation （DBS） can be used as a tool to enhance cognitive functions.The aim of the present study was to investigate the impact of DBS at three separate targets in the Papez circuit,including the anterior nucleus of thalamus （ANT）,the entorhinal cortex （EC）,and the fornix （FX）,on cognitive behaviors in an Alzheimer＇s disease （AD） rat model.Methods：Forty-eight rats were subjected to an intrahippocampal injection ofamyloid peptides 1-42 to induce an AD model.Rats were divided into six groups：DBS and sham DBS groups of ANT,EC,and FX.Spatial learning and memory were assessed by the Morris water maze （MWM）.Recognition memory was investigated by the novel object recognition memory test （NORM）.Locomotor and anxiety-related behaviors were detected by the open field test （OF）.By using two-way analysis of variance （ANOVA）,behavior differences between the six groups were analyzed.Results：In the MWM,the ANT,EC,and FX DBS groups performed differently in terms of the time spent in the platform zone （F（2.23） =6.04,P ＜ 0.01）,the frequency of platform crossing （F（2,23） =11.53,P ＜ 0.001）,and the percent time spent within the platform quadrant （F（2,23） =6.29,P ＜ 0.01）.In the NORM,the EC and FX DBS groups spent more time with the novel object,although the ANT DBS group did not （F（2,23） =10.03,P ＜ 0.001）.In the OF,all of the groups showed a similar total distance moved （F（1.42） =1.14,P =0.29）and relative time spent in the center （F（2,42） =0.56,P =0.58）.Conclusions：Our results demonstrated that DBS of the EC and FX facilitated hippocampus-dependent spatial memory more prominently thanANT DBS.In addition,hippocampus-independent recognition memory was enhanced by EC and FX DBS.None of the targets showed side-effects of anxiety or locomotor behaviors.
基金supported by the Capital Fund for Health Improvement and Research,No.2022-2-2048(to WZ)the National Natural Science Foundation of China,No.81970992(to WZ)+3 种基金Capital Clinical Characteristic Application Research,No.Z121107001012161(to WZ)the Natural Science Foundation of Beijing,No.7082032(to WZ)the Key Technology R&D Program of Beijing Municipal Education Commission,No.KZ201610025030(to WZ)Project of Scientific and Technological Development of Traditional Chinese Medicine in Beijing,No.JJ2018-48(to WZ)。
文摘Alzheimer's disease is the most common type of cognitive disorder,and there is an urgent need to develop more effective,targeted and safer therapies for patients with this condition.Deep brain stimulation is an invasive surgical treatment that modulates abnormal neural activity by implanting electrodes into specific brain areas followed by electrical stimulation.As an emerging therapeutic approach,deep brain stimulation shows significant promise as a potential new therapy for Alzheimer's disease.Here,we review the potential mechanisms and therapeutic effects of deep brain stimulation in the treatment of Alzheimer's disease based on existing clinical and basic research.In clinical studies,the most commonly targeted sites include the fornix,the nucleus basalis of Meynert,and the ventral capsule/ventral striatum.Basic research has found that the most frequently targeted areas include the fornix,nucleus basalis of Meynert,hippocampus,entorhinal cortex,and rostral intralaminar thalamic nucleus.All of these individual targets exhibit therapeutic potential for patients with Alzheimer's disease and associated mechanisms of action have been investigated.Deep brain stimulation may exert therapeutic effects on Alzheimer's disease through various mechanisms,including reducing the deposition of amyloid-β,activation of the cholinergic system,increasing the levels of neurotrophic factors,enhancing synaptic activity and plasticity,promoting neurogenesis,and improving glucose metabolism.Currently,clinical trials investigating deep brain stimulation for Alzheimer's disease remain insufficient.In the future,it is essential to focus on translating preclinical mechanisms into clinical trials.Furthermore,consecutive follow-up studies are needed to evaluate the long-term safety and efficacy of deep brain stimulation for Alzheimer's disease,including cognitive function,neuropsychiatric symptoms,quality of life and changes in Alzheimer's disease biomarkers.Researchers must also prioritize the initiation of multi-center clinical trials of deep brain stimulation with large sample sizes and target earlier therapeutic windows,such as the prodromal and even the preclinical stages of Alzheimer's disease.Adopting these approaches will permit the efficient exploration of more effective and safer deep brain stimulation therapies for patients with Alzheimer's disease.
文摘The present study sought to explore the mechanism of action by which icariin, an active component of Epimedii Herba, treats Alzheimer＇s disease at the proteomics level. Two-dimensional gel electrophoresis was used to isolate total protein from the entorhinal cortex of senescence-accelerated mouse prone 8 （SAMP8） mice, and differential protein spots were obtained. Corresponding peptide mass fingerprinting was conducted through mass spectrography to identify differential protein spots. Twenty-six differential protein spots were found in the entorhinal area of SAMP8 mice at 8 weeks following intragastdc perfusion with icariin and double distilled water. Fourteen spots were identified, which were involved in mitochondrial energy metabolism, oxidative stress, and neuronal function. The results revealed that icafiin can regulate the expression of various proteins in the entorhinal cortex of SAMP8 mice, and treat Alzheimer＇s disease by improving mitochondfial function, suppressing oxidative stress, inhibiting neural cell apoptosis, and protecting neurons.
文摘The rapidly increasing prevalence of cognitive impairment and Alzheimer＇s disease has the potential to create a major worldwide healthcare crisis. Structural MRI studies in patients with Alzheimer＇s disease and mild cognitive impairment are currently attracting considerable interest. It is extremely important to study early structural and metabolic changes, such as those in the hippocampus, entorhinal cortex, and gray matter structures in the medial temporal lobe, to allow the early detection of mild cognitive impairment and AIzheimer＇s disease. The microstructural integrity of white matter can be studied with diffusion tensor imaging. Increased mean diffusivity and decreased fractional anisotropy are found in subjects with white matter damage. Functional imaging studies with positron emission tomography tracer compounds enable detection of amyloid plaques in the living brain in patients with Alzheimer＇s disease. In this review, we will focus on key findings from brain imaging studies in mild cognitive impairment and Alzheimer＇s disease, including structural brain changes studied with MRI and white matter changes seen with diffusion tensor imaging, and other specific imaging methodologies will also be discussed.
基金the European Union’s Horizon 2020 Framework Program for Research and Innovation under Specific Grant Agreement(SGA)Number 945539(Human Brain Project SGA3).
文摘The medial entorhinal cortex of rodents is known to contain grid cells that exhibit precise periodic firing patterns based on the animal’s position,resulting in a distinct hexagonal pattern in space.These cells have been extensively studied due to their potential to unveil the navigational computations that occur within the mammalian brain and interesting phenomena such as so-called grid cell distortions have been observed.Previous neuronal models of grid cells assumed their firing fields were independent of environmental boundaries.However,more recent research has revealed that the grid pattern is,in fact,dependent on the environment’s boundaries.When rodents are placed in nonsquare cages,the hexagonal pattern tends to become disrupted and adopts different shapes.We believe that these grid cell distortions can provide insights into the underlying neural circuitry involved in grid cell firing.To this end,a calibration circuit for grid cells is proposed.Our simulations demonstrate that this circuit is capable of reproducing grid distortions observed in several previous studies.Our model also reproduces distortions in place cells and incorporates experimentally observed distortions of speed cells,which present further opportunities for exploration.It generates several experimentally testable predictions,including an alternative behavioral description of boundary vector cells that predicts behaviors in nonsquare environments different from the current model of boundary vector cells.In summary,our study proposes a calibration circuit that reproduces observed grid distortions and generates experimentally testable predictions,aiming to provide insights into the neural mechanisms governing spatial computations in mammals.
基金This work was supported by research grants from the Spanish Ministry of Economy and Competitiveness(SAF2017-85310-R to JLC,PSI2017-85311-P to MA)the Regional Ministry of Innovation,Science and Enterprise,Junta de Andalucía(P12-CTS-2327 to JLC)+1 种基金the International Center on Aging CENIEPOCTEP(0348_CIE_6_E to MA)CIBERNED(CB06/05/1111 to JLC).
文摘Background:Previous studies have shown that expression levels of miR-181c are downregulated by amyloid-β(Aβ)deposition and chronic cerebral hypoperfusion,both factors largely associated with the development of AD.Moreover,reduced 2-[18F]fluoro-2-deoxy-D-glucose(FDG)-PET brain metabolism and volume loss of regions of the medial temporal lobe have been generally recognized as hallmarks of AD.Based on this evidence,we have here investigated potential associations between serum levels of miR-181c-5p and these AD signatures in asymptomatic elderly subjects.Methods:Ninety-five normal elderly subjects underwent clinical,cognitive,structural MRI,and FDG-PET explorations.Serum expression levels of miR-181c-5p and plasma Aβ concentrations were further analyzed in this cohort.Regression analyses were performed to assess associations between serum miR-181c-5p levels and cognitive functioning,plasma Aβ,structural and metabolic brain changes.Results:Decreased serum expression of miR-181c-5p was associated with increased plasma levels of Aβ1–40,deficits in cortical glucose metabolism,and volume reduction of the entorhinal cortex.No significant associations were found between lower miR-181c-5p levels and cognitive deficits or cortical thinning.Conclusions:These findings suggest that deregulation of serum miR-181c-5p may indicate cerebral vulnerability in late life.
文摘With the fast-growing aging population, dementia has become a health priority.However, in the past, medicine was largely dealing with physical disorders, and not enough knowledge and experience have been accumulated for mental health. The main and first symptom of this disorder is the loss of memory; hence, understanding the hippocampal formation is the key to tackling dementia. In 2007, a milestone book titled "Hippocampus Book" was published. One of the authors/editors is the 2014 Nobel Laureate in Physiology and Medicine, Professor John O'Keefe. It is a MUST-READ encyclopedia about the hippocampal formation, for those who wish to commit themselves to helping the patients with dementia. The formation consists of the hippocampus,entorhinal cortex, subiculum, presubiculum, parasubiculum, and dentate gyrus. The hippocampus is further divided into CA1, CA2, and CA3. The entorhinal cortex is the gateway of receiving all sensory information from the neocortex, while the subiculum is the exit for the efferent projections to the neocortex. Memory is divided into short-term and long-term memory. The former does not require protein synthesis while the latter does. The electrophysiological activities of creating these memories are short-term potentiation and long-term potentiation respectively. In most cases, the entorhinal cortex is the first structure to be damaged, and even short-term memory cannot be created. However, all except spatial memory are stored in the neocortex. Damage to the hippocampal formation would not affect the storage and retrieval of memories. Hence, past memories may remain intact in the early phases of the disorder. This devastating progressive disease has no cure. However, the highly plastic hippocampal formation may offer us some hope. It is the responsibility of the pharmaceutical industries to develop new drugs. Clinicians should add their efforts to the endeavor. The author would suggest that they explore insulin-like growth factors,brain stimulation, cell transplantation, and animal-assisted therapy to find some innovative solutions to help patients with dementia. As the current status of neuroscience stands, the animal-assisted therapy seems to stand out among all methods. It alleviates symptoms and stabilizes the ailment.
