Clinical Significance of Physical Frailty in Subjects With Subjective Cognitive Decline: A Prospective Study With Amyloid PET Data.

BACKGROUND AND PURPOSE: Physical frailty is known to be closely associated with cognitive impairment and to be an early sign of Alzheimer's disease. We aimed to understand the characteristics of physical frailty and define factors associated with physical frailty in subjects with subjective cognitive decline (SCD) by analyzing amyloid data. METHODS: We prospectively enrolled subjects with SCD from a cohort study to identify predictors for the clinical progression to mild cognitive impairment or dementia from SCD (CoSCo). All of the subjects underwent brain magnetic resonance imaging, and brain amyloid positron-emission tomography (PET) to detect amyloid beta plaques. Self-reported exhaustion, handgrip strength, and gait speed were used to measure physical frailty. RESULTS: Of 120 subjects with SCD, 26 (21.7%) were amyloid-positive in PET. Female (odds ratio [OR]=3.79, p=0.002) and amyloid-PET-positive (OR=3.80, p=0.008) subjects with SCD were at high risks of self-reported exhaustion. Amyloid PET positivity (OR=3.22, p=0.047) and high burden from periventricular white-matter hyperintensity (OR=3.34, 95% confidence interval=1.18-9.46, p=0.023) were significantly associated with a weaker handgrip. The subjects with SCD with self-reported exhaustion and weaker handgrip presented with lower cognitive performance in neuropsychological tests, especially for information processing speed and executive function. Subjects with a slower gait performed worse in visual memory function tests. CONCLUSIONS: Amyloid PET positivity was associated with a higher risk of self-reported exhaustion and weaker handgrip in subjects with SCD. The subjects with SCD and physical frailty also performed worse in neuropsychological tests.

Automated brain volumetric program measuring regional brain atrophy in diagnosis of mild cognitive impairment and Alzheimer's disease dementia.

A quantitative analysis of brain volume can assist in the diagnosis of Alzheimer's disease (AD) which is ususally accompanied by brain atrophy. With an automated analysis program Quick Brain Volumetry (QBraVo) developed for volumetric measurements, we measured regional volumes and ratios to evaluate their performance in discriminating AD dementia (ADD) and mild cognitive impairment (MCI) patients from normal controls (NC). Validation of QBraVo was based on intra-rater and inter-rater reliability with a manual measurement. The regional volumes and ratios to total intracranial volume (TIV) and to total brain volume (TBV) or total cerebrospinal fluid volume (TCV) were compared among subjects. The regional volume to total cerebellar volume ratio named Standardized Atrophy Volume Ratio (SAVR) was calculated to compare brain atrophy. Diagnostic performances to distinguish among NC, MCI, and ADD were compared between MMSE, SAVR, and the predictive model. In total, 56 NCs, 44 MCI, and 45 ADD patients were enrolled. The average run time of QBraVo was 5 min 36 seconds. Intra-rater reliability was 0.999. Inter-rater reliability was high for TBV, TCV, and TIV (R = 0.97, 0.89 and 0.93, respectively). The medial temporal SAVR showed the highest performance for discriminating ADD from NC (AUC = 0.808, diagnostic accuracy = 80.2%). The predictive model using both MMSE and medial temporal SAVR improved the diagnostic performance for MCI in NC (AUC = 0.844, diagnostic accuracy = 79%). Our results demonstrated QBraVo is a fast and accurate method to measure brain volume. The regional volume calculated as SAVR could help to diagnose ADD and MCI and increase diagnostic accuracy for MCI.

Delayed Multiple Intracerebral Hemorrhage After Burr Hole Drainage of Chronic Subdural Hematoma During Failure of Warfarin Resumption in Atrial Fibrillation.

Many elderly people take warfarin due to underlying disease. Warfarin is a risk factor for developing chronic subdural hematomas and other intracranial hematomas. Our patient was on chronic warfarin treatment for longstanding atrial fibrillation and underwent burr hole trephination due to chronic subdural hematoma. Multiple intracerebral hemorrhages developed 7 days after surgery without resumption of warfarin. Here, we report and review this rare case.

Impact of the ambulatory blood pressure monitoring profile on cognitive and imaging findings of cerebral small-vessel disease in older adults with cognitive complaints.

We investigated ambulatory blood pressure (BP) monitoring (ABPM) profiles and magnetic resonance imaging (MRI) findings of cerebral small-vessel disease (cSVD) in older adults with cognitive complaints who were grouped as follows: subjective cognitive decline, mild cognitive impairment, and dementia of Alzheimer's type. Group comparisons and correlation analyses among demographic characteristics, cognitive and MRI findings, and ABPM profiles were performed. Furthermore, multivariate logistic regression analyses for dependent variables of (1) dementia or not and (2) MRI criteria of subcortical vascular dementia (SVaD) or not were conducted with independent variables of dichotomized ABPM profiles. A total of 174 subjects (55 males and 119 females) were included: mean age 75.36 ± 7.13 years; Mini-Mental State Examination (MMSE) score 20.51 ± 6.23. No MRI and ABPM findings except medial temporal atrophy were different between three groups. Twenty-four-hour systolic BP (sBP) was correlated with MMSE score (r = -0.182; p = 0.022) and the severity of white matter hyperintensity (WMH) (r = 0.157; p = 0.048). A higher daytime sBP was associated with dementia (odds ratio (OR): 3.734; 95% confidence interval (CI): 1.041-13.390; p = 0.043) and MRI finding of SVaD (OR: 10.543; 95% CI: 1.161-95.740; p = 0.036). Although there were no differences in ABPM profiles between three groups, a higher BP-especially a higher sBP-correlated with cognitive dysfunction and severity of WMH in older adults. Only higher daytime sBP was an independent predictor for dementia and MRI findings of SVaD. Among various ABPM profiles in this study, a higher BP, especially a higher sBP, may be considered the most important for clinical and MRI findings of cSVD.

A Reference-Sampling Based Calibration-Free Fractional-N PLL with a PI-Linked Sampling Clock Generator.

Sampling-based PLLs have become a new research trend due to the possibility of removing the frequency divider (FDIV) from the feedback path, where the FDIV increases the contribution of in-band noise by the factor of dividing ratio square (N2). Between two possible sampling methods, sub-sampling and reference-sampling, the latter provides a relatively wide locking range, as the slower input reference signal is sampled with the faster VCO output signal. However, removal of FDIV makes the PLL not feasible to implement fractional-N operation based on varying divider ratios through random sequence generators, such as a Delta-Sigma-Modulator (DSM). To address the above design challenges, we propose a reference-sampling-based calibration-free fractional-N PLL (RSFPLL) with a phase-interpolator-linked sampling clock generator (PSCG). The proposed RSFPLL achieves fractional-N operations through phase-interpolator (PI)-based multi-phase generation instead of a typical frequency divider or digital-to-time converter (DTC). In addition, to alleviate the power burden arising from VCO-rated sampling, a flexible mask window generation method has been used that only passes a few sampling clocks near the point of interest. The prototype PLL system is designed with a 65 nm CMOS process with a chip size of 0.42 mm2. It achieves 322 fs rms jitter, -240.7 dB figure-of-merit (FoM), and -44.06 dBc fractional spurs with 8.17 mW power consumption.

Impact of an Education Program for Caregivers of Patients with Alzheimer's Disease on Treatment Discontinuation and Compliance in Korea.

BACKGROUND AND PURPOSE: Reportedly 30-50% of patients being treated for chronic illnesses do not adhere to their medication regimen. We assessed the impact of a nurse-led education program for caregivers of Korean de novo Alzheimer's disease patients who had newly been prescribed donepezil. METHODS: This multicenter study analyzed 93 participants in a caregiver education group and 92 participants in a caregiver no-education group. At every visit up to the end of the study (1 year), caregivers in the education group were given educational brochures regarding Alzheimer's disease and the efficacy and adverse events of donepezil treatment. The primary endpoint was the discontinuation rate of donepezil treatment during the 1-year observation period. The secondary endpoints included the effect of education on compliance with donepezil treatment assessed at each visit using a clinician rating scale (CRS) and visual analog scale (VAS), and changes from baseline in cognitive assessment tests. RESULTS: The donepezil discontinuation rates at 1 year were 5.38% (5/93) and 6.52% (6/92) in the caregiver education and no-education groups, respectively (p=0.742). No significant between-group differences in donepezil compliance rates on the CRS and VAS were observed, but significant changes were observed in some cognitive tests from baseline to the end of the study. CONCLUSIONS: Caregiver education had no significant effect on treatment discontinuation, but this may have been due to the low severity of cognitive impairment among the included population at baseline. In addition, the low discontinuation rates meant that no significant difference in treatment compliance was observed.

Discontinuation Rate of Newly Prescribed Donepezil in Alzheimer's Disease Patients in Asia.

BACKGROUND AND PURPOSE: The rate of donepezil discontinuation and the underlying reasons for discontinuation in Asian patients with Alzheimer's disease (AD) are currently unknown. We aimed to determine the treatment discontinuation rates in AD patients who had newly been prescribed donepezil in routine clinical practice in Asia. METHODS: This 1-year observational study involved 38 institutions in seven Asian countries, and it evaluated 398 participants aged 50-90 years with a diagnosis of probable AD and on newly prescribed donepezil monotherapy. The primary endpoint was the rate of donepezil discontinuation over 1 year. Secondary endpoints included the reason for discontinuation, treatment duration, changes in cognitive function over the 1-year study period, and compliance as assessed using a clinician rating scale (CRS) and visual analog scale (VAS). RESULTS: Donepezil was discontinued in 83 (20.9%) patients, most commonly due to an adverse event (43.4%). The mean treatment duration was 103.67 days in patients who discontinued. Among patients whose cognitive function was assessed at baseline and 1 year, there were no significant changes in scores on the Mini-Mental State Examination, Montreal Cognitive Assessment, and Trail-Making Test-Black and White scores, whereas the Clinical Dementia Rating score increased significantly (p<0.001). Treatment compliance at 1 year was 96.8% (306/316) on the CRS and 92.6±14.1% (mean±standard deviation) on the VAS. CONCLUSIONS: In patients on newly prescribed donepezil, the primary reason for discontinuation was an adverse event. Cognitive assessments revealed no significant worsening at 1 year, indicating that continuous donepezil treatment contributes to the maintenance of cognitive function.

Vertebral Artery Dissecting Aneurysm Causing Central Tapia's Syndrome: A Case Report.

The central type of Tapia's syndrome is an extremely rare presentation, characterized by unilateral paralysis of the vagal and hypoglossal nerves, contralateral hemiparesis, or hemihypesthesia. This report describes a case of a middle-aged patient who developed central Tapia's syndrome due to a right vertebral artery dissecting aneurysm (VADA). The patient complained about swallowing difficulty and odynophagia. Right vocal cord paralysis, mild tongue deviation to the right side, left hypesthesia, and decreased temperature sensation with left hemiparesis were observed in neurologic exams. A right VADA and compression of the medulla oblongata due to the VADA were diagnosed on magnetic resonance imaging. Endovascular flow diversion of the right VADA was performed. After 1 year, all neurological symptoms and vocal cord paralysis were nearly resolved, but left hypesthesia remained with decreased nociception. We present and discuss how a VADA caused those symptoms and propose endovascular flow diversion as a treatment option.

Caregiving, care burden and awareness of caregivers and patients with dementia in Asian locations: a secondary analysis.

BACKGROUND: This study investigated the differences in caregiver activity, caregiver burden, and awareness of both caregivers and patients with Alzheimer's disease (AD) across different Asian locations. METHODS: This was a secondary analysis of a multi-national cohort study that aimed to assess caregiver activity and caregiver burden using the Caregiver Activity Scale (CAS) and Zarit Burden Interview (ZBI), respectively. Patients' awareness of their dementia diagnosis was assessed by asking the following yes/no question: "Do you have dementia?" Caregivers' awareness of the patient's dementia diagnosis was assessed by asking the following yes/no question: "Does your patient have dementia?" RESULTS: In total, 524 caregivers of patients with AD from China, Hong Kong, South Korea, the Philippines, Singapore, Thailand, and Taiwan participated. The CAS and ZBI score were significantly different across most locations (p < 0.001 and p = 0.033, respectively). Overall, 56.6% of caregivers and 37.5% of patients had awareness of the dementia diagnosis, and the proportion of patients and caregivers with awareness were also different between each location (all, p < 0.001). CONCLUSIONS: Caregiving, caregiver burden, and the awareness of caregivers and patients were different across many Asian locations. With understanding of cultural differences, further public education on dementia could help increase the awareness of patients and caregivers and reduce caregiver burden. TRIAL REGISTRATION: ClinicalTrials.gov , NCT02262975 . Registered 13 October 2014.

Acute Quadriplegia after Lumbar Puncture in a Patient with Misdiagnosed Cervical Myelopathy.

The incidence of quadriplegia following drainage of cerebrospinal fluid by lumbar puncture (LP) below a spinal occupying lesion is rare. We report a case of acute quadriplegia following LP for presumed normal pressure hydrocephalus (NPH) in a 66-year-old man. Acute cervical myelopathy with a herniated cervical disc was subsequently found on magnetic resonance imaging (MRI) at the C5-6 level. After posterior decompression and anterior cervical discectomy and fusion at the C5-6 level with a cervical plate, the patient's motor and sensory functions recovered. Clinicians should be aware that symptoms of NPH and cervical myelopathy may overlap, and that serious complications may occur when performing LP below a spinal lesion. As a safety measure, cervical spine MRI should be performed before LP.

Microsurgical treatment for the recurrent cerebral aneurysm initially treated using coil embolization.

OBJECTIVE: Microsurgical treatment could be a good alternative for the treatment of recurrent cerebral aneurysm after coil embolization. The purpose of this study was to present our experience of microsurgical treatment for recurrent cerebral aneurysm previously treated using coil embolization. METHODS: From June 2012 to May 2019, 34 patients consecutively received microsurgical treatment for a recurrent cerebral aneurysm previously treated using coil embolization after it ruptured. RESULTS: Of the 34 patients with aneurysm, 33 had the aneurysm located in the anterior circulation. The most common location was the anterior communicating artery (13 cases). Immediate radiologic outcome at coil embolization was completed (n=6), residual neck (n=26), and residual sac (n=2). The reason for microsurgical treatment included rebleeding (n=12), persistent residual sac (n=1), and recurrence on follow-up study (n=21). Rebleeding occurred within 10 days after coil embolization in 10 cases, and the other 2 were due to regrowth. In the 20 recurred and saccular aneurysms, coil compaction was present in 11 aneurysms and regrowth in 9 aneurysms. Simple neck clipping (n=29) and clipping with coil mass extraction (n=3) was possible in the saccular aneurysms. The blood blister like aneurysm (n=2) were treated using bypass and endovascular internal carotid artery trapping. In the follow-up study group after microsurgical treatment there were no severe complications due to the treatment. Age, cause of retreatment, and modified Rankin Scale before microsurgery were associated with good outcome (p<0.001). CONCLUSIONS: Microsurgical treatment may be a viable and effective option for treating recurrent aneurysms previously treated by endovascular techniques.

Analysis of Neuropsychiatric Symptoms in Patients with Alzheimer's Disease Using Quantitative EEG and sLORETA.

OBJECTIVE: The electrocortical activities associated with the neuropsychiatric symptoms (NPSs) of Alzheimer's disease (AD) were investigated using frequency-domain electroencephalography (EEG) spectral source analysis, and the potential electrocortical indices identified. MATERIALS AND METHODS: Scalp EEG data were obtained from 51 patients with AD to investigate the presence of four NPS subdomains, hyperactivity, psychosis, affective symptoms, and apathy. EEG power spectra and the standardized low-resolution brain electromagnetic tomography (sLORETA)-localized EEG cortical sources were compared between the groups with and without the four NPS subdomains in eight frequency bands: 1-4, 4-8, 8-10, 10-12, 12-18, 18-20, 20-30, and 30-45 Hz. RESULTS: The power spectral analysis of EEG data showed that AD patients with psychosis had lower values at the α2-band in most areas. In patients with apathy, the θ-to-ß power ratio showed a greater activity over the frontal and central regions. The cortical source analysis using sLORETA revealed that patients with psychosis showed decreased values in the α2-band and patients with apathy showed higher δ-values, especially in the right frontal and temporal regions. CONCLUSION: The results of the present study showed that both classical EEG spectral and EEG source analysis could differentiate patients with and without NPSs, especially psychosis and apathy subdomains. Spectral and sLORETA analyses provided information helpful for a better characterization in patients with NPSs.

A comparison of sociobehavioral impact on cognitive preservation in Alzheimer's disease between Taiwan and Korea: A cross-national study.

Both Taiwan and Korea are developed countries with different cultures. When encountering the issue of dementia, such sociobehavioral factors have various and different impacts on dementia. We aim to assess the cross-national difference of sociobehavioral impact on cognitive preservation in Alzheimer's disease (AD) between Taiwan and Korea.A uniformed data set was administered regarding AD. We evaluated annual cognitive function using the Mini-Mental State Examination (MMSE), Clinical Dementia Rating sum of box (CDR-SB), and CDR for 2 continuous years. Annual change of scores compared with the baseline indicated cognitive change as preservation or decline. We recorded the sociodemographic variables of interest, including education duration, level of independence, living situation, and marital status. Step-wise regression analyses were performed to determine the independent factors for cognitive preservation.In total, 503 participants in Taiwan and 77 participants in Korea were recruited from 2011 to 2014. The baseline demographic characteristics were different in levels of education, living situation, level of independence, and dementia severity between the 2 countries. With follow-up for 2 years, cognitive preservation was associated with CDR staging at baseline and independence [adjusted odds ratio (OR) = 1.657, 95% confidence interval (95% CI) = 1.109-2.477, P = .014] in the Taiwanese population, whereas cognitive preservation was related to living alone (adjusted OR = 3.316, 95% CI = 1.135-9.687, P = .028) in the Korean population. The levels of education showed inconsistency in cognitive preservation in both countries.Cognitive preservation was associated with independence in the Taiwanese population, whereas cognitive preservation was related to living alone in the Korean population. By practicing relevant socioeconomic support, this might contribute to lessening the negative impact of dementia and preserving cognition in different countries.

Coexistence of Cerebral Microbleeds and Amyloid Pathology in Patients with Cognitive Complaints.

BACKGROUND AND PURPOSE: We investigated the prevalence of amyloid positivity and cerebral microbleeds (CMBs) in subjects with cognitive complaints with the aim of identifying differences in clinical parameters and cognitive function according to the pattern of coexistence. METHODS: We retrospectively enrolled 200 subjects with memory impairment and applied both standardized ¹8F-florbetaben PET and brain MRI, including susceptibility-weighted imaging. The amyloid burden was visually classified as positive or negative, and the number and location of CMBs were also analyzed visually. Descriptive analysis was performed for the prevalence of amyloid positivity and CMBs. The relationship between the coexisting pattern of those two findings and clinical parameters including the results of neuropsychiatric tests was analyzed. RESULTS: Positive amyloid PET scans were exhibited by 102 (51.5%) of the 200 patients, and 51 (25.5%) of them had CMBs, which were mostly located in lobar areas in the patients with positive amyloid scans. The patients with CMBs were older and had a higher burden of white-matter hyperintensities than the patients without CMBs. The patients with CMBs also performed worse in confrontation naming and frontal/executive function. When classified by topographical region, parietal CMBs (odds ratio=3.739, p=0.024) were significantly associated with amyloid positivity. CONCLUSIONS: The prevalence of CMBs was higher in patients with cognitive decline than in the general population. CMBs play distinctive roles in affecting clinical parameters and neuropsychological profiles according to the coexistence of amyloid pathology.

Burr Hole Drainage versus Small Craniotomy of Chronic Subdural Hematomas.

OBJECTIVE: Chronic subdural hematoma drainage is one of the most common procedures performed in neurosurgical practice. Not only burr hole drainage but also small craniotomy (diameter 3-5 cm) is frequently used neurosurgical treatment of chronic subdural hematomas. We assessed to compare the postoperative recurrence rates between burr hole drainage versus small craniotomy with closed-system drainage for chronic subdural hematomas. METHODS: From January 2016 to December 2018, 75 patients who were treated with burr hole drainage and small craniotomy with closed system drainage for the symptomatic chronic subdural hematoma were enrolled. Pre and postoperative computed tomography (CT) were used for radiologic evaluation. The choice of procedure was decided by preoperative CT images. RESULTS: 60 patients out of 75 patients underwent burr hole drainage, whereas 15 patients underwent small craniotomy. The overall postoperative recurrence rate was 16%. The recurrence occurred in 8 patients out of 60 patients in burr hole drainage group (13.3%) and 7 patients out of 15 patients in small craniotomy group (46.7%). The number of days of hospitalization was 10.3 days in burr hole drainage group and 15.7 days in small craniotomy group. CONCLUSION: Burr hole drainage would be sufficient to evacuate chronic subdural hematoma with lower recurrence rate, but small craniotomy was also needed in some cases such as hematoma has solid portion or multiple septum.

Prediction of cognitive impairment via deep learning trained with multi-center neuropsychological test data.

BACKGROUND: Neuropsychological tests (NPTs) are important tools for informing diagnoses of cognitive impairment (CI). However, interpreting NPTs requires specialists and is thus time-consuming. To streamline the application of NPTs in clinical settings, we developed and evaluated the accuracy of a machine learning algorithm using multi-center NPT data. METHODS: Multi-center data were obtained from 14,926 formal neuropsychological assessments (Seoul Neuropsychological Screening Battery), which were classified into normal cognition (NC), mild cognitive impairment (MCI) and Alzheimer's disease dementia (ADD). We trained a machine learning model with artificial neural network algorithm using TensorFlow (https://www.tensorflow.org) to distinguish cognitive state with the 46-variable data and measured prediction accuracies from 10 randomly selected datasets. The features of the NPT were listed in order of their contribution to the outcome using Recursive Feature Elimination. RESULTS: The ten times mean accuracies of identifying CI (MCI and ADD) achieved by 96.66 ± 0.52% of the balanced dataset and 97.23 ± 0.32% of the clinic-based dataset, and the accuracies for predicting cognitive states (NC, MCI or ADD) were 95.49 ± 0.53 and 96.34 ± 1.03%. The sensitivity to the detection CI and MCI in the balanced dataset were 96.0 and 96.0%, and the specificity were 96.8 and 97.4%, respectively. The 'time orientation' and '3-word recall' score of MMSE were highly ranked features in predicting CI and cognitive state. The twelve features reduced from 46 variable of NPTs with age and education had contributed to more than 90% accuracy in predicting cognitive impairment. CONCLUSIONS: The machine learning algorithm for NPTs has suggested potential use as a reference in differentiating cognitive impairment in the clinical setting.

Hyaluronic Acid-Conjugated with Hyperbranched Chlorin e6 Using Disulfide Linkage and Its Nanophotosensitizer for Enhanced Photodynamic Therapy of Cancer Cells.

The main purpose of this study is to synthesize novel types of nanophotosensitizers that are based on hyperbranched chlorin e6 (Ce6) via disulfide linkages. Moreover, hyperbranched Ce6 was conjugated with hyaluronic acid (HA) for CD44-receptor mediated delivery and redox-sensitive photodynamic therapy (PDT) against cancer cells. Hyperbranched Ce6 was considered to make novel types of macromolecular photosensitizer since most of the previous studies regarding nanophotosensizers are concerned with simple conjugation between monomeric units of photosensitizer and polymer materials. Hyperbranched Ce6 was synthesized by conjugation of Ce6 each other while using disulfide linkage. To synthesize Ce6 tetramer, carboxyl groups of Ce6 were conjugated with cystamine and three equivalents of Ce6 were then conjugated again with the end of amine groups of Ce6-cystamine. To synthesize Ce6 decamer as a hyperbranched Ce6, six equivalents of Ce6 was conjugated with the end of Ce6 tetramer via cystamine linkage. Furthermore, HA-cystamine was attached with Ce6 tetramer or Ce6 decamer to synthesize HA-Ce6 tetramer (Ce6tetraHA) or HA-Ce6 decamer (Ce6decaHA) conjugates. Ce6tetraHA and Ce6decaHA nanophotosensitizers showed small diameters of less than 200 nm. The addition of dithiothreitol (DTT) and hyaluronidase (HAse) induced a faster Ce6 release rate in vitro drug release study, which indicated that Ce6tetraHA nanophotosensitizers possess redox-sensitive and HAse-sensitive release properties. Ce6tetraHA nanophotosensitizers showed higher intracellular Ce6 accumulation, higher ROS generation, and higher PDT efficacy than that of Ce6 alone. Ce6tetraHA nanophotosensitizers responded to the CD44 receptor of cancer cell surface, i.e., the pre-treatment of HA blocked CD44 receptor of U87MG or HCT116 cells and then inhibited delivery of nanophotosensitizers in vitro cell culture study. Furthermore, in vivo tumorxenograft study showed that fluorescence intensity in the tumor tissues was stronger than those of other organs, while CD44 receptor blocking by HA pretreatment induced a decrease of fluorescence intensity in tumor tissues when compared to liver. These results indicated that Ce6tetraHA nanophotosensitizers delivered to tumors by redox-sensitive and CD44-sensitive manner.