Erratum: A Patient With Fahr's Disease Who Presented Prominent Visuospatial Dysfunction.

[This corrects the article on p. 117 in vol. 22, PMID: 37545866.].

Relationship between disproportionately enlarged subarachnoid-space hydrocephalus and white matter tract integrity in normal pressure hydrocephalus.

Normal pressure hydrocephalus (NPH) patients had altered white matter tract integrities on diffusion tensor imaging (DTI). Previous studies suggested disproportionately enlarged subarachnoid space hydrocephalus (DESH) as a prognostic sign of NPH. We examined DTI indices in NPH subgroups by DESH severity and clinical symptoms. This retrospective case-control study included 33 NPH patients and 33 age-, sex-, and education-matched controls. The NPH grading scales (0-12) were used to rate neurological symptoms. Patients with NPH were categorized into two subgroups, high-DESH and low-DESH groups, by the average value of the DESH scale. DTI indices, including fractional anisotropy, were compared across 14 regions of interest (ROIs). The high-DESH group had increased axial diffusivity in the lateral side of corona radiata (1.43 ± 0.25 vs. 1.72 ± 0.25, p = 0.04), and showed decreased fractional anisotropy and increased mean, and radial diffusivity in the anterior and lateral sides of corona radiata and the periventricular white matter surrounding the anterior horn of lateral ventricle. In patients with a high NPH grading scale, fractional anisotropy in the white matter surrounding the anterior horn of the lateral ventricle was significantly reduced (0.36 ± 0.08 vs. 0.26 ± 0.06, p = 0.03). These data show that DESH may be a biomarker for DTI-detected microstructural alterations and clinical symptom severity.

Magnetic resonance image-based brain age as a discriminator of dementia conversion in patients with amyloid-negative amnestic mild cognitive impairment.

Patients with amyloid-negative amnestic mild cognitive impairment (MCI) have a conversion rate of approximately 10% to dementia within 2 years. We aimed to investigate whether brain age is an important factor in predicting conversion to dementia in patients with amyloid-negative amnestic MCI. We conducted a retrospective cohort study of patients with amyloid-negative amnestic MCI. All participants underwent detailed neuropsychological evaluation, brain magnetic resonance imaging (MRI), and [18F]-florbetaben positron emission tomography. Brain age was determined by the volumetric assessment of 12 distinct brain regions using an automatic segmentation software. During the follow-up period, 38% of the patients converted from amnestic MCI to dementia. Further, 73% of patients had a brain age greater than their actual chronological age. When defining 'survival' as the non-conversion of MCI to dementia, these groups differed significantly in survival probability (p = 0.036). The low-educated female group with a brain age greater than their actual age had the lowest survival rate among all groups. Our findings suggest that the MRI-based brain age used in this study can contribute to predicting conversion to dementia in patients with amyloid-negative amnestic MCI.

Predicting amyloid PET positivity using plasma p-tau181 and other blood-based biomarkers.

Introduction: This study aimed to determine the efficacy of combining plasma phosphorylated tau (p-tau)181, amyloid beta (Aß)42/Aß40, neurofilament light (NfL), and apolipoprotein E (APOE) genotypes for detecting positive amyloid positron emission tomography (PET), which is little known in the Asian population, in two independent cohorts. Methods: Biomarkers were measured using a single-molecule array (Simoa) in a cohort study (Asan). All participants underwent amyloid PET. Significant changes in the area under the curve (AUC) and Akaike Information Criterion values were considered to determine the best model. The generalizability of this model was tested using another cohort (KBASE-V). Results: In the Asan cohort, after adjusting for age and sex, p-tau181 (AUC = 0.854) or APOE ε4 status (AUC = 0.769) distinguished Aß status with high accuracy. Combining them or adding NfL and Aß42/40 improved model fitness. The best-fit model included the plasma p-tau181, APOE ε4, NfL and Aß42/40. The models established from the Asan cohort were tested in the KBASE-V cohort. Additionally, in the KBASE-V cohort, these three biomarker models had similar AUC in cognitively unimpaired (AUC = 0.768) and mild cognitive impairment (MCI) (AUC = 0.997) participants. Conclusions: Plasma p-tau181 showed a high performance in determining Aß-PET positivity. Adding plasma NfL and APOE ε4 status improved the model fit without significant improvement in AUC.

Do radiomics or diffusion-tensor images provide additional information to predict brain amyloid-beta positivity?

The aim of the present study was to predict amyloid-beta positivity using a conventional T1-weighted image, radiomics, and a diffusion-tensor image obtained by magnetic resonance imaging (MRI). We included 186 patients with mild cognitive impairment (MCI) who underwent Florbetaben positron emission tomography (PET), MRI (three-dimensional T1-weighted and diffusion-tensor images), and neuropsychological tests at the Asan Medical Center. We developed a stepwise machine learning algorithm using demographics, T1 MRI features (volume, cortical thickness and radiomics), and diffusion-tensor image to distinguish amyloid-beta positivity on Florbetaben PET. We compared the performance of each algorithm based on the MRI features used. The study population included 72 patients with MCI in the amyloid-beta-negative group and 114 patients with MCI in the amyloid-beta-positive group. The machine learning algorithm using T1 volume performed better than that using only clinical information (mean area under the curve [AUC]: 0.73 vs. 0.69, p < 0.001). The machine learning algorithm using T1 volume showed better performance than that using cortical thickness (mean AUC: 0.73 vs. 0.68, p < 0.001) or texture (mean AUC: 0.73 vs. 0.71, p = 0.002). The performance of the machine learning algorithm using fractional anisotropy in addition to T1 volume was not better than that using T1 volume alone (mean AUC: 0.73 vs. 0.73, p = 0.60). Among MRI features, T1 volume was the best predictor of amyloid PET positivity. Radiomics or diffusion-tensor images did not provide additional benefits.

Effect of toothpaste tablets on gloss and surface roughness of resin-based composite materials.

PURPOSE: To evaluate the effects of toothpaste tablets on the gloss and surface roughness of resin-based composite materials and determine the relationship between gloss and roughness. METHODS: Rectangular jigs were designed and printed. Wells (2 mm deep x 7 mm diameter) were filled with Filtek Supreme Ultra A2B, light-cured and polished. A small-area glossmeter was used for gloss (GU) measurements and a profilometer for roughness measurements (Ra) at baseline and after challenge with each toothpaste. An automated tooth-brushing machine was set at 120 strokes/minute for a total of 10,000 strokes to evaluate four test groups with 16 specimens in each group. NC: Brushing with distilled water; TABS: Colgate Anywhere Travel Tooth Tabs; CP: Colgate Cavity Protection Toothpaste and AW: Colgate Whitening Advanced Toothpaste. Kruskal-Wallis test was used to test the difference in gloss and surface roughness among the groups and Pearson correlation was used to compare the relationship between gloss and roughness. RESULTS: There was no statistically significant difference in gloss and roughness among the four groups at baseline. At post-brushing, there was a statistically significant difference among the groups (P< 0.001) with increased roughness and decreased gloss for CP and AW when compared to TABS. There was a statistically significant correlation between post-brushing roughness and post-brushing gloss (P< 0.001, rho: -0.815). Thus, the higher the surface roughness the lower the gloss. CLINICAL SIGNIFICANCE: Toothpaste tablets retain better gloss and roughness of resin-based composite materials when compared to conventional toothpastes.

Concurrent Validity of Dual-Task Walking Speed With CERAD-NP Assessment Battery in Community-Dwelling Older Adults.

Objective: To explore the concurrent validity of the dual-task walking speed assessments in older adults using the Consortium to Establish a Registry for Alzheimer's Disease Neuro-Psychological (CERAD-NP) Assessment Battery. Design: Cross-sectional design. Setting: Welfare care centers, Senior complex centers, and Dementia prevention care centers. Participants: A total of 163 community-dwelling older adults (N=163) were recruited using consecutive sampling. Participants were composed of 65 older adults with cognitive decline and 98 without cognitive decline. Interventions: Not applicable. Main Outcome Measures: This study assessed the concurrent validity between dual-task walking speed assessments and the Total II score of CERAD-NP using Spearman's rank order correlations. The effect of the dual-task walking speed assessments on the Total II score was further investigated through multiple linear regression analysis. Results: There was a moderate and statically significant association between the Total II score and all 8 dual-task walking speed assessments (P<.05). The Total II score was strongly associated with the dual tasks of walking on a straight path while counting backward and crossing over an obstacle (r=0.698, r=0.697, respectively; P<.05). According to multiple linear regression, only the dual task of walking while counting backward was significantly associated with the Total II score (P<.05). Conclusion: The dual-task walking speed assessments, which involved walking and performing a secondary task such as counting backward or crossing an obstacle on a straight path, were highly indicative of cognitive decline. The combination of results from both tasks may provide a more comprehensive evaluation of cognitive decline compared with relying solely on a single-task assessment.

The impact of subthreshold levels of amyloid deposition on conversion to dementia in patients with amyloid-negative amnestic mild cognitive impairment.

BACKGROUND: About 40-50% of patients with amnestic mild cognitive impairment (MCI) are found to have no significant Alzheimer's pathology based on amyloid PET positivity. Notably, conversion to dementia in this population is known to occur much less often than in amyloid-positive MCI. However, the relationship between MCI and brain amyloid deposition remains largely unknown. Therefore, we investigated the influence of subthreshold levels of amyloid deposition on conversion to dementia in amnestic MCI patients with negative amyloid PET scans. METHODS: This study was a retrospective cohort study of patients with amyloid-negative amnestic MCI who visited the memory clinic of Asan Medical Center. All participants underwent detailed neuropsychological testing, brain magnetic resonance imaging, and [18F]-florbetaben (FBB) positron emission tomography scan (PET). Conversion to dementia was determined by a neurologist based on a clinical interview with a detailed neuropsychological test or a decline in the Korean version of the Mini-Mental State Examination score of more than 4 points per year combined with impaired activities of daily living. Regional cortical amyloid levels were calculated, and a receiver operating characteristic (ROC) curve for conversion to dementia was obtained. To increase the reliability of the results of the study, we analyzed the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset together. RESULTS: During the follow-up period, 36% (39/107) of patients converted to dementia from amnestic MCI. The dementia converter group displayed increased standardized uptake value ratio (SUVR) values of FBB on PET in the bilateral temporal, parietal, posterior cingulate, occipital, and left precuneus cortices as well as increased global SUVR. Among volume of interests, the left parietal SUVR predicted conversion to dementia with the highest accuracy in the ROC analysis (area under the curve [AUC] = 0.762, P < 0.001). The combination of precuneus, parietal cortex, and FBB composite SUVRs also showed a higher accuracy in predicting conversion to dementia than other models (AUC = 0.763). Of the results of ADNI data, the SUVR of the left precuneus SUVR showed the highest AUC (AUC = 0.596, P = 0.006). CONCLUSION: Our findings suggest that subthreshold amyloid levels may contribute to conversion to dementia in patients with amyloid-negative amnestic MCI.

Patterns of Focal Amyloid Deposition Using 18F-Florbetaben PET in Patients with Cognitive Impairment.

Accumulation of aggregated amyloid-ß (Aß) in the brain is considered the first pathological event within the pathogenesis of Alzheimer's disease (AD). It is difficult to accurately identify the initial brain regions of Aß accumulation due to the time-lag between the start of the pathophysiology and symptom onset. However, focal regional amyloid uptake on amyloid PET scans may provide insights into this. Hence, we aimed to evaluate the topographic distribution of amyloid deposition in patients with cognitive impairment and to identify the starting order of amyloid accumulation in the brain using conditional probability. We enrolled 58 patients composed of 9 normal cognition (NC), 32 mild cognitive impairment (MCI), and 17 dementia showing focal regional amyloid deposition corresponding to a brain amyloid plaque load (BAPL) score of 2 among those who visited the Memory Clinic of Asan Medical Center and underwent an 18F-florbetaben PET scan (March 2013 to April 2019). Regions of interest (ROI) included the frontal, parietal, lateral temporal, and occipital cortices, the posterior cingulate/precuneus, and the striatum. The most frequent occurrence of Aß deposition was in the posterior cingulate/precuneus (n = 41, 68.3%). The second most frequent site was the lateral temporal cortex (n = 24, 40.0%), followed by the lateral parietal cortex (n = 21, 35.6%) and other lesions, such as the frontal and occipital cortices. The striatum was the least frequently affected. Our study found that the posterior cingulate/precuneus and the lateral temporal and parietal cortices may be the earliest areas to be affected by Aß accumulation. Longitudinal follow-up of focal brain amyloid deposition may help elucidate the evolutionary pattern of Aß accumulation in the brain of people with AD continuum.

Role of White Matter Abnormalities in the Relationship Between Microbleed Burden and Cognitive Impairment in Cerebral Amyloid Angiopathy.

BACKGROUND: Cerebral amyloid angiopathy (CAA) often presents as cognitive impairment, but the mechanism of cognitive decline is unclear. Recent studies showed that number of microbleeds were associated with cognitive decline. OBJECTIVE: We aimed to investigate how microbleeds contribute to cognitive impairment in association with white matter tract abnormalities or cortical thickness in CAA. METHODS: This retrospective comparative study involved patients with probable CAA according to the Boston criteria (Aß+ CAA) and patients with Alzheimer's disease (Aß+ AD), all of whom showed severe amyloid deposition on amyloid PET. Using mediation analysis, we investigated how FA or cortical thickness mediates the correlation between the number of lobar microbleeds and cognition. RESULTS: We analyzed 30 patients with Aß+ CAA (age 72.2±7.6, female 53.3%) and 30 patients with Aß+ AD (age 71.5±7.6, female 53.3%). The two groups showed similar degrees of cortical amyloid deposition in AD-related regions. The Aß+ CAA group had significantly lower FA values in the clusters of the posterior area than did the Aß+ AD group(family-wise error-corrected p < 0.05). The correlation between the number of lobar microbleeds and visuospatial function was indirectly mediated by white matter tract abnormality of right posterior thalamic radiation (PTR) and tapetum, while lobar microbleeds and language function was indirectly mediated by the abnormality of left PTR and sagittal stratum. Cortical thickness did not mediate the association between lobar microbleeds and cognition. CONCLUSION: This result supports the hypothesis that microbleeds burden leads to white matter tract damage and subsequent cognitive decline in CAA.

Crossed Hemispheric Accumulation of ß-Amyloid and Tau Protein in a Patient With Typical Alzheimer Disease.

Amyloid (Aß) and tau proteins are pathologic hallmarks of Alzheimer disease (AD). It is well known that there is spatial disparity between Aß and tau protein deposition but, crossed hemispheric accumulation of these 2 proteins has not been reported. Here we report the case of a 76-year-old woman with typical AD who underwent amyloid positron emission tomography (PET) ([ 18 F]-florbetaben) and tau PET scans ([ 18 F]PI-2620), revealing crossed accumulation of Aß and tau in the cerebral hemisphere. A neuropsychological assessment showed impairment in memory with spared activities of daily living. In the PET analysis, amyloid deposition was observed only in the left side of the cerebral hemisphere and tau only in the right side. Neuroimaging follow-up indicated that the spatial pattern of these protein accumulations had not changed. This case suggests the possibility of independent Aß and tau pathogenic pathways in AD.

Development of a Low-Molecular-Weight Aß42 Detection System Using a Enzyme-Linked Peptide Assay.

Alzheimer's disease (AD) is a degenerative brain disease that is the most common cause of dementia. The incidence of AD is rapidly rising because of the aging of the world population. Because AD is presently incurable, early diagnosis is very important. The disease is characterized by pathological changes such as deposition of senile plaques and decreased concentration of the amyloid-beta 42 (Aß42) peptide in the cerebrospinal fluid (CSF). The concentration of Aß42 in the CSF is a well-studied AD biomarker. The specific peptide probe was screened through four rounds of biopanning, which included the phage display process. The screened peptide showed strong binding affinity in the micromolar range, and the enzyme-linked peptide assay was optimized using the peptide we developed. This diagnostic method showed specificity toward Aß42 in the presence of other proteins. The peptide-binding site was also estimated using molecular docking analysis. Finally, the diagnostic method we developed could significantly distinguish patients who were classified based on amyloid PET images.

Effects of Body Weight on the Safety of High-Dose Donepezil in Alzheimer's Disease: Post hoc Analysis of a Multicenter, Randomized, Open-Label, Parallel Design, Three-Arm Clinical Trial.

BACKGROUND: Donepezil 23 mg is considered for Alzheimer's disease (AD) to optimize cognitive benefits; however, increased adverse events (AEs) can negatively influence drug adherence. We investigated whether body weight (BW) differs based on the presence of AEs, and which baseline factors were relevant to the safety of high-dose donepezil. METHODS: This study was a post hoc analysis of a multicenter randomized trial between 2014 and 2016. We included patients with moderate to severe AD treated with 10 mg/day of donepezil, and the daily dose was escalated to 23 mg with/without dose titration. Dose titration indicates 15 mg/day of donepezil before escalation or 10 mg and 23 mg/day on alternate days before escalation during the first 4 weeks. The patients were divided into 2 groups based on occurrence of AEs of special interest (AESIs) to compare baseline characteristics. We also assessed relationships between BW and AESIs. RESULTS: Among the 160 participants in the safety population, the baseline BWs differed between the AESI (+) (n = 67) and AESI (-) (n = 93) groups. Baseline BW was inversely correlated with the occurrence of AESIs (p = 0.020), and this relationship was prominent in the no-dose titration group (p = 0.009) but absent in the dose-titration groups (p > 0.05). CONCLUSIONS: BW is the most important factor that correlated with cholinergic AEs. Hence, stepwise dose titration should be considered, particularly in patients with low BW, to minimize the inverse relationship between BW and the occurrence of AEs ("Clinicaltrials.gov" No. NCT02550665 registered on September 15, 2015).

False Memory and Alzheimer's Disease Pathology in Patients with Amnestic Mild Cognitive Impairment: A Study with Amyloid PET.

INTRODUCTION: False memory, observed as intrusion errors or false positives (FPs), is prevalent in patients with Alzheimer's disease, but has yet to be thoroughly investigated in patients with amnestic mild cognitive impairment (a-MCI) with Alzheimer's disease pathology (ADP). We analyzed false versus veridical memory in individuals with a-MCI and measured the utility of false memory for ADP discrimination. METHODS: Patients with a-MCI who received neuropsychological testing and amyloid PET were included. Patients were categorized into "with" and "without ADP" groups according to PET results. Memory tests assessed veridical and false memory, and the verity of patient responses was analyzed. A logistic regression model was used to evaluate false memory efficiency in discriminating ADP, and the sensitivity and specificity at the optimal level were estimated using the receiver-operating characteristic curve. RESULTS: Thirty-seven ADP and 46 non-ADP patients were enrolled. The ADP group made more FPs in the recognition tests, and their response verity was significantly lower in every delayed memory test. No group difference, however, was observed in the veridical memory. The logistic regression analysis demonstrated that as the FPs increased, the risk of ADP increased 1.31 and 1.36 times in the verbal and visual recognition tests, respectively. The discriminatory accuracy of the FPs was estimated "low" to "moderate" in the visual and verbal recognition, respectively, with an optimal cutoff above 2.5. CONCLUSION: Increased false memory was the only feature to discriminate ADP from non-ADP in individuals with a-MCI. Further studies regarding false memory and its mechanism are warranted.

The relationship of soluble TREM2 to other biomarkers of sporadic Alzheimer's disease.

Microglial activation is a central player in the pathophysiology of Alzheimer's disease (AD). The soluble fragment of triggering receptor expressed on myeloid cells 2 (sTREM2) can serve as a marker for microglial activation and has been shown to be overexpressed in AD. However, the relationship of sTREM2 with other AD biomarkers has not been extensively studied. We investigated the relationship between cerebrospinal fluid (CSF) sTREM2 and other AD biomarkers and examined the correlation of plasma sTREM2 with CSF sTREM2 in a cohort of individuals with AD and without AD. Participants were consecutively recruited from Asan Medical Center from 2018 to 2020. Subjects were stratified by their amyloid positivity and clinical status. Along with other AD biomarkers, sTREM2 level was measured in the plasma as well as CSF. In 101 patients with either amyloid-positive or negative status, CSF sTREM2 was closely associated with CSF T-tau and P-tau and not with Abeta42. CSF sTREM2 levels were found to be strongly correlated with CSF neurofilament light chain. The comparison of CSF and plasma sTREM2 levels tended to have an inverse correlation. Plasma sTREM2 and P-tau levels were oppositely influenced by age. Our results suggest that neuroinflammation may be closely associated with tau-induced neurodegeneration.

Early Impairment in the Ventral Visual Pathway Can Predict Conversion to Dementia in Patients With Amyloid-negative Amnestic Mild Cognitive Impairment.

BACKGROUND: Around 15% to 20% of patients with clinically probable Alzheimer disease have been found to have no significant Alzheimer pathology on amyloid positron emission tomography. A previous study showed that conversion to dementia from amyloid-negative mild cognitive impairment (MCI) was observed in up to 11% of patients, drawing attention to this condition. OBJECT: We gathered the detailed neuropsychological and neuroimaging data of this population to elucidate factors for conversion to dementia from amyloid-negative amnestic MCI. METHODS: This study was a single-institutional, retrospective cohort study of amyloid-negative MCI patients over age 50 with at least 36 months of follow-up. All subjects underwent detailed neuropsychological testing, 3 tesla brain magnetic resonance imaging), and fluorine-18(18F)-florbetaben amyloid positron emission tomography scans. RESULTS: During the follow-up period, 39 of 107 (36.4%) patients converted to dementia from amnestic MCI. The converter group had more severe impairment in all visual memory tasks. The volumetric analysis revealed that the converter group had significantly reduced total hippocampal volume on the right side, gray matter volume in the right lateral temporal, lingual gyri, and occipital pole. CONCLUSION: Our study showed that reduced gray matter volume related to visual memory processing may predict clinical progression in this amyloid-negative MCI population.

FDG-PET patterns associated with ideomotor apraxia and imitation apraxia in patients with corticobasal syndrome.

INTRODUCTION: Apraxia is a core clinical feature of corticobasal syndrome (CBS). Among the subtypes of apraxia, ideomotor and imitation apraxia are frequently found in CBS. However, little is known about the brain networks that are characteristic of each apraxia subtype or their clinical implication. In this study, we used 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) to explore the specific patterns of glucose hypometabolism that are characteristic of apraxia subtypes by focusing on ideomotor and imitation apraxia. METHODS: We compared the areas of glucose hypometabolism in the brains of 52 patients with CBS and 13 healthy controls, both as a whole and according to apraxia subtypes. In addition, we investigated the relationship between the apraxia subtypes and the clinical phenotype of CBS. RESULTS: In patients with CBS, common hypometabolism was observed in the frontal gyrus, precentral gyrus and caudate regardless of apraxia subtypes. In particular, ideomotor apraxia was associated with hypometabolism in the angular gyrus, while imitation apraxia was associated with hypometabolism in the posterior part including the postcentral gyrus, precuneus, and posterior cingulate gyrus. Patients who showed both ideomotor and imitation apraxia were more likely to show the typical features of CBS and progressive supranuclear palsy compared with patients showing only one type of apraxia. CONCLUSION: Group comparison analysis using FDG-PET revealed distinct pathways of ideomotor and imitation apraxia in CBS. These findings add to our understanding of the brain networks underlying apraxia in association with the clinical features of CBS.

Biphasic Production of Anti-ApoB100 Autoantibodies in Obese Humans and Mice.

Obesity is associated with autoimmunity, a phenomenon considered as harmful. Here we show that obese mice and humans produce IgG-type autoantibodies that specifically recognize apolipoprotein B-100 (ApoB100), its native epitope p210, and the synthetic p210 mimotope pB1. By contrast, antibodies against epitopes p45 and p240, which have been associated with atherosclerosis, were not detected in either the humans or mice. In a longitudinal analysis of high fat diet-fed mice, autoantibody production rose with increasing body weight, then decreased and plateaued at morbid obesity. Likewise, in a cross-sectional analysis of sera from 148 human volunteers spanning a wide BMI range and free of comorbidities, the immunoreactivity increased and then decreased with increasing BMI. Thus, the obesity-related ApoB100-specific natural autoantibodies characteristically showed the same epitope recognition, IgG-type, and biphasic serum levels in humans and mice. We previously reported that a pB1-based vaccine induces similar antibodies and can prevent obesity in mice. Therefore, our present results suggest that autoantibodies directed against native ApoB100 may mitigate obesity, and that the vaccination approach may be effective in humans.

The cerebellum could serve as a potential imaging biomarker of dementia conversion in patients with amyloid-negative amnestic mild cognitive impairment.

BACKGROUND AND PURPOSE: As part of network-specific neurodegeneration, changes in cerebellar gray matter (GM) volume and impaired cerebello-cerebral functional networks have been reported in Alzheimer disease (AD). Compared with healthy controls, a volume loss in the cerebellum has been observed in patients with continuum of AD. However, little is known about the anatomical or functional changes in patients with clinical AD but no brain amyloidosis. We aimed to identify the relationship between cerebellar volume and dementia conversion of amyloid-negative mild cognitive impairment (MCI). METHODS: This study was a retrospective cohort study of patients over the age 50 years with amyloid-negative amnestic MCI who visited the memory clinic of Asan Medical Center with no less than a 36-month follow-up period. All subjects underwent detailed neuropsychological tests, 3 T brain magnetic resonance imaging scans including three-dimensional T1 imaging, and fluorine-18[F18 ]-florbetaben amyloid positron emission tomography scans. A spatially unbiased atlas template of the cerebellum and brainstem was used for analyzing cerebellar GM volume. RESULTS: During the 36 months of follow-up, 39 of 107 (36.4%) patients converted to dementia from amnestic MCI. The converter group had more severe impairments in all visual memory tasks. In terms of volumetric analysis, reduced crus I/II volume adjusted with total intracranial volume, and age was observed in the converter group. CONCLUSIONS: Significant cerebellar GM atrophy involving the bilateral crus I/II may be a novel imaging biomarker for predicting dementia progression in amyloid-negative amnestic MCI patients.