Association between Gray and White Matter Lesions and Its Involvement in Clinical Symptoms of Alzheimer's-Type Dementia.

BACKGROUND: Not only gray matter lesions (GMLs) but also white matter lesions (WMLs) can play important roles in the pathology of Alzheimer's disease (AD). The progression of cognitive impairment (CI) and behavioral and psychological symptoms of dementia (BPSD) might be caused by a concerted effect of both GML and WML. OBJECTIVE: This study aimed to investigate the association between GML and WML and how they are involved in the symptoms of CI and BPSD in dementia patients by means of imaging technology. METHODS: Patients in our memory clinic, who were diagnosed with AD-type dementia or amnestic mild cognitive impairment (aMCI) and had undergone both single-photon emission computed tomography (SPECT) and brain MRI, were consecutively enrolled (n = 156; 61 males and 95 females; 79.8 ± 7.4 years old). Symptoms of CI and BPSD were obtained from patients' medical records. For the analysis of GMLs and WMLs, SPECT data and MRI T1-weighted images were used, respectively. This study followed the Declaration of Helsinki, and all procedures were approved by the institutional ethics committee. RESULTS: According to a multivariate analysis, disorientation and disturbed attention demonstrated a relationship between the precuneus and WMLs in both hemispheres. Hyperactivity in BPSD showed multiple correlations between GMLs on both sides of the frontal cortex and WMLs. Patients with aMCI presented more multiple correlations between GMLs and WMLs compared with those with AD-type dementia regarding dementia symptoms including BPSD. CONCLUSION: The interaction between GMLs and WMLs may vary depending on the symptoms of CI and BPSD. Hyperactivity in BPSD may be affected by the functional relationship between GMLs and WMLs in the left and right hemispheres. The correlation between GMLs and WMLs may be changing in AD-type dementia and aMCI.

Impact of hs-CRP concentration on brain structure alterations and cognitive trajectory in Alzheimer's disease.

Introduction: Present study was to investigate hs-CRP concentration, brain structural alterations, and cognitive function in the context of AD [Subjective cognitive decline (SCD), mild cognitive impairment (MCI), and AD]. Methods: We retrospectively included 313 patients (Mean age = 76.40 years, 59 SCD, 101 MCI, 153 AD) in a cross-sectional analysis and 91 patients (Mean age = 75.83 years, 12 SCD, 43 MCI, 36 AD) in a longitudinal analysis. Multivariable linear regression was conducted to investigate the relationship between hs-CRP concentration and brain structural alterations, and cognitive function, respectively. Results: Hs-CRP was positively associated with gray matter volume in the left fusiform (ß = 0.16, pFDR = 0.023) and the left parahippocampal gyrus (ß = 0.16, pFDR = 0.029). Post hoc analysis revealed that these associations were mainly driven by patients with MCI and AD. The interaction of diagnosis and CRP was significantly associated with annual cognitive changes (ß = 0.43, p = 0.008). Among these patients with AD, lower baseline CRP was correlated with greater future cognitive decline (r = -0.41, p = 0.013). Conclusion: Our study suggests that increased hs-CRP level may exert protective effect on brain structure alterations and future cognitive changes among patients already with cognitive impairment.

Detecting Comparative Features of Comprehensive Geriatric Assessment through the International Classification of Functioning, Disability, and Health Linkage: A Web-Based Survey.

Multidimensional assessments are important in evaluating the overall health of older adults. The comprehensive geriatric assessment (CGA) is a representative framework; however, the burden associated with the CGA has led to the development of simplified multidimensional tools. Comparing these tools to the CGA can help utilize them effectively. However, a direct comparison is challenging owing to the conceptual nature of the CGA. In this study, we conducted a web-based survey to identify essential CGA components by linking International Classification of Functioning, Disability, and Health (ICF) category level 2 items and "not defined/not covered" (nd/nc) items. Healthcare professionals and individuals aged >65 years participated in a two-stage Delphi study. In total, 182 respondents (7 geriatricians, 22 nurses, 20 therapists, and 4 case managers) completed the survey. Sixty-one essential components for CGA were identified, including 55 ICF categories. Additionally, personal factors (i.e., proactiveness) and nd/nc items (i.e., subjective perceptions) were aggregated. The results suggest that the CGA includes objective conditions of intrinsic capacity, functional ability, and environment as well as subjective perceptions and proactiveness toward those conditions. Thus, CGA is not merely expected to assess geriatric syndrome but also to estimate broader concepts, such as interoception, resilience, and quality of life.

Evolutionary process toward avian-like cephalic thermoregulation system in Theropoda elucidated based on nasal structures.

It has long been discussed whether non-avian dinosaurs were physiologically closer to ectotherms or endotherms, with the internal nasal structure called the respiratory turbinate present in extant endotherms having been regarded as an important clue for this conundrum. However, the physiological function and relevance of this structure for dinosaur physiology are still controversial. Here, we found that the size of the nasal cavity relative to the head size of extant endotherms is larger than those of extant ectotherms, with that of the dromaeosaurid Velociraptor being below the extant endotherms level. The result suggests that a large nasal cavity accommodating a well-developed respiratory turbinate is primarily important as a thermoregulation apparatus for large brains characteristic of endothermic birds and mammals, and the nasal cavity of Velociraptor was apparently not large enough to carry out this role required for an endothermic-sized brain. In addition, a hypothesis that the enlargement of the nasal cavity for brain cooling has been associated with the skull modification in the theropod lineage toward modern birds is proposed herein. In particular, the reduction of the maxilla in derived avialans may have coincided with acquisition of the avian-like cephalic thermoregulation system.

Impact of atrial fibrillation on the cognitive decline in Alzheimer's disease.

BACKGROUND: Atrial fibrillation (AF) is a strong risk factor for Alzheimer's disease (AD) independent of ischemic stroke. However, the clinicopathological impact of AF on the severity of AD has not been well elucidated. We aimed to investigate the clinical differences between dementia patients with AF and those without AF by means of imaging data. METHODS: Following approval from the institutional ethics committee, patients with newly diagnosed AD or amnestic mild cognitive impairment (aMCI) were retrospectively screened (n = 170, 79.5 ± 7.4 years old). Cognitive function was assessed using the Mini-Mental State Examination (MMSE). Based on the MRI data, the cerebral volume, cerebral microbleeds (CMBs), periventricular white matter lesions (WMLs), and deep WMLs were evaluated. The regional cerebral blood flow (rCBF) was measured using 123I-IMP SPECT. RESULTS: Of the patients, 14 (8.2%) and 156 (91.8%) had AF (AF group) and sinus rhythm (SR group), respectively. The AF group had significantly lower MMSE scores than the SR group (average [standard deviation (SD)]: 19.4 [4.4] and 22.0 [4.4], respectively; p = 0.0347). Cerebral volume and CMBs did not differ between the two groups. The periventricular WMLs, but not the deep WMLs, were significantly larger in the AF group than in the SR group (mean [SD] mL: 6.85 [3.78] and 4.37 [3.21], respectively; p = 0.0070). However, there was no significant difference in rCBF in the areas related to AD pathology between the two groups. CONCLUSION: AD and aMCI patients with AF showed worse cognitive decline along with larger periventricular WMLs compared to those with SR, although the reduction of rCBF was not different between patients with AF and SR. The white matter lesions may be a more important pathology than the impairment of cerebral blood flow in dementia patients with AF. A larger study is needed to confirm our findings in the future.

A Pilot Study of Whole-Brain Low-Intensity Pulsed Ultrasound Therapy for Early Stage of Alzheimer's Disease (LIPUS-AD): A Randomized, Double-Blind, Placebo-Controlled Trial.

The prevalence of Alzheimer's disease (AD) has been rapidly increasing worldwide. We have developed a novel angiogenic therapy with low-intensity pulsed ultrasound (LIPUS), which is effective and safe in animal models of AD and vascular dementia. We performed two trials of LIPUS therapy for AD (mild cognitive impairment due to AD and mild AD); a roll-in open trial for safety, and a randomized, double-blind, placebo-controlled (RCT) trial for efficacy and safety. The LIPUS therapy was performed for whole brain through the bilateral temporal bones for one hour 3 times a week as one session under the special conditions (1.3 MPa, 32 cycles, 5% duty cycle) we identified. The LIPUS therapy was performed for one session in the roll-in trial, and 6 sessions in the RCT trial with 3-month intervals for 1.5 years. The primary endpoint was ADAS-J cog scores. The RCT trial was terminated prematurely due to the COVID-19 pandemic. In the roll-in trial (N = 5), no adverse effects were noted. In the RCT trial (N = 22), the worsening of ADAS-J cog scores tended to be suppressed in the LIPUS group compared with the placebo group at week 72 (P = 0.257). When responders were defined as those with no worsening of ADAS-J cog scores at week 72, the prevalence was 50% (5/10) and 0% (0/5) in the LIPUS and placebo groups, respectively (P = 0.053). No adverse effects were noted. These results suggest that the LIPUS therapy is safe and tends to suppress cognitive impairment although a next pivotal trial with a large number of subjects is warranted.

Impact of constipation on progression of Alzheimer's disease: A retrospective study.

BACKGROUND AND PURPOSE: In terms of the gut-brain axis, constipation has been considered to be an important factor of neurodegenerative diseases, although the exact mechanism is still controversial. Herein, we aimed to investigate the contribution of constipation to the progression of dementia in a retrospective study. METHODS: Patients of Alzheimer's disease(AD) and amnestic mild cognitive impairment were consecutively screened between January 2015 and December 2020, and those of whom brain MRI and neuropsychological tests were performed twice were enrolled in this study. Participants were classified into with constipation (Cons[+], n = 20) and without constipation (Cons[-], n = 64) groups. Laboratory data at the first visit were used. Regression analysis was performed in MMSE, ADAS-Cog, and the volumes of hippocampus on MRI-MPRAGE images and deep white matter lesions (DWMLs) on MRI-FLAIR images obtained at two different time points. RESULTS: The main finding was that the Cons[+] group showed 2.7 times faster decline in cognitive impairment compared with the Cons[-] group, that is, the liner coefficients of ADAS-Cog were 2.3544 points/year in the Cons[+] and 0.8592 points/year in the Cons[-] groups. Ancillary, changes of DWMLs showed significant correlation with the time span (p < 0.01), and the liner coefficients of DWMLs were 24.48 ml/year in the Cons[+] and 14.83 ml/year in the Cons[-] group, although annual rate of hippocampal atrophy was not different between the two groups. Moreover, serum homocysteine level at baseline was significantly higher in the Cons[+] group than Cons[-] group (14.6 ± 6.4 and 11.5 ± 4.2 nmol/ml, respectively: p = 0.03). CONCLUSION: There is a significant correlation between constipation and faster progression of AD symptoms along with expansion of DWMLs.

Perceived social isolation is correlated with brain structure and cognitive trajectory in Alzheimer's disease.

Both objective and perceived social isolations were associated with future cognitive decline and increase risk of Alzheimer's disease (AD). However, the impacts of perceived social isolation depending on different clinical stages of AD have not been elucidated. The aim of this study was to investigate the influence of perceived social isolation or loneliness on brain structure and future cognitive trajectories in patients who are living with or are at risk for AD. A total of 176 elderly patients (mean age of 78 years) who had complaint of memory problems (39 subjective cognitive decline [SCD], 53 mild cognitive impairment [MCI], 84 AD) underwent structural MRI and neuropsychological testing. Loneliness was measured by one binary item question "Do you often feel lonely?." Voxel-based morphometry was conducted to evaluate regional gray matter volume (rGMV) difference associated with loneliness in each group. To evaluate individual differences in cognitive trajectories based on loneliness, subgroup analysis was performed in 51 patients with AD (n = 23) and pre-dementia status (SCD-MCI, n = 28) using the longitudinal scores of Alzheimer's Disease Assessment Scale-cognitive component-Japanese version (ADAS-Jcog). Whole brain VBM analysis comparing lonely to non-lonely patients revealed loneliness was associated with decreased rGMV in bilateral thalamus in SCD patients and in the left middle occipital gyrus and the cerebellar vermal lobules I - V in MCI patients. Annual change of ADAS-Jcog in patients who reported loneliness was significantly greater comparing to these non-lonely in SCD-MCI group, but not in AD group. Our results indicate that perceived social isolation, or loneliness, might be a comorbid symptom of patients with SCD or MCI, which makes them more vulnerable to the neuropathology of future AD progression.

Alzheimer's Disease and Type 2 Diabetes Mellitus: The Use of MCT Oil and a Ketogenic Diet.

Recently, type 2 diabetes mellitus (T2DM) has been reported to be strongly associated with Alzheimer's disease (AD). This is partly due to insulin resistance in the brain. Insulin signaling and the number of insulin receptors may decline in the brain of T2DM patients, resulting in impaired synaptic formation, neuronal plasticity, and mitochondrial metabolism. In AD patients, hypometabolism of glucose in the brain is observed before the onset of symptoms. Amyloid-ß accumulation, a main pathology of AD, also relates to impaired insulin action and glucose metabolism, although ketone metabolism is not affected. Therefore, the shift from glucose metabolism to ketone metabolism may be a reasonable pathway for neuronal protection. To promote ketone metabolism, medium-chain triglyceride (MCT) oil and a ketogenic diet could be introduced as an alternative source of energy in the brain of AD patients.

Mapping marine debris encountered by albatrosses tracked over oceanic waters.

Anthropogenic marine debris is a threat to marine organisms. Understanding how this debris spatially distributes at sea and may become associated with marine wildlife are key steps to tackle this current issue. Using bird-borne GPS- and video-loggers on 13 black-footed albatrosses Phoebastria nigripes breeding in Torishima, Japan, we examined the distribution of large floating debris in the Kuroshio Current area, western North Pacific. A total of 16 floating debris, including styrofoam (n = 4), plastic pieces (n = 3), plastic sheet (n = 1), fishery-related items (rope or netting, n = 4), and unidentified debris (n = 4), were recorded across the 9003 km covered by nine birds. The debris was concentrated in the southern area of the Kuroshio Current, where the surface current was weak, and the albatrosses were foraging. The albatrosses displayed changes in flight direction towards the debris when at a mean distance of 4.9 km, similarly to when approaching prey, and one bird was observed pecking at a plastic sheet; indicating that albatrosses actively interacted with the debris. This paper shows the usefulness of studying wide-ranging marine predators through the use of combined biologging tools, and highlights areas with increased risk of debris exposure and behavioral responses to debris items.

Host-parasite relationships between seabirds and the haemadipsid leech Chtonobdella palmyrae (Annelida: Clitellata) inhabiting oceanic islands in the Pacific Ocean.

The duognathous haemadipsid leeches of the genus Chtonobdella show a trans-oceanic distribution throughout the Indo-Pacific region. Although passive long-distance dispersal (LDD) of Chtonobdella leeches by birds has been suggested, little is known about the host-parasite relationships between avian hosts and Chtonobdella leeches. In the current study, we investigated Chtonobdella leech infestations of the eyes and other mucus membranes of migratory procellariiform seabirds, Pterodroma hypoleuca and Oceanodroma tristrami, captured at six locations in the Bonin Islands, Honshu and Okinawa Island, Japan. Analyses of the partial sequences of 18S rRNA, 28S rRNA, and mitochondrial cytochrome c oxidase subunit I (COI) and morphological examination of the specimens demonstrated that the Chtonobdella leeches belonged to Chtonobdella palmyrae, which is indigenous to Palmyra Atoll in the Northern Line Islands. A dominant COI sequence type was observed in samples from all six sites; therefore, C. palmyrae almost surely dispersed approximately 1000 km by infesting the eyes and mucus membranes of procellariiform seabirds. The host-parasite relationships between procellariiform seabirds and C. palmyrae provide explicit evidence of the LDD of duognathous haemadipsid leeches. The taxonomic status of Haemadipsa zeylanica ivosimae from the Volcano Islands is also briefly discussed.

Kampo Medicine for Various Aging-Related Symptoms: A Review of Geriatric Syndrome.

With the continued growth of the aging population in Japan, geriatric syndrome (GS), which is associated with aging-related symptoms, has become a social problem. GS is caused by physiological and pathological aging and may manifest various symptoms. Physicians use multidisciplinary approaches to provide treatment for individual GS symptoms. Kampo medicine, a Japanese traditional medicine that uses multiple pharmacologically active substances, is useful for many syndromes, conditions, disorders, and diseases associated with GS. Evidence of the effectiveness of Kampo medicine for GS has accumulated in recent years. The effects of Kampo treatment for symptoms related to functional decline of the cardiovascular, respiratory, and digestive systems, cognitive impairment and related disorders, pain and other sensory issues, among others, support the use of Kampo medicine for the management of GS. The role of Kampo medicine for GS is summarized in this review.

YAP-dependent necrosis occurs in early stages of Alzheimer's disease and regulates mouse model pathology.

The timing and characteristics of neuronal death in Alzheimer's disease (AD) remain largely unknown. Here we examine AD mouse models with an original marker, myristoylated alanine-rich C-kinase substrate phosphorylated at serine 46 (pSer46-MARCKS), and reveal an increase of neuronal necrosis during pre-symptomatic phase and a subsequent decrease during symptomatic phase. Postmortem brains of mild cognitive impairment (MCI) rather than symptomatic AD patients reveal a remarkable increase of necrosis. In vivo imaging reveals instability of endoplasmic reticulum (ER) in mouse AD models and genome-edited human AD iPS cell-derived neurons. The level of nuclear Yes-associated protein (YAP) is remarkably decreased in such neurons under AD pathology due to the sequestration into cytoplasmic amyloid beta (Aß) aggregates, supporting the feature of YAP-dependent necrosis. Suppression of early-stage neuronal death by AAV-YAPdeltaC reduces the later-stage extracellular Aß burden and cognitive impairment, suggesting that preclinical/prodromal YAP-dependent neuronal necrosis represents a target for AD therapeutics.

Transcatheter aortic valve implantation and cognitive function in elderly patients with severe aortic stenosis.

AIMS: The aim of this study was to examine the mechanisms of cognitive impairment and reversibility in elderly patients with severe aortic stenosis (AS) after transcatheter aortic valve implantation (TAVI) with special reference to cerebral blood flow (CBF). METHODS AND RESULTS: We examined 15 elderly patients with severe AS (mean age 83.2±4.5 years, 12 female) who underwent TAVI. Before and three months after TAVI, we evaluated cognitive function with the Logical Memory II test (LM II), cardiac output (CO) with echocardiography, and CBF with 99mTc single-photon emission computed tomography (SPECT). LM II score and CO were significantly increased after TAVI compared with baseline (p<0.01 for LM II, p<0.005 for CO). Notably, CBF in the local regions, including that in the right hippocampus, was significantly increased after TAVI (p<0.005 at each voxel). The patients with increased CO after TAVI also showed significantly increased CBF in the right hippocampus compared with those without it (p<0.01). Importantly, CBF in the right hippocampus was positively correlated with LM II scores (p<0.05). CONCLUSIONS: These results provide the first evidence that TAVI may improve cognitive functions associated with increased cerebral perfusion especially in the hippocampus in elderly patients with severe AS.

Risk factors for adverse drug reactions in older inpatients of geriatric wards at admission: Multicenter study.

AIM: To investigate the characteristics of adverse drug reactions (ADR) and their risk factors among very old patients in five geriatric wards in Japan. METHODS: A retrospective observational multicenter study was carried out to investigate factors related to ADR in older inpatients from geriatric wards of five university hospitals in Japan. Data including drugs profile and short-form comprehensive geriatric assessment were obtained from medical charts. ADR were identified from geriatrician's reports. For each ADR, symptoms and causal drugs were clarified, and factors associated with ADR were analyzed statistically. RESULTS: In 1155 patients (52.5% women, mean age 82.8 ± 7.0 years), the proportion with ADR was 15.4%. There was a great variety of signs and symptoms of ADR, and a great variety of drugs suspected to be the cause of ADR. On multiple logistic regression analysis, ADR was significantly associated with an increase in drugs (odds ratio 1.11, 95% CI 1.07-1.16) and emergency admission (odds ratio 2.76, 95% CI 1.82-4.15). Receiver operating characteristic curve analysis showed that the optimal cut-off number of drugs for predicting ADR was ≥7. CONCLUSIONS: In geriatric inpatients, polypharmacy (especially ≥7 drugs) and emergency admission were associated with ADR. Because there was a great variety of ADR in the study, clinicians must consider reviewing all drugs to prevent adverse drugs reactions during admission in this vulnerable population. Geriatr Gerontol Int 2019; ••: ••-••. Geriatr Gerontol Int 2020; 20: 144-149.

Development of geriatric syndromes after taking countermeasures for polypharmacy: an overlooked issue of quitting semiregular single-dose medicine.

We report a case of an elderly woman on polypharmacy who developed appetite loss, general fatigue and muscle weakness mainly from secondary adrenal insufficiency caused by quitting one semiregular single-dose medicine. Because the degree of insufficiency was mild, her symptoms were eliminated after some time without additional treatment. The present case includes important lessons related to medication management in elderly patients. Additionally, the present case also warns us to be cautious while diagnosing geriatric syndromes as a part of the physiological aging process or additional disease symptoms. Drug-induced geriatric syndrome from quitting semiregular-use drugs should be investigated in future studies.

Lower Serum Calcium as a Potentially Associated Factor for Conversion of Mild Cognitive Impairment to Early Alzheimer's Disease in the Japanese Alzheimer's Disease Neuroimaging Initiative.

BACKGROUND: Effect of serum calcium level to the incidence of mild cognitive impairment (MCI) conversion to early Alzheimer's disease (AD) remains uncertain. OBJECTIVE: To investigate association between baseline serum calcium and the MCI conversion in the Japanese Alzheimer's Disease Neuroimaging Initiative (J-ADNI) study cohort. METHODS: In this sub-analysis of J-ADNI study, we reviewed data from MCI participants at baseline regarding their conversion to early AD during the 3 years of observation period and assessed the associated factors including serum calcium level. In addition, we compared our results from the J-ADNI study with the corresponding results from the North American (NA)-ADNI. RESULTS: Of 234 eligible MCI participants from the J-ADNI cohort, 121 (51.7%) converted to AD during the first 36 months of observation. Using univariate analysis, being female, having shorter years of education, and lower serum calcium level were correlated with increased risk of MCI-to-AD conversion exclusively in J-ADNI cohort. The lower corrected serum calcium level remained as one of conversion-associated factors in the J-ADNI cohort even after adjustment for multiple confounding variables, although this was not observed in the NA-ADNI cohort. CONCLUSION: Our findings suggest that lower serum calcium may be associated with an increased risk of MCI conversion to AD in Japanese cohorts. The reason for this correlation remains unclear and further external validation using other Asian cohorts is needed. It would be interesting for future AD studies to obtain serum calcium levels and other related factors, such as vitamin D levels, culture-specific dietary or medication information.

Could problem lists summarize comprehensive geriatric assessments? A nationwide cross-sectional survey on geriatricians' attitudes towards problem lists.

AIM: The use of problem lists is encouraged to overcome the inconsistency in reporting comprehensive geriatric assessment results. The present study aimed to identify the latent variables influencing the use of geriatrician problem lists. METHODS: Surveys were sent to all geriatricians registered with the Japan Geriatrics Society (n = 1439) as of November 2015, and responses (n = 204) were analyzed with univariate and exploratory factor analyses. To account for active, inactive and tentative items, the survey addressed "disease," "symptom" and "condition" separately. RESULTS: Most geriatricians (34.8%) composed problem lists for interdisciplinary information sharing. Nearly half of the respondents (46.6%) created problem lists for every patient. Information omissions were mainly due to the exclusion of information from other specialties (26% for omitted diseases and 12.3% for omitted symptoms), lack of time (25.5% for omitted diseases, 22.1% for omitted symptoms and 26.5% for omitted conditions), and lack of standardization of terminologies regarding observed diseases, symptoms and conditions (12.3% for omitted diseases, 19.6% for omitted symptoms and 16.7% for omitted conditions). An exploratory factor analysis, based on 20 predefined symptoms and conditions that are frequently omitted from problem lists, showed that considering the symptom "geriatric syndromes" and the condition "assistance needs in medication management" are crucial for improving problem list comprehensiveness. CONCLUSIONS: Geriatricians commonly use problem lists; however, there is considerable variation regarding the problems listed and their relationships. The listings of "geriatric syndrome" and "assistance needs in medication management" are crucial for improving problem list comprehensiveness. Geriatr Gerontol Int 2019; 19: 159-164.

Neuroimaging-pathological correlations of [18F]THK5351 PET in progressive supranuclear palsy.

Recent positron emission tomography (PET) studies have demonstrated the accumulation of tau PET tracer in the affected region of progressive supranuclear palsy (PSP) cases. To confirm the binding target of radiotracer in PSP, we performed an imaging-pathology correlation study in two autopsy-confirmed PSP patients who underwent [18F]THK5351 PET before death. One patient with PSP Richardson syndrome showed elevated tracer retention in the globus pallidus and midbrain. In a patient with PSP-progressive nonfluent aphasia, [18F]THK5351 retention also was observed in the cortical areas, particularly the temporal cortex. Neuropathological examination confirmed PSP in both patients. Regional [18F]THK5351 standardized uptake value ratio (SUVR) in antemortem PET was significantly correlated with monoamine oxidase-B (MAO-B) level, reactive astrocytes density, and tau pathology at postmortem examination. In in vitro autoradiography, specific THK5351 binding was detected in the area of antemortem [18F]THK5351 retention, and binding was blocked completely by a reversible selective MAO-B inhibitor, lazabemide, in brain samples from these patients. In conclusion, [18F]THK5351 PET signals reflect MAO-B expressing reactive astrocytes, which may be associated with tau accumulation in PSP.