Clinicopathological study of dementia with grains presenting with parkinsonism compared with a typical case.

Argyrophilic grain disease (AGD) is one of the major pathological backgrounds of senile dementia. Dementia with grains refers to cases of dementia for which AGD is the sole background pathology responsible for dementia. Recent studies have suggested an association between dementia with grains and parkinsonism. In this study, we aimed to present two autopsy cases of dementia with grains. Case 1 was an 85-year-old man who exhibited amnestic dementia and parkinsonism, including postural instability, upward gaze palsy, and neck and trunk rigidity. The patient was clinically diagnosed with progressive supranuclear palsy and Alzheimer's disease. Case 2 was a 90-year-old man with pure amnestic dementia, clinically diagnosed as Alzheimer's disease. Recently, we used cryo-electron microscopy to confirm that the tau accumulated in both cases had the same three-dimensional structure. In this study, we compared the detailed clinical picture and neuropathological findings using classical staining and immunostaining methods. Both cases exhibited argyrophilic grains and tau-immunoreactive structures in the brainstem and basal ganglia, especially in the nigrostriatal and limbic systems. However, Case 1 had more tau immunoreactive structures. Considering the absence of other disease-specific structures such as tufted astrocytes, astrocytic plaques and globular glial inclusions, lack of conspicuous cerebrovascular disease, and no history of medications that could cause parkinsonism, our findings suggest an association between AGD in the nigrostriatal system and parkinsonism.

Correlations between cerebrospinal fluid homovanillic acid and dopamine transporter SPECT in degenerative parkinsonian syndromes.

Both cerebrospinal fluid (CSF) homovanillic acid (HVA) and striatal dopamine transporter (DAT) binding on single-photon emission computed tomography (SPECT) reflect nigrostriatal dopaminergic function, but studies on the relationship between the two have been limited. It is also unknown whether the reported variance in striatal DAT binding among diseases reflects the pathophysiology or characteristics of the subjects. We included 70 patients with Parkinson's disease (PD), 12 with progressive supranuclear palsy (PSP), 12 with multiple system atrophy, six with corticobasal syndrome, and nine with Alzheimer's disease as disease control, who underwent both CSF analysis and 123I-N-ω-fluoropropyl-2ß-carbomethoxy-3ß-(4-iodophenyl)nortropane (123I-ioflupane) SPECT. We evaluated the correlation between CSF HVA concentration and the specific binding ratio (SBR) of striatal DAT binding. We also compared the SBR for each diagnosis, controlling for CSF HVA concentration. The correlations between the two were significant in patients with PD (r = 0.34, p = 0.004) and PSP (r = 0.77, p = 0.004). The mean SBR value was the lowest in patients with PSP and was significantly lower in patients with PSP than in those with PD (p = 0.037) after adjusting for CSF HVA concentration. Our study demonstrates that striatal DAT binding correlates with CSF HVA concentration in both PD and PSP, and striatal DAT reduction would be more advanced in PSP than in PD at an equivalent dopamine level. Striatal DAT binding may correlate with dopamine levels in the brain. The pathophysiology of each diagnosis may explain this difference.

A diagnostic strategy for Parkinsonian syndromes using quantitative indices of DAT SPECT and MIBG scintigraphy: an investigation using the classification and regression tree analysis.

PURPOSE: We aimed to evaluate the diagnostic performances of quantitative indices obtained from dopamine transporter (DAT) single-photon emission computed tomography (SPECT) and 123I-metaiodobenzylguanidine (MIBG) scintigraphy for Parkinsonian syndromes (PS) using the classification and regression tree (CART) analysis. METHODS: We retrospectively enrolled 216 patients with or without PS, including 80 without PS (NPS) and 136 with PS [90 Parkinson's disease (PD), 21 dementia with Lewy bodies (DLB), 16 progressive supranuclear palsy (PSP), and 9 multiple system atrophy (MSA). The striatal binding ratio (SBR), putamen-to-caudate ratio (PCR), and asymmetry index (AI) were calculated using DAT SPECT. The heart-to-mediastinum uptake ratio (H/M) based on the early (H/M [Early]) and delayed (H/M [Delay]) images and cardiac washout rate (WR) were calculated from MIBG scintigraphy. The CART analysis was used to establish a diagnostic decision tree model for differentiating PS based on these quantitative indices. RESULTS: The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 87.5, 96.3, 93.3, 92.9, and 93.1 for NPS; 91.1, 78.6, 75.2, 92.5, and 83.8 for PD; 57.1, 95.9, 60.0, 95.4, and 92.1 for DLB; and 50.0, 98.0, 66.7, 96.1, and 94.4 for PSP, respectively. The PCR, WR, H/M (Delay), and SBR indices played important roles in the optimal decision tree model, and their feature importance was 0.61, 0.22, 0.11, and 0.05, respectively. CONCLUSION: The quantitative indices showed high diagnostic performances in differentiating NPS, PD, DLB, and PSP, but not MSA. Our findings provide useful guidance on how to apply these quantitative indices in clinical practice.

[123I]-IMP single-photon emission computed tomography imaging in visual snow syndrome: A case series.

BACKGROUND: Visual snow syndrome (VSS) is a neurological condition characterized by persistent flickering dots in the visual fields, palinopsia, enhanced entoptic phenomenon, photophobia, and nyctalopia. Neuroimaging evidence supports the role of the visual association cortex in visual snow syndrome.Case series: We provided clinical care to three patients with visual snow syndrome, in whom [123I]-IMP single-photon emission computed tomography (SPECT) imaging was performed. Case 1 was a 21-year-old male with a past history of migraine with aura who exhibited visual snow and entoptic phenomenon. In this patient, [123I]-IMP SPECT imaging revealed right occipital and temporal hypoperfusion with a distribution matching the ventral visual stream. [123I]-IMP SPECT imaging detected only mild bilateral frontal hypoperfusion in Case 2 and no overt abnormalities in Case 3. CONCLUSION: Although visual snow syndrome seems to be a heterogenous condition, our observations indicate that abnormal visual processing within the ventral visual stream may play a role in the pathogenesis of this condition.

Can we predict amyloid deposition by objective cognition and regional cerebral blood flow in patients with subjective cognitive decline?

BACKGROUND: Subjective cognitive decline (SCD) may herald the first symptoms of Alzheimer's disease (AD) whereas individuals with beta-amyloid (Aß) deposition are regarded as a high-risk group for AD. Recently, amyloid positron emission tomography (PET) studies have demonstrated clinical and cognitive feature differences between Aß-positive and negative SCD, but details of their differences remain unclear. We aimed to investigate the relationships among Aß deposition, clinical, and cognitive features in patients with SCD. METHODS: Forty-two patients with SCD (22 women, 74.5 ± 4.7 years) were examined using fluorine-18 florbetaben PET and were divided into Aß-positive (n = 10) and negative (n = 32) groups. We compared cognitive and psychological outcomes, and single photon emission computed tomography (SPECT) imaging data between the two groups. In addition, a linear regression analysis was performed to assess relationships between the severity of SCD and neuropsychological tests, affective scores, and demographic factors. RESULTS: The rate of score changes from the immediate recall to delayed recall in the logical memory subtest of the Wechsler's Memory Scale Revised were different between the groups (P = 0.04). However, the binary logistic regression analysis showed no significant differences between the two. In addition, the severity of SCD was significantly strong in women (P = 0.002). Furthermore, within the Aß-negative group, subjective memory loss correlated with word fluency category score (P = 0.023) and apathy scale (P = 0.037). CONCLUSIONS: No significant differences were observed between Aß-positive and -negative SCD on any of the neuropsychological measures, clinical measures, or SPECT imaging. Further, the severity of SCD was not predicted by the symptoms of anxiety, depression, or neuropsychological examination.

Steady-state relationship between average glucose, HbA1c and RBC lifespan.

HbA1c is used to estimate average glucose. Previous studies showed linear relationship between average glucose and HbA1c. We made a new theoretical relationship using recently proposed Γ-like function model of erythrocyte lifespan. We showed the relationship between average glucose and HbA1c; we approximated it into a simple hyperbolic function: HbA1c=MRBCkgAG/(1+(2/3)MRBCkgAG), whose inverse function is easily obtained. Apparent linear relationship is an approximation of the curved relationship. Hyperbolic function would provide a more accurate approximation than a linear equation. Physicians should keep in mind the curved relationship and be aware that extremely high HbA1c indicates acceleratingly high glucose level.

The psychological impact of disclosing amyloid status to Japanese elderly: a preliminary study on asymptomatic patients with subjective cognitive decline.

ABSTRACTIn Japan, 4.6 million people are living with dementia and the number is expected to rise to 7 million by 2025. Amyloid-ß (Aß) positron emission tomography (PET) is used for cognitively normal Japanese people with or without subjective cognitive decline (SCD) for the purpose of clinical trials or diagnosis. Nevertheless, no empirical studies have been conducted on the safety of disclosing amyloid status to such populations. We conducted amyloid PET imaging on 42 participants (Aß positive (n = 10) and negative (n = 32)). State anxiety and depression were measured at pre- and post-disclosure, and test-related distress at post-disclosure. Mean state anxiety and depression scores were below the cut-off through pre- and post-disclosure in the Aß positive and negative groups. State anxiety and depression did not change over time and were not different between groups. Mean test-related distress scores were within normal limits at post-disclosure in both groups. No significant difference was found between groups. Disclosing Aß positive results did not cause greater mood disturbance than negative results in a short period of time. The short-term psychological safety of disclosing Aß PET results to asymptomatic Japanese adults with SCD was indicated.

Dinosaur Tail Sign: A Useful Spinal MRI Finding Indicative of Cerebrospinal Fluid Leakage.

OBJECTIVE: To evaluate the imaging characteristics and diagnostic utility of the "Dinosaur tail sign" in the diagnosis of cerebrospinal fluid (CSF) leakage. BACKGROUND: The authors propose the "Dinosaur tail sign," defined as a combination of the dorsal epidural hyperintensities, fat tissue, spinal cord, and cauda equine on lumbosacral sagittal fat-suppressed T2-weighted image (FST2WI), as a sensitive indicator for diagnosing CSF leakage. METHODS: Imaging characteristics of the "Dinosaur tail sign" was evaluated in seven spontaneous intracranial hypotension (SIH) and 23 iatrogenic CSF leakage (ICSFL) patients. Additionally, the diagnostic index was compared between the "Dinosaur tail sign" and other previously reported useful magnetic resonance imaging (MRI) and magnetic resonance myelography (MRM) findings. RESULTS: In contrast to other imaging findings including the epidural expansion, floating dural sac sign, and distension of the spinal epidural veins on MRI, and paraspinal fluid collections (PFC) on MRM, the "Dinosaur tail sign" was found equally in both SIH and ICSFL patients (6 SIH and 19 ICSFL; 83% of all patients with CSF leakage). The "Dinosaur tail sign" showed sufficient diagnostic utility (sensitivity 83%, specificity 94%, accuracy 89%) that was comparable to that of PFC. CONCLUSION: The "Dinosaur tail sign" is a useful imaging finding suggestive of CSF leakage. Evaluation of subtle interspinous arched hyperintensities on spinal MRI is mandatory for the diagnosis of SIH and ICSFL.

Extremely Low Prevalence of Amyloid Positron Emission Tomography Positivity in Parkinson's Disease without Dementia.

BACKGROUND: Most cases of dementia with Lewy bodies (DLB) show Alzheimer's disease pathology-like senile plaques and neurofibrillary tangles. Several studies have also revealed a high prevalence of positive amyloid imaging with positron emission tomography (PET) in DLB and moderate prevalence in Parkinson's disease (PD) with dementia. However, it remains unclear in PD without dementia as to when the brain ß amyloid (Aß) burden begins and progresses. Our study aimed to determine the prevalence of Aß deposition in PD without dementia using amyloid PET. METHODS: This was a cross-sectional study on 33 patients with PD without dementia, of whom 21 had normal cognition and 12 met the criteria for PD-mild cognitive impairment. All subjects underwent neuropsychological assessment and [18F] florbetaben (FBB) PET. RESULTS: All subjects had Lewy body-related disorders, displaying a significantly reduced myocardial [123I] metaiodobenzylguanidine uptake. The cortical FBB-binding pattern in all subjects, including APOE e4 carriers, suggested negative Aß deposition. CONCLUSION: Patients with PD without dementia exhibit an extremely low prevalence of Aß positivity compared with those reported in cognitively normal elderly controls. Further longitudinal imaging studies and long-term follow-up are needed; however, our findings provide novel insights for understanding Aß metabolism in PD.

Applications of artificial intelligence in dementia.

The recent evolution of artificial intelligence (AI) can be considered life-changing. In particular, there is great interest in emerging hot topics in AI such as image classification and natural language processing. Our world has been revolutionized by convolutional neural networks and transformer for image classification and natural language processing, respectively. Moreover, these techniques can be used in the field of dementia. We introduce some applications of AI systems for treating and diagnosing dementia, including image-classification AI for recognizing facial features associated with dementia, image-classification AI for classifying leukoaraiosis in MRI images, object-detection AI for detecting microbleeding in MRI images, object-detection AI for support care, natural language-processing AI for detecting dementia within conversations, and natural language-processing AI for chatbots. Such AI technologies can significantly transform the future of dementia diagnosis and treatment. Geriatr Gerontol Int 2024; 24: 25-30.

18F-THK5351 Uptake May Not Estimate Neurofibrillary Tangles in In Vivo Images: A Comparison With 18F-MK-6240 Uptake.

ABSTRACT: Currently, monoamine oxidase B is recognized as the primary target of 18F-THK5351, although 18F-THK5351 was initially developed to target neurofibrillary tangles (NFTs) in Alzheimer disease. When clinically applying 18F-THK5351 PET to visualize ongoing astrogliosis via estimating monoamine oxidase B levels, a crucial concern is how much degree 18F-THK5351 uptake reflects NFTs in in vivo images. To unravel this concern, a head-to-head comparison between 18F-THK5351 and 18F-MK-6240 (estimating NFT) images in the NFT lesion ideally without accompanying astrogliosis is essential. Here, we present such a case suggesting that 18F-THK5351 uptake may not estimate NFTs in in vivo images.

α-synuclein seed amplification assay sensitivity may be associated with cardiac MIBG abnormality among patients with Lewy body disease.

Although α-synuclein seed amplification assays (α-syn SAA) are promising, its sensitivity may be affected by heterogeneity among patients with Lewy body disease (LBD). We evaluated whether α-syn SAA sensitivity is affected by patient heterogeneity, using 123I-meta-iodobenzylguanidine (MIBG) cardiac scintigraphy in early drug-naïve patients. Thirty-four patients with clinically established or probable Parkinson's disease (PD) and seven with dementia with Lewy bodies (DLB) or prodromal DLB were included. While 85.2% of patients with abnormal cardiac MIBG were α-syn SAA positive, only 14.3% were positive among those with normal scans. Logistic regression analysis showed that MIBG positivity was the only significant variable associated with α-syn SAA positivity (odds ratio 74.2 [95% confidence interval 6.1-909]). Although α-syn SAA is sensitive for LBD in patients with abnormal MIBG, the sensitivity may be lower in those with normal MIBG. Further studies are necessary to evaluate the association between patient heterogeneity and α-syn SAA sensitivity.

Associations of cerebrospinal fluid monoamine metabolites with striatal dopamine transporter binding and 123I-meta-iodobenzylguanidine cardiac scintigraphy in Parkinson's disease: Multivariate analyses.

Cerebrospinal fluid (CSF) homovanillic acid (HVA) and 5-hydroxyindole acetic acid (5-HIAA), dopamine and serotonin metabolites, are decreased in Parkinson's disease (PD). Although some reported associations between HVA and striatal dopamine transporter (DAT) or 5-HIAA and cardiac 123I-meta-iodobenzylguanidine (MIBG) findings, respectively, whether these are direct associations remained unknown. We retrospectively reviewed 57 drug-naïve patients with PD who underwent CSF analyses and DAT and cardiac MIBG imaging. Z-score of striatal DAT specific binding ratio (Z-SBR) was measured, and the positivity of MIBG abnormalities were judged by an expert. The mean age was 75.5 ± 8.7 years. Thirty-three were MIBG-positive and 24 were MIBG-negative. 5-HIAA levels were significantly lower in the MIBG-positive group. Logistic regression analysis showed that MIBG positivity was associated with 5-HIAA level (odds ratio = 0.751, p = 0.006) but not with age, sex, and HVA. DAT Z-SBR correlated with both HVA and 5-HIAA. Multiple regression analysis showed that HVA was the only significant variable associated with Z-SBR (t = 3.510, p < 0.001). We confirmed direct associations between 5-HIAA and cardiac MIBG, and between HVA and striatal DAT binding.

Diagnostic performance of the cingulate island sign ratio for differentiating dementia with Lewy bodies from Alzheimer's disease changes depending on the mini-mental state examination score.

BACKGROUND: The cingulate island sign (CIS) ratio is a diagnostic adjunct for differentiating dementia with Lewy bodies (DLB) from Alzheimer's disease (AD). A recent study showed that the CIS ratio in DLB changed depending on the Mini-Mental State Examination (MMSE) score. We aimed to evaluate whether the diagnostic performance (sensitivity and specificity) of the CIS ratio for differentiating DLB from AD changes depending on the MMSE score. METHODS: Twenty-two patients with DLB and 26 amyloid-positive patients with AD, who underwent 18F-FDG PET and completed an MMSE examination, were classified into three groups according to MMSE scores: Group A (MMSE >24), Group B (20 ≤ MMSE ≤24), and Group C (MMSE <20). In each group, we compared the CIS ratio between patients with DLB and AD and conducted receiver operating characteristic (ROC) curve analysis to calculate the sensitivity and specificity. RESULTS: Within Group B, the CIS ratio in DLB was significantly higher than that in AD (p = 0.0005), but not within Groups A (p = 0.5117) and C (p = 0.8671). ROC curve analyses showed that the sensitivities and specificities of the CIS ratio for differentiating DLB from AD were 66.7% and 77.8% in Group A, 91.7% and 100.0% in Group B, and 75.0% and 66.7% in Group C, respectively. CONCLUSIONS: The present study suggests that the diagnostic performance of the CIS ratio for differentiating DLB from AD changes depending on the MMSE score, with higher sensitivity and specificity at MMSE scores of 20-24.

High sensitivity of asymmetric 18F-THK5351 PET abnormality in patients with corticobasal syndrome.

Corticobasal syndrome (CBS) is characterized by symptoms related to the asymmetric involvement of the cerebral cortex and basal ganglia. However, early detection of asymmetric imaging abnormalities can be challenging. Previous studies reported asymmetric 18F-THK5351 PET abnormalities in CBS patients, but the sensitivity for detecting such abnormalities in larger patient samples, including early-stage cases, remains unclear. Patients clinically diagnosed with CBS were recruited. All patients displayed asymmetric symptoms in the cerebral cortex and basal ganglia. Asymmetric THK5351 PET abnormalities were determined through visual assessment. Brain MRI, perfusion SPECT, and dopamine transporter (DAT) SPECT results were retrospectively reviewed. The 15 patients had a median age of 72 years (59-86 years) and a disease duration of 2 years (0.5-7 years). Four patients met the probable and 11 met the possible CBS criteria according to Armstrong criteria at the time of PET examination. All patients, including early-stage cases, exhibited asymmetric tracer uptake contralateral to their symptom-dominant side in the cerebral cortex/subcortical white matter and striatum (100%). The sensitivity for detecting asymmetric imaging abnormalities contralateral to the symptom-dominant side was 86.7% for brain MRI, 81.8% for perfusion SPECT, and 90% for DAT SPECT. White matter volume reduction was observed in the subcortical region of the precentral gyrus with increased THK5351 uptake, occurring significantly more frequently than gray matter volume reduction. THK5351 PET may be a sensitive imaging technique for detecting asymmetric CBS pathologies, including those in early stages.

Validity of the γ-Ray Evaluation with iodoamphetamine for Cerebral Blood Flow Assessment (REICA) method for quantification of cerebral blood flow including acetazolamide challenge test.

OBJECTIVE: The γ-Ray Evaluation with iodoamphetamine for Cerebral Blood Flow Assessment (REICA) is a new method for quantifying cerebral blood flow (CBF) using single-photon emission computed tomography (SPECT) and [123I]N-isopropyl-p-iodoamphetamine (123I-IMP). The present study aimed to validate the REICA method using data including acetazolamide challenge test. METHODS: The REICA and Graph-Plot (GP) methods were used to calculate mean CBF (mCBF) for 92 acquisitions (rest: 57, stress: 35) and cerebrovascular reactivity (CVR) in 33 patients. To obtain stress data, 15 mg/kg of acetazolamide was injected intravenously 10 min before the administration of 123I-IMP, and blood samples were collected under the same conditions as rest data. The reference standard was the Autoradiograph (ARG) method using arterial blood sampling, and the accuracy of the REICA method was analyzed by comparing it with each method. RESULTS: For mCBF, the correlation coefficients (r) were 0.792 for the REICA method and 0.636 for the GP method. For CVR, r values were 0.660 for the REICA method and 0.578 for the GP method. In both acquisitions, the REICA method had a stronger correlation with the ARG method than the GP method. For mCBF, there was a significant difference in the correlation coefficient between the two correlation coefficients (p < 0.01). CONCLUSIONS: The REICA method was more accurate than the GP method in quantifying CBF and closer to the ARG method. The REICA method, which is a noninvasive method of cerebral blood flow quantification using 123I-IMP, has great medical usefulness.

Measurement of erythrocyte creatine might be useful for diagnosing latent hemolysis.

OBJECTIVES: Whereas HbA1c values are low relative to glycemia in patients with hemolytic anemia, including compensatory anemia, low HbA1c levels along with negative results for conventional hemolysis indicators have been reported in patients with latent hemolysis. Conversely, glycated albumin (GA) is a glycemic control indicator unaffected by hemolysis. Erythrocyte creatine (EC) is a hemolysis indicator that reflects the mean age of red blood cells (MRBC). We recently reported a formula for obtaining MRBC based on EC. The present study examined the usefulness of EC measurements and MRBC calculated with EC for diagnosing latent hemolysis. MATERIALS AND METHODS: Two patients with latent hemolysis and low HbA1c values relative to glycemia were investigated, while controls comprised 214 patients (including patients with hemolysis and/or type 2 diabetes mellitus). HbA1c was expressed in International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) units (iA1c). GA/iA1c ratios, reticulocyte counts, EC, and MRBC in patients with latent hemolysis were compared to non-hemolysis, compensatory hemolysis, and hemolytic anemia patients. RESULTS: Both reticulocyte counts and haptoglobin levels were within reference ranges in patients with latent hemolysis. GA/iA1c ratios and EC were higher than reference values in patients with latent hemolysis, and MRBC values were 41.6 and 48.4 days, respectively, shorter than the reference range (49.1-66.8 days). CONCLUSIONS: EC measurement and MRBC values calculated on the basis of EC might be useful for diagnosing latent hemolysis.

Decreased imaging time of amyloid PET using [18F]florbetapir can maintain quantitative accuracy.

Shortening the amount of time required to acquire amyloid positron emission tomography (PET) brain images while maintaining the accuracy of quantitative evaluation would help to overcome motion artifacts associated with Alzheimer's disease patients. The present study aimed to validate the quantitative accuracy of [18F]florbetapir ([18F]FBP) imaging over a shorter acquisition duration. Forty participants were injected with [18F]FBP, and PET images were acquired for 50-55, 50-60, and 50-70 min after injection. Three physicians visually assessed the reprocessed [18F]FBP images using a binary scale to classify them as amyloid ß (Aß) negative or positive. A mean composite standard uptake value ratio (cSUVR) > 1.075 was defined as Aß-positive based on receiver operating characteristic curves. Inter-reader and inter-acquisition duration agreements with visual assessment were evaluated using Cohen's kappa (κ). Binary visual discrimination of 102 for the 120 [18F]FBP images, was consistent among the three readers. Sixteen, sixteen, and fourteen of the 40 [18F]FBP images acquired for 50-55, 50-60, and 50-70 min after injection, respectively, were deemed Aß-positive by visual assessment. The inter-rater agreement was high, and the inter-acquisition duration agreement was almost perfect. The cSUVR did not change significantly among the acquisition durations, and the acquisition duration did not affect the outcome of discrimination based on the cSUVR cutoff. A shorter acquisition duration changed the visual assessment outcomes. Stable quantitative values were derived from [18F]FBP images acquired within 5 min. cSUVR helped to improve the performance and confidence in the outcomes of visual assessment.