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Background and purpose: The co‐occurrence of amyloid‐β pathology in Parkinson's disease (PD) is common; however, the role of amyloid‐β deposition in motor prognosis remains elusive. This study aimed to investigate the association between striatal amyloid deposition, motor complications and motor prognosis in patients with PD. Methods: Ninety‐six patients with PD who underwent 18F florbetaben (FBB) positron emission tomography were retrospectively assessed. The ratio of the striatum to global (STG) FBB uptake was obtained for each individual, and patients were allotted into low and high STG groups according to the median value. The effect of STG group on regional amyloid deposition, the occurrence of motor complications and longitudinal change in levodopa equivalent dose (LED) requirement were investigated after controlling for age, sex, LED and disease duration at FBB scan. Results: The high STG group was associated with lower cortical FBB uptake in the parietal, occipital and posterior cingulate cortices and higher striatal FBB uptake compared to the low STG group. Patients in the high STG group had a higher risk of developing wearing off and levodopa‐induced dyskinesia than those in the low STG group, whereas the risk for freezing of gait was comparable between the two groups. The high STG group showed a more rapid increase in LED requirements over time than the low STG group. Conclusions: These findings suggest that relatively high striatal amyloid deposition is associated with poor motor outcomes in patients with PD. [ABSTRACT FROM AUTHOR]

Background: Dihydropyridines (DHPs) may have neuroprotective effects against Parkinson's disease (PD). Objective: This study investigated the effects of DHPs on nigrostriatal dopaminergic denervation and longitudinal motor and cognitive outcomes in PD. Methods: We classified 476 patients with drug‐naive PD who had undergone dopamine transporter imaging into three groups. They were selected according to a prior diagnosis of hypertension and use of DHPs and were matched using propensity scores: patients without hypertension (HTN−; n = 50) and patients with hypertension treated without DHP (HTN+/DHP−; n = 50) or with DHP (HTN+/DHP+; n = 50). Multiple linear regression and linear mixed model analyses were performed to determine intergroup differences in baseline dopamine transporter availability and longitudinal changes in the levodopa‐equivalent dose, respectively. Using Kaplan–Meier analyses, we compared the risks of levodopa‐induced dyskinesia, wearing off, and dementia‐free survival during the 5.06 years of the mean follow‐up period. The Cox regression model determined the independent effects of DHPs on dementia conversion. Results: Dopamine transporter availability in all striatal subregions was comparable between the HTN−, HTN+/DHP−, and HTN+/DHP+ groups. The risks of levodopa‐induced dyskinesia and wearing off, as well as longitudinal changes in the levodopa‐equivalent dose, did not differ between the groups. The HTN+/DHP+ group had a lower risk of developing dementia than the HTN+/DHP− (Bonferroni‐corrected Plog‐rank = 0.036) group. The use of DHP was independently associated with a lower risk of dementia conversion after controlling for other antihypertensive drugs and confounding factors (hazard ratio, 0.242; 95% confidence interval, 0.087–0.668; P = 0.006). Conclusions: DHPs may be associated with better long‐term cognitive outcomes in hypertensive patients with PD. © 2023 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Objective: Although growing evidence suggests that perivascular space (PVS) serves as a clearance route for amyloid and tau, the association between enlarged PVS (EPVS) and Alzheimer disease is highly inconsistent across studies. As the conventional visual rating systems for EPVS were insufficient to predict amyloid/tau/neurodegeneration (A/T/N) status, we developed a new rating scale for EPVS located in the temporal lobe (T‐EPVS). Methods: EPVS located in the basal ganglia (BG‐EPVS), centrum semiovale (CS‐EPVS), and T‐EPVS was visually rated in 272 individuals (healthy controls, n = 96; mild cognitive impairment, n = 106; dementia, n = 70) who underwent structural magnetic resonance imaging (MRI) and dual positron emission tomography scans (18F‐flortaucipir and 18F‐florbetaben). T‐EPVS and BG‐EPVS were defined as high degree when the counts in any hemisphere were >10, and the CS‐EPVS cutoff was >20. Logistic regression models were constructed to investigate whether the regional EPVS burden was predictive of A/T/N status. The derived models were externally validated in a temporal validation cohort (n = 195) that underwent MRI studies using a different scanner. Results: Compared with those with low‐degree T‐EPVS (23/136, 16.9%), individuals with high‐degree T‐EPVS/CS‐EPVS but low‐degree BG‐EPVS were more likely to exhibit amyloid positivity (46/56, 82.1%). High‐degree T‐EPVS burden (odds ratio [OR] = 7.251, 95% confidence interval [CI] = 3.296–15.952) and low‐degree BG‐EPVS (OR = 0.241, 95% CI = 0.109–0.530) were predictive of amyloid positivity. Although high‐degree T‐EPVS was associated with tau positivity, the association was no longer significant after adjusting for amyloid and neurodegeneration status. Interpretation: Investigating the burden and topographic distribution of EPVS including T‐EPVS may be useful for predicting amyloid status, indicating that impaired perivascular drainage may contribute to cerebral amyloidosis. ANN NEUROL 2023;93:965–978 [ABSTRACT FROM AUTHOR]

Background: Concomitant amyloid pathology contributes to the clinical heterogeneity of Lewy body diseases (LBDs). Objective: The objective of this study was to investigate the pattern and effect of amyloid accumulation on cognitive dysfunction in Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Methods: We retrospectively assessed 205 patients with LBD (91 with DLB and 114 with PD) who underwent 18F‐florbetaben positron emission tomography and divided them into amyloid‐positive and amyloid‐negative groups depending on global standardized uptake value ratios (SUVRs). We investigated the effect of group on the regional and global SUVRs using general linear models (GLMs) after controlling for age, sex, cognitive status, and score on the Korean version of the Mini‐Mental State Examination. Moreover, the effect of amyloid on cognitive function, depending on the type of LBD, was evaluated using GLMs with interaction analysis. Results: In all evaluated regions including the striatum, the DLB group showed a higher SUVR than the PD group. Among amyloid‐positive patients, the DLB group had a higher regional SUVR than the PD group in the frontal and parietal cortices. There was a significant interaction effect between amyloid and disease groups in language and memory function. In patients with PD, global amyloid load was negatively associated with language (B = −2.03; P = 0.010) and memory functions (B = −1.96; P < 0.001). However, amyloid load was not significantly associated with cognitive performance in the DLB group. Conclusions: Although the burden of amyloid was higher in the DLB group, amyloid accumulation was negatively associated with the memory and language functions in the PD group only. © 2022 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Objective: Considering the clinical heterogeneity of temporal lobe epilepsy with amygdala enlargement (TLE‐AE), identifying distinct prognostic subgroups of TLE‐AE has clinical implications. Until now, baseline volume of the enlarged amygdala (EAV) has consistently failed to predict prognosis in TLE‐AE. Based on studies suggesting that patients responsive to antiepileptic drugs (AEDs) exhibit remission of AE on follow‐up imaging, we investigated whether reduction rate of EAV is predictive of long‐term prognosis in TLE‐AE. Methods: Sixty‐one consecutive patients with two separate magnetic resonance imaging (MRI) scans were enrolled. To utilize longitudinally measured biomarkers in prediction, the period beyond the first MRI acquisition was split into two periods: the "observation window" (period between the two MRIs) and "prediction window" (follow‐up period beyond the second MRI). Patients were classified according to their AED responsiveness during the observation window, and AED‐responsive patients were further subdivided by initial seizure frequency: (a) AED‐responsive patients presenting with low‐frequency seizures (<5 seizures/3 mo; Group A, n = 25), (b) high‐frequency seizures (≥5 seizures/3 mo; Group B, n = 23), and (c) patients with poor initial treatment response (Group C, n = 13). Multivariate logistic regression models were constructed for identification of prognostic factors. Along with factors obtained at baseline, factors derived from the observation window (annual percentage change of EAV [APCEAV] and initial AED responsiveness) were also considered as potential predictors. Results: Favorable initial treatment response and faster volume reduction rate (APCEAV ≤ −5.0%/y) were identified as factors predictive of achieving overall seizure freedom. Among the AED‐responsive patients, Group A (low‐frequency seizures) showed slower remission of AE and higher rate of seizure recurrence, whereas Group B (high‐frequency seizures) exhibited faster remission of AE and lower rate of seizure recurrence. Significance: Faster recuperation of AE in patients with initial high‐frequency seizures may be indicative of seizure‐induced changes. As volume reduction rate serves as a prognostic marker in TLE‐AE, short‐term MRI follow‐up may be useful in prognostication. [ABSTRACT FROM AUTHOR]

Background: Accumulating data suggests that MRI‐visible enlarged PVS (ePVS) may serve as an imaging marker of glymphatic dysfunction. Until now, ePVS in various regions such as basal ganglia (BG‐ePVS) or centrum semiovale (CS‐ePVS) have been introduced and their topographic distributions are recognized as a marker to differentiate the underlying etiologies, although they failed to predict amyloid‐positivity. As the conventional classification of ePVS was insufficient to predict Alzheimer pathologies, we developed a new grading system for ePVS located at the temporal lobe (T‐ePVS), a strategic region where both amyloid and tau overlaps in their early stages. We investigated whether amyloid‐positivity or tau‐positivity is associated with T‐ePVS along with other conventional ePVS markers. Method: ePVS were manually counted on magnetic resonance (MR) images obtained from 272 participants (cognitively normal, n=96; cognitively impaired, n=176) who underwent dual PET scans (18F‐flortaucipir and 18F‐florbetaben). T‐ePVS and BG‐ePVS were defined as “extensive” when the counts in any hemisphere were >10, while the cutoff of CS‐ePVS was >20. Subjects were grouped based on the combinations of the severity of region‐specific ePVS and their relationship with amyloid‐/tau‐positivity were investigated. Moreover, logistic regression models were constructed to investigate whether severity of region‐specific ePVS were predictive of amyloid‐ or tau‐positivity. Result: Compared to those with low T‐ePVS burden (21/136, 15.4%), subjects with high T‐ePVS burden were more likely to show amyloid‐positivity (89/136, 65.4%). Among the 8 groups based on region‐specific ePVS burden, subjects with high T‐/CS‐ePVS but low BG‐ePVS burden showed highest amyloid‐positivity (46/56, 82.3%). Furthermore, high T‐ePVS burden (Odds ratio [OR]=7.458; 95% confidence interval [CI]=3.387‐16.419), low BG‐ePVS burden (OR=0.238; 95% CI=0.108‐0.524), and APOE ε4 allele presence (OR=5.175; 95% CI=2.444‐10.959) were significantly associated with amyloid‐positivity. Similar results were reproduced when the analyses were performed within subjects with cognitive impairment. Within the amyloid‐positive subjects, subjects with high CS‐ePVS but low BG‐ePVS burden were likely to exhibit tau‐positivity, while the severity of each region‐specific ePVS were not independently predictive of tau‐positivity. Conclusion: Our findings suggest that investigating the load and topographic distribution of ePVS based on MR images may be useful for predicting amyloid‐ and tau‐positivity, suggesting that glymphatic dysfunction may contribute to Alzhiemer’s pathogenesis. [ABSTRACT FROM AUTHOR]