Remnant Copper Cation-Assisted Atom Mixing in Multicomponent Nanoparticles.

Nanostructured high-/medium-entropy compounds have emerged as important catalytic materials for energy conversion technologies, but complex thermodynamic relationships involved with the element mixing enthalpy have been a considerable roadblock to the formation of stable single-phase structures. Cation exchange reactions (CERs), in particular with copper sulfide templates, have been extensively investigated for the synthesis of multicomponent heteronanoparticles with unconventional structural features. Because copper cations within the host copper sulfide templates are stoichiometrically released with incoming foreign cations in CERs to maintain the overall charge balance, the complete absence of Cu cations in the nanocrystals after initial CERs would mean that further compositional variation would not be possible by subsequent CERs. Herin, we successfully retained a portion of Cu cations within the silver sulfide (Ag2S) and gold sulfide (Au2S) phases of Janus Cu2-xS-M2S (M = Ag, Au) nanocrystals after the CERs, by partially suppressing the transformation of the anion sublattice that inevitably occurs during the introduction of external cations. Interestingly, the subsequent CERs on Janus Cu1.81S-M2S (M = Ag, Au), by utilizing the remnant Cu cations, allowed the construction of Janus Cu1.81S-AgxAuyS, which preserved the initial heterointerface. The synthetic strategy described in this work to suppress the complete removal of the Cu cation from the template could fabricate the CER-driven heterostructures with greatly diversified compositions, which exhibit unusual optical and catalytic properties.

Regional Cerebral Blood Flow Correlates of Neuropsychiatric Symptom Domains in Early Alzheimer's Disease.

Although various neuropsychiatric symptoms are frequently accompanied with Alzheimer's disease (AD) and pose a substantial burden to both patients and caregivers, their neurobiological underpinnings remain unclear. This study investigated associations between regional cerebral blood flow (rCBF) and neuropsychiatric symptom domains in early AD. A total of 59 patients with early AD underwent brain technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) single-photon emission computed tomography (SPECT) scans. Neuropsychiatric symptoms were assessed by the Neuropsychiatric Inventory and clustered into the affective, apathy, hyperactivity, and psychotic domains. A voxel-wise multiple regression analysis was performed with four domain scores as independent variables and age, sex, and Mini-Mental State Examination scores as covariates. The affective domain score was negatively correlated with rCBF in the prefrontal cortex, thalamus, and caudate. The apathy domain score showed inverse correlations with rCBF in the prefrontal and pre/postcentral gyri and midbrain. Patients with higher hyperactivity domain scores had increased rCBF in the prefrontal and temporal lobes. The psychotic symptom domain was positively correlated with rCBF in the cuneus and negatively associated with rCBF in the prefrontal, cingulate, and occipital regions and putamen. The score of each neuropsychiatric symptom domain showed the differential correlates of brain perfusion, while altered rCBF in the prefrontal cortex was found in all domains. Although preliminary, our results may suggest common and distinct patterns of rCBF underlying neuropsychiatric symptoms in early AD. Further studies with larger samples and control participants are warranted to confirm these findings.

Short-Term Efficacy of Transcranial Focused Ultrasound to the Hippocampus in Alzheimer's Disease: A Preliminary Study.

Preclinical studies have suggested that low-intensity transcranial focused ultrasound (tFUS) may have therapeutic potential for Alzheimer's disease (AD) by opening the blood-brain barrier (BBB), reducing amyloid pathology, and improving cognition. This study investigated the effects of tFUS on BBB opening, regional cerebral metabolic rate of glucose (rCMRglu), and cognitive function in AD patients. Eight patients with AD received image-guided tFUS to the right hippocampus immediately after intravenous injection of microbubble ultrasound contrast agents. Patients completed magnetic resonance imaging (MRI), 18F-fluoro-2-deoxyglucose positron emission tomography (PET), and cognitive assessments before and after the sonication. No evidence of transient BBB opening was found on T1 dynamic contrast-enhanced MRI. However, immediate recall (p = 0.03) and recognition memory (p = 0.02) were significantly improved on the verbal learning test. PET image analysis demonstrated increased rCMRglu in the right hippocampus (p = 0.001). In addition, increases of hippocampal rCMRglu were correlated with improvement in recognition memory (Spearman's ρ = 0.77, p = 0.02). No adverse event was observed. Our results suggest that tFUS to the hippocampus of AD patients may improve rCMRglu of the target area and memory in the short term, even without BBB opening. Further larger sham-controlled trials with loger follow-up are warranted to evaluate the efficacy and safety of tFUS in patients with AD.

A pilot clinical study of low-intensity transcranial focused ultrasound in Alzheimer's disease.

PURPOSE: Increasing attention has been paid to low-intensity transcranial focused ultrasound (tFUS) for its potential therapeutic effects in Alzheimer's disease (AD). While preclinical studies have shown promising therapeutic effects of low-intensity tFUS in AD models, its efficacy and safety remain unclear in humans. In this pilot study, we investigated the effects of low-intensity tFUS on blood-brain barrier opening, the regional cerebral metabolic rate of glucose (rCMRglu), and cognition in patients with AD. METHODS: After receiving institutional review board approval, four patients with AD received tFUS to the hippocampus immediately after an intravenous injection of a microbubble ultrasound contrast agent. Sonication was delivered at low-intensity, at a pressure level below the threshold for blood-brain barrier opening. Patients underwent brain magnetic resonance imaging, 18F-fluoro-2-deoxyglucose positron emission tomography, and neuropsychological assessments before and after the tFUS procedure. A whole-brain voxel-wise paired t test was conducted to compare rCMRglu before and after tFUS. RESULTS: The sonication, as anticipated, did not show evidence of active blood-brain barrier opening on T1 dynamic contrast-enhanced magnetic resonance imaging. rCMRglu in the superior frontal gyrus (P<0.001), middle cingulate gyrus (P<0.001), and fusiform gyrus increased after tFUS (P=0.001). Patients demonstrated mild improvement in measures of memory, executive, and global cognitive function following tFUS. No adverse events were reported. CONCLUSION: These results suggest that hippocampal sonication with low-intensity tFUS may have beneficial effects on cerebral glucose metabolism and cognitive function in patients with AD. Further larger studies are needed to confirm the therapeutic efficacy of tFUS in AD.

The Impact of Amyloid-Beta Positivity with 18F-Florbetaben PET on Neuropsychological Aspects in Parkinson's Disease Dementia.

The neuropathology of Parkinson's disease dementia (PDD) is heterogenous, and the impacts of each pathophysiology and their synergistic effects are not fully understood. The aim of this study was to evaluate the frequency and impacts of co-existence with Alzheimer's disease in patients with PDD by using 18F-florbetaben PET imaging. A total of 23 patients with PDD participated in the study. All participants underwent 18F-florbetaben PET and completed a standardized neuropsychological battery and assessment of motor symptoms. The results of cognitive tests, neuropsychiatric symptoms, and motor symptoms were analyzed between the positive and negative 18F-florbetaben PET groups. Four patients (17.4%) showed significant amyloid burden. Patients with amyloid-beta showed poorer performance in executive function and more severe neuropsychiatric symptoms than those without amyloid-beta. Motor symptoms assessed by UPDRS part III and the modified H&Y Scale were not different between the two groups. The amyloid PET scan of a patient with PDD can effectively reflect a co-existing Alzheimer's disease pathology. Amyloid PET scans might be able to help physicians of PDD patients showing rapid progression or severe cognitive/behavioral features.

Janus to Core-Shell to Janus: Facile Cation Movement in Cu2-xS/Ag2S Hexagonal Nanoplates Induced by Surface Strain Control.

Nanocrystals with multiple compositions and heterointerfaces have received great attention due to promising multifunctional and synergistic physicochemical properties. In particular, heterointerfaces have been at the focal point of nanocatalyst research because the strain caused by lattice mismatches between different phases is the dominant determinant of surface energy and catalytic activity. The ensemble effects of different material phases have also contributed to the interest in heterointerfaced multicomponent materials. Until now, heterointerfaces have largely been regarded as static, and the dynamic movement of components within the multicomponent material phases has received little attention, although the dynamic movement of individual components within multicomponent materials can revise the interpretation of the catalytic behaviors of these materials and lead to fascinating opportunities for nanostructure synthesis. In this study, we demonstrate unprecedented cation migrations within a sulfide matrix induced by surface strain modulation initiated by cation exchange. Specifically, Cu and Ag cations in the sulfide matrix were initially segregated to form a Janus structure. This Janus configuration was then transformed into a core-shell Cu2-xS@Ag2S structure via surface Pt doping. When the surface strain was relieved by a reduced Pt concentration at the nanoparticle surface, the core-shell transitioned back into a Janus structure. We expect that the facile composition fluctuations in multiphasic nanostructures will expand synthetic methodologies for the design and synthesis of intricate nanostructures with useful physicochemical properties.

Neuroprotective Effects of Rasagiline in Parkinson's Disease: A Regional Cerebral Blood Flow Study.

BACKGROUND AND PURPOSE: Despite accumulating evidence for the clinical efficacy and neuroprotective properties of rasagiline in Parkinson's disease (PD), effects of rasagiline on brain perfusion in PD patients have not been elucidated. The present study aimed to investigate the effects of rasagiline on regional cerebral blood flow (rCBF) in patients with PD using single-photon emission computed tomography (SPECT). METHODS: A total of 44 PD patients were recruited and treated with dopamine agonist, either alone or in combination with levodopa. Twenty-two of these patients (referred to as the rasagiline group) additionally received rasagiline (1 mg/day). All patients underwent brain SPECT scans and clinical assessments at baseline and follow-up visits. The mean follow-up period was 2.2 years. Changes in rCBF were compared between the rasagiline group and the comparison group in a voxel-wise manner. RESULTS: Annual change in Unified Parkinson's Disease Rating Scale motor score was lower in the rasagiline group compared to the comparison group (P = .01). A significant group-by-time interaction effect on rCBF was found in the right precuneus (P = .001), where rCBF was decreased in the comparison group and remained stable in the rasagiline group. CONCLUSIONS: Our results show that adjunctive rasagiline treatment had beneficial effects on perfusion in the precuneus of PD patients, suggesting potential neuroprotective effects.

Effects of 6-month at-home transcranial direct current stimulation on cognition and cerebral glucose metabolism in Alzheimer's disease.

BACKGROUND: Although single or multiple sessions of transcranial direct current stimulation (tDCS) on the prefrontal cortex over a few weeks improved cognition in patients with Alzheimer's disease (AD), effects of repeated tDCS over longer period and underlying neural correlates remain to be elucidated. OBJECTIVE: This study investigated changes in cognitive performances and regional cerebral metabolic rate for glucose (rCMRglc) after administration of prefrontal tDCS over 6 months in early AD patients. METHODS: Patients with early AD were randomized to receive either active (n = 11) or sham tDCS (n = 7) over the dorsolateral prefrontal cortex (DLPFC) at home every day for 6 months (anode F3/cathode F4, 2 mA for 30 min). All patients underwent neuropsychological tests and brain 18F-fluoro-2-deoxyglucose positron emission tomography (FDG-PET) scans at baseline and 6-month follow-up. Changes in cognitive performances and rCMRglc were compared between the two groups. RESULTS: Compared to sham tDCS, active tDCS improved global cognition measured with Mini-Mental State Examination (p for interaction = 0.02) and language function assessed by Boston Naming Test (p for interaction = 0.04), but not delayed recall performance. In addition, active tDCS prevented decreases in executive function at a marginal level (p for interaction < 0.10). rCMRglc in the left middle/inferior temporal gyrus was preserved in the active group, but decreased in the sham group (p for interaction < 0.001). CONCLUSIONS: Daily tDCS over the DLPFC for 6 months may improve or stabilize cognition and rCMRglc in AD patients, suggesting the therapeutic potential of repeated at-home tDCS.

A Comparison of Memory Beliefs, Cognitive Activity, and Depression Among Healthy Older Adults, Amnestic Mild Cognitive Impairment, and Patient with Alzheimer's Disease.

BACKGROUND: Amnestic mild cognitive impairment (aMCI) is highly likely to progress to dementia of the Alzheimer type (DAT). One of the most frequently reported symptoms in aMCI and DAT patients is memory impairment. This study compared the levels of beliefs about memory efficacy and control, cognitive activity, and depression among healthy older adults (OA), patients with aMCI, and patients with DAT. METHODS: This study included 21 OA (11 males, 10 females), 16 aMCI patients (6 males, 10 females), and 18 DAT patients (10 males, 8 females). The memory efficacy questionnaire, memory control questionnaire, cognitive activity questionnaire, depression questionnaire, and Seoul Verbal Learning Test were administered to all subjects. RESULTS: DAT patients showed significantly lower scores on the recognition test than did the OA and aMCI patients, and no difference in these scores was observed between the OA and aMCI patients. Regarding the memory efficacy, memory control, and cognitive activity questionnaires, DAT and aMCI patients showed significantly lower scores than did OA. However, there were no differences in these scores between aMCI and DAT patients. CONCLUSION: The results of this study suggest that aMCI patients experienced impairment in memory beliefs and memory control in the same way as DAT patients did. These results suggest that the early application of cognitive rehabilitation therapy for patients with aMCI may be effective in preventing or alleviating memory deterioration.

RuOx-decorated multimetallic hetero-nanocages as highly efficient electrocatalysts toward the methanol oxidation reaction.

Direct methanol fuel cell technology awaits the development of highly efficient and robust nanocatalysts driving the methanol oxidation reaction (MOR) in a CO poisoning-free fashion. Thus far, various Pt-based alloy nanoparticles have been studied as electrocatalysts toward the MOR, and it has been found that the introduction of dopants such as Ru and Cu to Pt has been particularly successful in mitigating the CO poisoning problem. Herein, we report a facile synthesis of Ru-branched RuPtCu nanocages that involves in situ formation of Ru-doped PtCu nanoparticles and subsequent outgrowth of Ru branches by insertion of additional Ru precursors. We show that the electrocatalytic activity and stability of Ru branched RuPtCu ternary nanocages toward the MOR are greatly improved compared to those of PtCu/C and RuPtCu/C counterparts and state-of-the-art PtRu/C and Pt/C catalysts, mainly due to the synergy between the CO-tolerant RuOx phase and the highly open and robust RuPtCu nanoframe.

Janus Nanoparticle Structural Motif Control via Asymmetric Cation Exchange in Edge-Protected Cu1.81S@Ir xS y Hexagonal Nanoplates.

Post-synthetic transformation of nanoparticles has received great attention, because this approach can provide an unusual route to elaborately composition-controlled nanostructures while maintaining the overall structure of the template. In principle, anisotropic heteronanoparticles of semiconductor materials can be synthesized via localized, that is, single site, cation exchange in symmetric nanoparticles. However, the differentiation of multiple identical cation exchange sites in symmetric nanoparticles can be difficult to achieve, especially for semiconductor systems with very fast cation exchange kinetics. We posited that single-site cation exchange in semiconductor nanoparticles might be realized by imposing a significant kinetic hurdle to the cation exchange reaction. The different atomic arrangements of the core and crown in core-crown structures might further differentiate the surface energies of originally identical cation exchange sites, leading to different reactivities of these sites. The first cation exchange site would be highly reactive due to the presence of a formed interface, thereby continuing to act as a site for cation exchange propagation. Herein, we present the proof-of-concept synthesis of Janus nanoparticles by using edge-protected Cu1.81S@Ir xS y hexagonal nanoplates. The Janus nanoparticles comprising {Au2S-Cu1.81S}@Ir xS y or {PdS-Cu1.81S}@Ir xS y exhibited dissimilar structural motifs due to the disparate cation exchange directions. This synthetic methodology exploiting cation exchange of surface-passivated semiconductor nanoparticles could fabricate the numerous symmetry-controlled Janus heterostructures.

Hollow nanoparticles as emerging electrocatalysts for renewable energy conversion reactions.

While the realization of clean and sustainable energy conversion systems primarily requires the development of highly efficient catalysts, one of the main issues had been designing the structure of the catalysts to fulfill minimum cost as well as maximum performance. Until now, noble metal-based nanocatalysts had shown outstanding performances toward the oxygen reduction reaction (ORR), oxygen evolution reaction (OER), and hydrogen evolution reaction (HER). However, the scarcity and high cost of them impeded their practical use. Recently, hollow nanostructures including nanocages and nanoframes had emerged as a burgeoning class of promising electrocatalysts. The hollow nanostructures could expose a high proportion of active surfaces while saving the amounts of expensive noble metals. In this review, we introduced recent advances in the synthetic methodologies for generating noble metal-based hollow nanostructures based on thermodynamic and kinetic approaches. We summarized electrocatalytic applications of hollow nanostructures toward the ORR, OER, and HER. We next provided strategies that could endow structural robustness to the flimsy structural nature of hollow structures. Finally, we concluded this review with perspectives to facilitate the development of hollow nanostructure-based catalysts for energy applications.

A facet-controlled Rh3Pb2S2 nanocage as an efficient and robust electrocatalyst toward the hydrogen evolution reaction.

Highly active and durable electrocatalysts for the hydrogen evolution reaction (HER) may play a pivotal role in commercial success of electrolytic water splitting technology. Among various material classes, binary metal sulphides show a great promise as HER catalysts because of their tunable energy levels conducive to a high catalytic activity and high robustness under harsh operating conditions. On the other hand, facet-controlled nanoparticles with controlled surface energies have gained great recent popularity as active and selective catalysts. However, binary metal sulphide nanoparticles with well-defined facets and high surface areas are very rare. Herein we report the synthesis of a facet-controlled hollow Rh3Pb2S2 nanocage as a new catalytic material and its excellent activity (overpotential: 87.3 mV at 10 mA cm-2) and robustness toward HER under harsh acidic conditions.

Dendrite-Embedded Platinum-Nickel Multiframes as Highly Active and Durable Electrocatalyst toward the Oxygen Reduction Reaction.

Pt-based nanoframe catalysts have been explored extensively due to their superior activity toward the oxygen reduction reaction (ORR). Herein, we report the synthesis of Pt-Ni multiframes, which exhibit the unique structure of tightly fused multiple nanoframes and reinforced by an embedded dendrite. Rapid reduction and deposition of Ni atoms on Pt-Ni nanodendrites induce the alloying/dealloying of Pt and Ni in the overall nanostructures. After chemical etching of Ni, the newly formed dendrite-embedded Pt-Ni multiframes show an electrochemically active surface area (ECSA) of 73.4 m2 gPt-1 and a mass ORR activity of 1.51 A mgPt-1 at 0.93 V, which is 30-fold higher than that of the state-of-the-art Pt/C catalyst. We suggest that high ECSA and ORR performances of dendrite-embedded Pt-Ni multiframes/C can be attributed to the porous nanostructure and numerous active sites exposed on surface grain boundaries and high-indexed facets.

Alignment of Lyotropic Liquid Crystalline Conjugated Polymers in Floating Films.

Directed alignment of polymer chains plays an indispensable role in charge transport properties. We focus not only on a specific method to induce the alignment but also on the design of a liquid crystalline (LC) conjugated polymer to take advantage of an intrinsic self-assembly characteristic. We synthesized a lyotropic LC conjugated polymer, CP1-P, having o-nitrobenzyl (ONB) esters as photocleavable side chains and adopted a floating film transfer method to induce the polymer chain alignment through a lyotropic LC phase transition. An optimum amount of a high boiling point solvent (1,2-dichlorobenzene) in chloroform turned out to be an important factor to maximize the polymer chain alignment. The hole transport mobility along the polymer chain alignment direction was 13-14 times higher than that in the direction perpendicular to the alignment. In addition, the removal of side chains resulted in the solvent resistivity while maintaining the alignment feature in organic thin-film transistors.

Brain Perfusion Correlates of Apathy in Alzheimer's Disease.

BACKGROUND AND PURPOSE: Apathy is one of the most common neuropsychiatric symptoms in patients with Alzheimer's disease (AD). It may have adverse impacts on the progression of AD. However, its neurobiological underpinnings remain unclear. The objective of this study was to investigate differences in regional cerebral blood flow (rCBF) between AD patients with apathy and those without apathy. METHODS: Sixty-six apathetic AD patients and 66 AD patients without apathy completed Neuropsychiatric Inventory (NPI) and underwent technetium-99m hexamethylpropylene amine oxime single-photon emission computed tomography (SPECT) scans. Voxel-wise differences in rCBF between the 2 groups were examined. Association between rCBF and levels of apathy in the apathetic group was also assessed. RESULTS: AD patients with apathy showed lower rCBF in the bilateral orbitofrontal cortex, left putamen, left nucleus accumbens, left thalamus, and bilateral insula than those without (all p<0.005). Mean perfusion across all significant clusters showed a negative linear correlation with NPI apathy score in AD patients with apathy (ß=-0.25; p=0.04). CONCLUSIONS: Hypoperfusion in the prefrontal, striatal, and insular areas may be neural correlates of apathy in AD patients.

Ni@Ru and NiCo@Ru Core-Shell Hexagonal Nanosandwiches with a Compositionally Tunable Core and a Regioselectively Grown Shell.

The development of highly active electrocatalysts is crucial for the advancement of renewable energy conversion devices. The design of core-shell nanoparticle catalysts represents a promising approach to boost catalytic activity as well as save the use of expensive precious metals. Here, a simple, one-step synthetic route is reported to prepare hexagonal nanosandwich-shaped Ni@Ru core-shell nanoparticles (Ni@Ru HNS), in which Ru shell layers are overgrown in a regioselective manner on the top and bottom, and around the center section of a hexagonal Ni nanoplate core. Notably, the synthesis can be extended to NiCo@Ru core-shell nanoparticles with tunable core compositions (Ni3 Cox @Ru HNS). Core-shell HNS structures show superior electrocatalytic activity for the oxygen evolution reaction (OER) to a commercial RuO2 black catalyst, with their OER activity being dependent on their core compositions. The observed trend in OER activity is correlated to the population of Ru oxide (Ru4+ ) species, which can be modulated by the core compositions.

Radially Phase Segregated PtCu@PtCuNi Dendrite@Frame Nanocatalyst for the Oxygen Reduction Reaction.

Pt-based alloy nanoframes have shown great potential as electrocatalysts toward the oxygen reduction reaction (ORR) in fuel cells. However, the intrinsically infirm nanoframes could be severely deformed during extended electro-cyclings, which eventually leads to the loss of the initial catalytic activity. Therefore, the structurally robust nanoframe is a worthy synthetic target. Furthermore, ternary alloy phase electrocatalysts offer more opportunities in optimizing the stability and activity than binary alloy ones. Herein, we report a robust PtCuNi ternary nanoframe, structurally fortified with an inner-lying PtCu dendrite, which shows a highly active and stable catalytic performance toward ORR. Remarkably, the PtCu@PtCuNi catalyst exhibited 11 and 16 times higher mass and specific activities than those of commercial Pt/C.

Iridium-Based Multimetallic Nanoframe@Nanoframe Structure: An Efficient and Robust Electrocatalyst toward Oxygen Evolution Reaction.

Nanoframe electrocatalysts have attracted great interest due to their inherently high active surface area per a given mass. Although recent progress has enabled the preparation of single nanoframe structures with a variety of morphologies, more complex nanoframe structures such as a double-layered nanoframe have not yet been realized. Herein, we report a rational synthetic strategy for a structurally robust Ir-based multimetallic double-layered nanoframe (DNF) structure, nanoframe@nanoframe. By leveraging the differing kinetics of dual Ir precursors and dual transition metal (Ni and Cu) precursors, a core-shell-type alloy@alloy structure could be generated in a simple one-step synthesis, which was subsequently transformed into a multimetallic IrNiCu DNF with a rhombic dodecahedral morphology via selective etching. The use of single Ir precursor yielded single nanoframe structures, highlighting the importance of employing dual Ir precursors. In addition, the structure of Ir-based nanocrystals could be further controlled to DNF with octahedral morphology and CuNi@Ir core-shell structures via a simple tuning of experimental factors. The IrNiCu DNF exhibited high electrocatalytic activity for oxygen evolution reaction (OER) in acidic media, which is better than Ir/C catalyst. Furthermore, IrNiCu DNF demonstrated excellent durability for OER, which could be attributed to the frame structure that prevents the growth and agglomeration of particles as well as in situ formation of robust rutile IrO2 phase during prolonged operation.

Cerebral Perfusion Changes after Acetyl-L-Carnitine Treatment in Early Alzheimer's Disease Using Single Photon Emission Computed Tomography.

BACKGROUND AND PURPOSE: Although acetyl-L-carnitine (ALC) treatment may have beneficial effects on Alzheimer's disease (AD), its underlying neural correlates remain unclear. The purpose of this study was to investigate cerebral perfusion changes after ALC treatment in AD patients using technetium-99m hexamethylpropylene amine oxime single photon emission computed tomography (SPECT). METHODS: A total of 18 patients with early AD were prospectively recruited and treated with ALC at 1.5 g/day for 1.4±0.3 years. At baseline and follow-up, brain SPECT, Mini-Mental State Examination (MMSE), Clinical Dementia Rating (CDR), Global Deterioration Scale (GDS), and Neuropsychiatric Inventory (NPI) were used to assess participants. After ALC administration, changes in brain perfusion, severity of dementia, cognitive performance, and neuropsychiatric disturbances were examined. RESULTS: After ALC administration, changes in scores of MMSE, CDR, GDS, and NPI were not statistically significant (p>0.05). Voxel-wise whole-brain image analysis revealed that perfusion was significantly (p<0.001) increased in the right precuneus whereas perfusion was reduced in the left inferior temporal gyrus (p<0.001), the right middle frontal gyrus (p<0.001), and the right insular cortex (p=0.001) at follow-up. CONCLUSIONS: Although previous studies have suggested that AD patients generally demonstrate progressive deterioration in brain perfusion and clinical symptoms, this study reveals that the perfusion of the precuneus is increased in AD patients after ALC administration and their cognitive and neuropsychiatric symptoms are not aggravated. Further studies are warranted to determine the potential association between perfusion increase in the precuneus and clinical symptoms after ALC treatment in AD patients.