Suggestions on the ideal method of conducting community screenings for older adults.

BACKGROUND/OBJECTIVES: Since dementia and frailty lead to a reduced quality of life and risk of needing long-term care in the older adults, we hypothesized that evaluations related to dementia and frailty would be useful and of high interest in screening for the older adults. Therefore, we conducted a community screening incorporating multiple simple evaluations related to dementia and frailty. In addition to various functional evaluations, we investigated interest in tests, thoughts on the disease, and the relationships between subjective (i.e., how one feels about oneself) and objective evaluations (i.e., the results of tests and rating scales). The purpose of this study was to examine the thoughts regarding tests and diseases and the functions that make it difficult to accurately perceive changes by oneself, and to obtain suggestions on the ideal method of community screening for the older adults. SUBJECTS/METHODS: The participants were 86 people aged 65 and over living in Kotoura Town who participated in the community screening, for which we obtained background information and body measurements. We also assessed physical, cognitive and olfactory function, evaluated nutritional status, and we administered a questionnaire (interest in tests, thoughts on dementia and frailty, and a subjective functional evaluation). RESULTS: Regarding interest in tests, the participants answers were highest for physical, cognitive and olfactory function, in that order (68.6%, 60.5%, and 50.0%, respectively). In the survey on thoughts on dementia and frailty, 47.6% of participants felt that people with dementia were viewed with prejudice, and 47.7% did not know about frailty. Regarding the relationship between subjective and objective evaluations, only the assessment of cognitive function did not show a correlation between both evaluations. CONCLUSIONS: From the viewpoint of the participants' degree of interest in and the need for accurate evaluations through objective examination, the findings suggest that the assessment of physical and cognitive function may be beneficial as a screening tool for older adults. Objective evaluation is essential, particularly for assessing cognitive function. However, approximately half the participants believed people with dementia were viewed with prejudice and did not know about frailty, which may lead to barriers to testing and low interest. The importance of increasing the participation rate in community screening through disease-related educational activities was suggested.

Validation of a novel computerized cognitive function test for the rapid detection of mild cognitive impairment.

BACKGROUND: In the present study, we examined the distinguishing ability of a mild cognitive impairment (MCI) assessment tool for rapid screening using a computer (MARC) for Alzheimer's disease dementia (ADD), MCI, and non-demented controls (NDC) with no cognitive impairment, as well as its validity and reliability, as part of a preliminary trial for the development of the tool. METHODS: A total of 64 participants (23 in the ADD group, 17 in the MCI group, and 24 in the NDC group) were analyzed. The participants were administered MARC and a pre-existing computerized Alzheimer's dementia screening test (MSP), and 31 participants (14 in the MCI group, 17 in the NDC group) were readministered MARC within 4 months from the first test. RESULTS: The median (interquartile range) test time for MARC was 401 (350-453) s. Total MARC scores were significantly worse in the MCI and ADD groups than in the NDC group (p < 0.05 and p < 0.01, respectively). In the receiver operating characteristic (ROC) analysis, the area under the ROC curve (AUC) when comparing the NDC and MCI groups was 0.866 (95% CI, 0.759-0.974), when comparing the NDC and AD groups was 0.989 (95% CI, 0.970-1.000), and when comparing the MCI and AD groups was 0.889 (95% CI, 0.790-0.988). Furthermore, there was a significant correlation with the results of the existing test, MSP (r = 0.839, p < 0.001). In addition, the intraclass correlation coefficient (ICC) (1,1) when the first and second MARC scores were compared was 0.740 (95% CI, 0.529-0.865; p < 0.001). CONCLUSIONS: MARC is considered capable of distinguishing MCI with high accuracy. The tool has good validity and reliability, and it can be administered in a short period of time without the need for a specialist.

Verification of the association between cognitive decline and olfactory dysfunction using a DEmentia screening kit in subjects with Alzheimer's dementia, mild cognitive impairment, and normal cognitive function (DESK study): A multicenter, open-label, interventional study.

Background and purpose: Olfactory dysfunction may be an early symptom of degenerative neurological disorders such as mild cognitive impairment (MCI), which may progress to cognitive decline and Alzheimer's disease (AD). We investigated the relationship between cognitive decline and olfactory dysfunction in healthy controls and patients with MCI or AD using the DEmentia Screening Kit (DESK), an olfactory identification assessment tool designed for Japanese populations. Methods: In this multicenter, open-label, interventional study conducted from 16 September 2020 to 30 April 2021, participants underwent olfactory tests using the DESK tool. This included 10 odorants at two concentrations (weak/strong) including toothpaste, butter, and India ink. Results: Among 223 participants, 100, 61, and 62 were healthy controls, MCI patients, and AD patients (mean ages, 57.4, 72.8, and 76.3 years; total DESK olfaction scores, 18.4, 14.7, and 7.4), respectively. Significant differences in total olfaction scores were observed between groups (healthy controls vs MCI, healthy controls vs AD, and MCI vs AD). Significant between-group total score differences were shown for olfaction scores with both the 10 strong and 10 weak odorant varieties. Conclusion: The DESK tool may discriminate between healthy individuals and those with MCI or AD, facilitating early screening for cognitive decline among Japanese patients, although the effect of age on DESK olfaction scores has not been fully explored.

Association between frequency of going out and mild cognitive impairment in community-dwelling older adults: a pilot study in frailty prevention groups.

BACKGROUND: Clarifying the role of physical limitations in the relationship between frequency of going out and mild cognitive impairment (MCI) may be useful in supporting early detection and prevention of MCI. However, few studies have explored relatively active populations that are continuously active throughout the year. This study aimed to determine the relationship between frequency of going out and MCI among non-homebound older adults who participated in group activities to prevent frailty. METHODS: This prospective cohort study used frequency of going out as the exposure and MCI as the outcome. The Touch Panel-type Dementia Assessment Scale and questionnaires about daily life were completed by 153 community-dwelling older adults aged ≥65 years participating in frailty prevention groups in a rural town. The baseline survey was conducted from December 2017 to March 2018 and analysed cross-sectionally. Follow-up surveys were conducted at 1- and 2-years and analysed longitudinally. RESULTS: Univariate and binomial logistic regression analyses at baseline showed no association between MCI and frequency of going out in older adults with physical limitations. However, there was a significant association in older adults without physical limitations. A binomial logistic regression analysis of the frequency of going out at baseline and cognitive function at the 2-year follow-up showed no association between MCI and frequency of going out in older adults with physical limitations, but there was a significant association in those without physical limitations. CONCLUSION: Our results suggest that frequency of going out may not be a useful indicator of MCI in older adults with physical limitations, although low frequency of going out may be an indicator of MCI in older adults without physical limitations.

Dementia Prevention and Aromatherapy in Japan.

Until recently, it was thought that dementia prevention was not possible. However, a recent paper reported that 40% of the risk factors for developing dementia are modifiable. Large-scale clinical studies on dementia prevention and various initiatives to reduce the risk of developing dementia have been made worldwide. In addition to the introduction of a global initiative in dementia prevention, I also introduce the results of our research on the development of the Tottori method dementia prevention program and aromatherapy to approach olfactory impairment in Alzheimer's disease.

Examination of the cognitive function of Japanese community-dwelling older adults in a class for preventing cognitive decline during the COVID-19 pandemic.

We examined the changes in cognitive function due to restrictions in daily life during the coronavirus disease 2019 (COVID-19) pandemic in community-dwelling older adults with mild cognitive decline. This was a retrospective, case-control study. The participants include 88 older adults with mild cognitive decline (mean age = 81.0 [standard deviation = 6.5] years) who participated in a class designed to help prevent cognitive decline. This class was suspended from early-March to end of May 2020 to prevent the spread of COVID-19, and resumed in June 2020. We collected demographic and cognitive function test data (Touch Panel-type Dementia Assessment Scale [TDAS]) before and after class suspension and questionnaire data on their lifestyle and thoughts during the suspension. Change in TDAS scores from before and after the suspension was used to divide the participants into decline (2 or more points worsening) and non-decline (all other participants) groups, with 16 (18.2%) and 72 (81.8%) participants in each group, respectively. A logistic regression model showed that the odds ratio (OR) for cognitive decline was lower in participants whose responses were "engaged in hobbies" (OR = 0.07, p = 0.015), "worked on a worksheet about cognitive training provided by the town hall" (OR = 0.19, p = 0.026), and "had conversations over the phone" (OR = 0.28, p = 0.0495). There was a significant improvement in TDAS scores after class was resumed (p < 0.01). A proactive approach to intellectual activities and social ties may be important for the prevention of cognitive decline during periods of restrictions due to COVID-19. We found that cognitive function test scores before class suspension significantly improved after resuming classes. We speculate that continued participation in this class led to positive behavioral changes in daily life during periods of restriction due to COVID-19.

Cognitive Improvement and Safety Assessment of a Dietary Supplement Containing Propolis Extract in Elderly Japanese: A Placebo-Controlled, Randomized, Parallel-Group, Double-Blind Human Clinical Study.

Objectives. This study aimed to evaluate the effect of propolis on cognitive function in elderly Japanese with a placebo-controlled design. Material and Methods. This study was performed on 79 elderly Japanese. Participants orally received either a placebo or dietary supplement containing propolis extract for 24 weeks. Cognitive function assessed by Cognitrax and various blood or urine markers were measured at pre- and postadministration. Results and Conclusion. Eligible data from 68 subjects (placebo: 33, propolis: 35) who completed the study were analyzed. Compared to the placebo group, the propolis group showed significant improvement in verbal memory in Cognitrax (P=0.028). Total cholesterol, LDL cholesterol, urea nitrogen, creatinine, and uric acid were significantly improved in the propolis group compared to the placebo group (P = 0.011, P = 0.004, P = 0.048, P = 0.045, and P = 0.005, respectively). However, urea nitrogen, creatinine, and uric acid fluctuated within the normal level. Furthermore, a subgroup analysis was performed on those with higher than 100 of the standardized score of the neurocognitive index indicated by the overall Cognitrax score. Significant improvements in the propolis group compared to placebo were confirmed in verbal memory (P = 0.007) and processing speed as indications for information processing ability, complex attention, and concentration (P = 0.029). No side effects were observed in any of the groups. This study demonstrates that propolis is effective in improving cognitive functions such as memory, information processing, complex attention, and concentration in elderly Japanese.

Aromatherapy improves cognitive dysfunction in senescence-accelerated mouse prone 8 by reducing the level of amyloid beta and tau phosphorylation.

Alzheimer's disease (AD) is a progressive neurodegenerative disease and is known to be the most common cause of dementia. We previously described the benefits of aromatherapy on the cognitive function of patients with AD utilizing various aromatic essential oils; however, its mechanism of action remains poorly understood. Consequently, in the present study, this mechanism was thoroughly evaluated employing a dementia mice model, specifically the senescence-accelerated mouse prone 8. The mice were exposed to a mixture of lemon and rosemary oil at nighttime as well as to a mixture of lavender and orange oil in the daytime for 2 months. The cognitive function of the mice was assessed before and after treatment with the aromatic essential oils using the Y-maze test. Moreover, the brain levels of amyloid beta (Aß), abnormally phosphorylated tau, and brain-derived neurotrophic factor (BDNF) were measured following treatment. The benefits of aromatherapy on the cognitive function in mice were confirmed. It was also established that the brain levels of Aß and abnormally phosphorylated tau were considerably lower in the aromatherapy group, while the levels of BDNF were marginally higher. These results suggest that aromatherapy employing these aromatic essential oils is beneficial for the prevention and treatment of AD.

Detection and recognition thresholds for five basic tastes in patients with mild cognitive impairment and Alzheimer's disease dementia.

BACKGROUND: Patients with Alzheimer's disease dementia (ADD) are thought to exhibit taste disorders; however, this has not been extensively studied. We investigated gustatory functions and factors affecting taste in patients with ADD or mild cognitive impairment (MCI) and in non-demented controls (NDCs) and evaluated associations between cognitive impairment and gustatory functions. METHODS: We recruited 29 patients with ADD, 43 with MCI, and 14 with NDCs. We obtained medical and medication history, measured salivary secretion volumes, and performed cognitive function tests, blood tests, whole-mouth gustatory tests, and dietary and gustatory questionnaires. RESULTS: Patients with ADD showed significantly higher recognition threshold values than NDCs (p < 0.05). Many individuals did not recognize umami at the maximum concentration, and this happened more frequently in patients with ADD or MCI than in NDCs. Evaluation items other than cognitive function tests did not show significant differences among the groups, but many individuals had decreased salivation, low serum zinc levels, and were on multiple medications. We found a significant correlation between recognition threshold and age (r = 0.229, p < 0.05) and cognitive function test score (r = 0.268, p < 0.05). CONCLUSIONS: Patients with ADD showed impairment of gustatory function. Gustatory impairment in patients with MCI could not be confirmed. However, many individuals with MCI did not recognize umami, either. Our results suggest that taste disorders in elderly people with cognitive decline occur independently of factors affecting taste such as salivation, zinc levels, or prescription drugs. TRIAL REGISTRATION: The study was registered in the UMIN Clinical Trials Registry on February 10, 2017, with reference number UMIN000026087.

A program of exercise, brain training, and lecture to prevent cognitive decline.

OBJECTIVE: We examined the benefits of a community-based program combining physical exercise, cognitive training, and education on dementia and lifestyle habits. METHODS: This crossover open-label trial included 141 community-dwelling elderly people with suspected mild cognitive decline (MCD). Subjects were assigned to a 6-month intervention-first/6-month observation-second (INT-OBS) group or an OBS-INT group. The 6-month intervention consisted of 2 h of physical exercise, cognitive training, and classroom study or rest once weekly. Primary outcome was change in Touch Panel-type Dementia Assessment Scale (TDAS) score. RESULTS: TDAS score improved significantly during the intervention period compared with the observation period for all subjects (P < 0.05). Some physical functions also improved significantly during the intervention period compared with the observation period in the OBS-INT group (P < 0.05). INTERPRETATION: This community-based program improved both cognitive and physical function in elderly people with suspected MCD.

Evaluation of the effect of aroma oil as a bath salt on cognitive function.

BACKGROUND: Aromatherapy is a non-pharmacological therapy for the improvement of dementia symptoms. This study aimed to assess the effects of aroma oil as a bath salt on cognitive function, olfactory function and sleep quality. METHODS: This was a randomised controlled trial. Overall, 49 patients were able to provide consent, and 35 were finally analysed (Alzheimer's disease: 10, mild cognitive impairment: 25). The patients were randomly assigned to use 0.1%, 0.5% or 1% aroma bath salt. During daily bathing, bath salt was added to the bath water, and the subjects remained in the bathroom for ≥10 min. The intervention period was 24 weeks, and the observation periods were 4 weeks before and after using the aroma bath salt. We performed the Touch Panel-type Dementia Assessment Scale (TDAS), the Odour Stick Identification Test for Japanese (OSIT-J) and the Japanese version of the Pittsburgh Sleep Quality Index (PSQI-J) five times during the before and after observation periods and after the 12-week intervention. RESULTS: There were no significant changes in the TDAS, OSIT-J and PSQI-J scores before and after the intervention in all groups. Moreover, there were no significant differences in the TDAS, OSIT-J and PSQI-J scores between the groups before and after the intervention. In the correlation analysis of changes in the TDAS and other tests during the intervention period, significant associations between TDAS and sleep latency and sleep disturbances, which are sub-items of PSQI-J, were observed in the use of 0.1% aroma bath salt group. CONCLUSIONS: The use of aroma bath salt was not associated with improvement in cognitive function, olfactory function or sleep quality. However, sleep-related aspects were associated with changes in cognitive function before and after use of aroma bath salt, which suggested that there is a link between improvements in sleep and that in cognitive function.

How the Post-Fracture Rehabilitation Choice Affects Brain Function in Older People?

BACKGROUND: We investigated how the type of rehabilitation affects brain function and antioxidant potential. METHODS: Twenty-eight patients hospitalized for fall-related fractures were assigned to either a physical therapy group or an occupational therapy group. Cognition was assessed using the Touch Panel-type Dementia Assessment Scale (TDAS) and oxidative stress with serum pentosidine levels. Spectral analysis and coherence analysis were also performed. RESULTS: Changes in TDAS scores and serum pentosidine levels did not differ significantly between the 2 therapies. Power spectral analysis revealed a significant intergroup difference in δ waves. Coherence analysis showed significant intergroup differences in the activities of δ waves and ß waves. CONCLUSIONS: Cognitive function and antioxidant potential did not differ between the 2 types of rehabilitation. However, the impact on cerebral neuronal activity may have differed.

Post-fracture Rehabilitation Effects on Brain Function in Older People.

BACKGROUND: Deterioration of cognitive function is an underlying cause of older people's fractures. The purpose of this study was to evaluate electroencephalogram and cognitive function in patients hospitalized with fractures, both at admission (before intervention) and at the time of discharge (after intervention), to investigate the effects of rehabilitation on brain function. METHODS: A total of 24 patients hospitalized with fracture due to a fall were enrolled in this study. All the subjects received 140 minutes of rehabilitation every day during hospitalization. Touch Panel-type Dementia Assessment Scale (TDAS) was used to test their cognitive function. In electroencephalography (EEG), the Neuronal Activity Topography (NAT) system was used to calculate the "Alzheimer's disease (AD) - normal controls (NLc) differential similarity" in sNAT, ie, a numerical index to show the proximity to AD or normal NLc. RESULTS: There was no significant difference in the total TDAS score among subjects who were examined before and after intervention, but 12 subjects who were observed with deterioration of cognitive functionat at before intervention had a significant improvement in "word-recognition," a sub-item in TDAS (P < 0.05). In addition, the NAT analysis findings showed that the differential similarity in sNAT significantly approached the NLc pattern (P < 0.05). CONCLUSION: EEGs in patients with fractures resulting from a fall became more similar to NL patterns at the time of discharge. In addition, recent-memory function of patients who had decline in cognitive function improved.

Effect of monosodium L-glutamate (umami substance) on cognitive function in people with dementia.

BACKGROUND/OBJECTIVES: This study assessed the effect of continuous ingestion of monosodium L-glutamate (MSG) on cognitive function and dietary score in dementia patients. SUBJECTS/METHODS: This was a single-blind, placebo-controlled trial involving 159 subjects with dementia residing in a hospital or nursing home. We assigned the subjects to a group that ingested MSG thrice daily (0.9 g/dose) (MSG group; n = 79) or a group that ingested NaCl thrice daily (0.26 g/dose) (Control group; n = 80). This study consisted of a 12-week intake period, followed by a 4-week follow-up period without the ingestion of MSG or NaCl. We performed physical examination, cognitive symptom tests (the Touch Panel-type Dementia Assessment Scale (TDAS) and Gottfries-Bråne-Steen Scale (GBSS)), palatability and behaviour questionnaires, and blood tests before and after the intervention and after the follow-up period. RESULTS: There were no significant differences in the TDAS and GBSS total scores between the groups before and after the intervention. However, regarding the TDAS sub-items, "the accuracy of the order of a process" did not deteriorate in the MSG group compared with that observed in the Control group (p < 0.05). At the follow-up assessment, the TDAS total scores in the MSG group showed significant improvement compared with those reported in the Control group (p < 0.05). Furthermore, there was a correlation of changes from pre-intervention to post-intervention between the TDAS and enjoyment of the meal (r = -0.299, p = 0.049). CONCLUSIONS: Our results suggest that continued ingestion of MSG has an effect on cognitive function. Furthermore, the patients with improved questionnaires about palatability survey showed greater improvement in cognitive function.

123I-MIBG myocardial scintigraphy for the diagnosis of DLB: a multicentre 3-year follow-up study.

BACKGROUND AND PURPOSE: We previously reported the usefulness of iodine-123 metaiodobenzylguanidine (123I-MIBG) myocardial scintigraphy for differentiation of dementia with Lewy bodies (DLB) from Alzheimer's disease (AD) in a cross-sectional multicentre study. The aim of this study was, by using reassessed diagnosis after 3-year follow-up, to evaluate the diagnostic accuracy of 123I-MIBG scintigraphy in differentiation of probable DLB from probable AD. METHODS: We undertook 3-year follow-up of 133 patients with probable or possible DLB or probable AD who had undergone 123I-MIBG myocardial scintigraphy at baseline. An independent consensus panel made final diagnosis at 3-year follow-up. Based on the final diagnosis, we re-evaluated the diagnostic accuracy of 123I-MIBG scintigraphy performed at baseline. RESULTS: Sixty-five patients completed 3-year follow-up assessment. The final diagnoses were probable DLB (n=30), possible DLB (n=3) and probably AD (n=31), and depression (n=1). With a receiver operating characteristic curve analysis of heart-to-mediastinum (H/M) ratios for differentiating probable DLB from probable AD, the sensitivity/specificity were 0.77/0.94 for early images using 2.51 as the threshold of early H/M ratio, and 0.77/0.97 for delayed images using 2.20 as the threshold of delayed H/M ratio. Five of six patients who were diagnosed with possible DLB at baseline and with probable DLB at follow-up had low H/M ratio at baseline. CONCLUSIONS: Our follow-up study confirmed high correlation between abnormal cardiac sympathetic activity evaluated with 123I-MIBG myocardial scintigraphy at baseline and the clinical diagnosis of probable DLB at 3-year follow-up. Its diagnostic usefulness in early stage of DLB was suggested. TRIAL REGISTRATION NUMBER: UMIN00003419.

Comparative analysis of cerebrospinal fluid metabolites in Alzheimer's disease and idiopathic normal pressure hydrocephalus in a Japanese cohort.

BACKGROUND: Alzheimer's disease (AD) is a most common dementia in elderly people. Since AD symptoms resemble those of other neurodegenerative diseases, including idiopathic normal pressure hydrocephalus (iNPH), it is difficult to distinguish AD from iNPH for a precise and early diagnosis. iNPH is caused by the accumulation of cerebrospinal fluid (CSF) and involves gait disturbance, urinary incontinence, and dementia. iNPH is treatable with shunt operation which removes accumulated CSF from the brain ventricles. METHODS: We performed metabolomic analysis in the CSF of patients with AD and iNPH with capillary electrophoresis-mass spectrometry. We assessed metabolites to discriminate between AD and iNPH with Welch's t-test, receiver operating characteristic (ROC) curve analysis, and multiple logistic regression analysis. RESULTS: We found significant increased levels of glycerate and N-acetylneuraminate and significant decreased levels of serine and 2-hydroxybutyrate in the CSF of patients with AD compared to the CSF of patients with iNPH. The ROC curve analysis with these four metabolites showed that the area under the ROC curve was 0.90, indicating good discrimination between AD and iNPH. CONCLUSIONS: This study identified four metabolites that could possibly discriminate between AD and iNPH, which previous research has shown are closely related to the risk factors, pathogenesis, and symptoms of AD. Analyzing pathway-specific metabolites in the CSF of patients with AD may further elucidate the mechanism and pathogenesis of AD.

Comparison of olfactory and gustatory disorders in Alzheimer's disease.

Patients with Alzheimer's disease (AD) develop olfactory and gustatory disorders. However, the order of failure and relevance of the pathophysiology are unclear. We compared olfactory identification and whole mouth gustation in patients with AD to those with mild cognitive impairment (MCI) and to healthy controls (HC) and assessed correlations with pathophysiology. Patients with AD (n = 40), MCI (n = 34), and HC (n = 40) were recruited. We performed the Odor Stick Identification Test for Japanese (OSIT-J), gustatory test by the intraoral dropping method using taste solutions, Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale-cognitive subscale Japanese version (ADAS-J cog), Touch Panel-type Dementia Assessment Scale (TDAS), and measurement of amyloid ß (Aß) 42 and phosphorylated tau (p-tau) 181 levels in cerebrospinal fluid (CSF). Patients with AD and MCI had lower OSIT-J scores than did the HC. The OSIT-J score was correlated with the MMSE, ADAS-J cog, TDAS, and Aß42 results. There were no significant differences in the gustatory test scores among the three groups. The gustatory test score was only correlated with the MMSE, ADAS-J cog, and TDAS results. Olfactory function decreased in AD and MCI patients and was associated with CSF biomarker levels and cognitive disorders. The results suggest that olfactory function is impaired in early stage of AD. Gustatory function was not correlated with CSF biomarkers, which suggests that it may not be impaired in early stage of AD.

Cerebrospinal fluid biomarkers of Alzheimer's disease are associated with carotid plaque score and hemodynamics in intra- and extra-cranial arteries on ultrasonography.

Carotid plaque score (PS) and hemodynamic abnormalities in intra- and extra-cranial arteries are related to Alzheimer's disease (AD) progression. As these parameters are measured conveniently and non-invasively by ultrasonography, we examined their association with cerebral spinal fluid (CSF) AD biomarkers amyloid ß (Aß) and phosphorylated tau (p-tau). Carotid PS, mean flow velocity (MFV) in multiple intra- and extra-cranial arteries, CSF Aß42 and p-tau, neurocognitive function (assessed by the Mini-Mental State Examination and Alzheimer's Disease Assessment Scale-cognitive subscale, Japanese version), and blood lipids (total cholesterol, HDL cholesterol, LDL cholesterol, and triglyceride) were measured in AD patients (n = 42), mild cognitive impairment patients (n = 20), and cognitively normal controls (n = 18). The results were also compared among groups defined by PS range. After adjusting for blood lipids as covariates, Aß42 was higher in the PS = 1.1-2.0 mm group than in the higher PS groups (2.1-3.0, 3.1-5.0, 5.1-7.0, and >7.0 mm). However, subjects with very low PS (<1.1 mm) also had a low mean CSF Aß42. Alternatively, CSF p-tau181 did not differ between PS groups. In multiple regression analysis, Aß42 was not associated with MFVs; however, CSF p-tau181 showed a significant association with the MFV of the internal carotid and basilar arteries. Findings suggest that carotid plaque formation may accelerate Aß42 deposition, although it is not necessary for deposition. Hemodynamics abnormalities may cause increased CSF p-tau181. Ultrasonographic evaluation of PS and arterial hemodynamics may be a useful noninvasive method for estimating AD pathology.

PTPRQ as a potential biomarker for idiopathic normal pressure hydrocephalus.

Idiopathic normal pressure hydrocephalus (iNPH) is caused by the accumulation of cerebrospinal fluid (CSF) and is characterized by gait disturbance, urinary incontinence, and dementia. iNPH dementia is treatable by shunt operation; however, since the cognitive symptoms of iNPH are often similar to those of other dementias, including Alzheimer's disease (AD), accurate diagnosis of iNPH is difficult. To overcome this problem, the identification of novel diagnostic markers to distinguish iNPH and AD is warranted. Using comparative proteomic analysis of CSF from patients with iNPH and AD, protein tyrosine phosphatase receptor type Q (PTPRQ) was identified as a candidate biomarker protein for discriminating iNPH from AD. ELISA analysis indicated that the PTPRQ concentration in the CSF was significantly higher in patients with iNPH compared with those with AD. In addition, the PTPRQ concentration in the CSF of non­responders to shunt operation (SNRs) tended to be relatively lower compared with that in the responders. PTPRQ may be a useful biomarker for discriminating between patients with iNPH and AD, and may be a potential companion biomarker to identify SNRs among patients with iNPH. Additional large­scale analysis may aid in understanding the novel aspects of iNPH.