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Objective: This study investigated cerebral small vessel disease (CSVD) damage patterns in early‐onset and late‐onset Alzheimer's disease (EOAD and LOAD) and their effects on cognitive function. Methods: This study included 93 participants, 45 AD patients (14 EOAD and 31 LOAD), and 48 normal controls (13 YNC and 35 ONC) from the ADNI database. All participants had diffusion tensor imaging data; some had amyloid PET and plasma p‐tau181 data. The study used peak width of skeletonized mean diffusivity (PSMD) to measure CSVD severity and compared PSMD between patients and age‐matched controls. The effect of age on the relationship between PSMD and cognition was also examined. The study also repeated the analysis in amyloid‐positive AD patients and amyloid‐negative controls in another independent database (31 EOAD and 38 LOAD), and the merged database. Results: EOAD and LOAD showed similar cognitive function and disease severity. PSMD was validated as a reliable correlate of cognitive function. In the ADNI database, PSMD was significantly higher for LOAD and showed a tendency to increase for EOAD; in the independent and merged databases, PSMD was significantly higher for both LOAD and EOAD. The impact of PSMD on cognitive function was notably greater in the younger group (YNC and EOAD) than in the older group (ONC and LOAD), as supported by the ADNI and merged databases. Interpretation: EOAD has less CSVD burden than LOAD, but has a greater impact on cognition. Proactive cerebrovascular prevention strategies may have potential clinical value for younger older adults with cognitive decline. [ABSTRACT FROM AUTHOR]

Concomitant neuropsychiatric symptoms (NPS) are associated with accelerated Alzheimer's disease (AD) progression. Identifying multimodal brain imaging patterns associated with NPS may help understand pathophysiology correlates AD. Based on the AD continuum, a supervised learning strategy was used to guide four‐way multimodal neuroimaging fusion (Amyloid, Tau, gray matter volume, brain function) by using NPS total score as the reference. Loadings of the identified multimodal patterns were compared across the AD continuum. Then, regression analyses were performed to investigate its predictability of longitudinal cognition performance. Furthermore, the fusion analysis was repeated in the four NPS subsyndromes. Here, an NPS‐associated pathological–structural–functional covaried pattern was observed in the frontal‐subcortical limbic circuit, occipital, and sensor‐motor region. Loading of this multimodal pattern showed a progressive increase with the development of AD. The pattern significantly correlates with multiple cognitive domains and could also predict longitudinal cognitive decline. Notably, repeated fusion analysis using subsyndromes as references identified similar patterns with some unique variations associated with different syndromes. Conclusively, NPS was associated with a multimodal imaging pattern involving complex neuropathologies, which could effectively predict longitudinal cognitive decline. These results highlight the possible neural substrate of NPS in AD, which may provide guidance for clinical management. [ABSTRACT FROM AUTHOR]

Background: Apolipoprotein E (APOE) ε2 is a protective genetic factor for Alzheimer's disease (AD). However, the potential interaction effects between the APOE ε2 allele and disease status on the intrinsic brain activity remain elusive. Methods: We identified 73 healthy control (HC) with APOE ε3/ε3, 61 mild cognitive impairment (MCI) subjects with APOE ε3/ε3, 24 HC with APOE ε2/ε3, and 10 MCI subjects with APOE ε2/ε3 from the ADNI database. All subjects underwent a resting-state functional MRI and Fluoro-deoxy-glucose positron emission tomography (FDG-PET). We used a fractional amplitude of low-frequency fluctuation (fALFF) to explore the spontaneous brain activity. Based on the mixed-effects analysis, we explored the interaction effects between the APOE ε2 allele versus disease status on brain activity and metabolism in a voxel-wise fashion (GRF corrected, p < 0.01), followed by post hoc two-sample t -tests (Bonferroni corrected, p < 0.05). We then investigated the relationship between the mean imaging metrics and cognitive abilities. Results: There are no significant differences in gender, age, or education among the four groups. The interaction effect on brain activity was located in the inferior parietal lobule (IPL). Post hoc analysis showed that APOE ε2/ε3 MCI had an increased IPL fALFF than APOE ε3/ε3 MCI. Regarding the APOE ε2 allele effects, we found that ε2 carriers had a decreased fALFF in the transverse temporal gyrus than non-carriers. Also, FDG-PET results showed a lower SUVR of the frontal lobe in APOE ε2 carriers than non-carriers. Furthermore, fALFF of IPL was correlated with the visuospatial function (r = −0.16, p < 0.05). Conclusion: APOE ε2 carriers might have a better brain reservation when coping with AD-related pathologies. [ABSTRACT FROM AUTHOR]

Background: Predicting the prognosis of mild cognitive impairment (MCI) has outstanding clinical value, and the hippocampal volume is a reliable imaging biomarker of AD diagnosis.Objective: We aimed to longitudinally assess hippocampal sub-regional difference (volume and asymmetry) among progressive MCI (pMCI), stable MCI (sMCI) patients, and normal elderly.Methods: We identified 29 pMCI, 52 sMCI, and 102 normal controls (NC) from the ADNI database. All participants underwent neuropsychological assessment and 3T MRI scans three times. The time interval between consecutive MRI sessions was about 1 year. Volumes of hippocampal subfield were measured by Freesurfer. Based on the analysis of variance, repeated measures analyses, and receiver operating characteristic curves, we compared cross-sectional and longitudinal alteration sub-regional volume and asymmetry index.Results: Compared to NC, both MCI groups showed significant atrophy in all subfields. At baseline, pMCI have a smaller volume than sMCI in the bilateral subiculum, molecular layer (ML), the molecular and granule cell layers of the dentate gyrus, cornu ammonis 4, and right tail. Furthermore, repeated measures analyses revealed that pMCI patients showed a faster volume loss than sMCI in bilateral subiculum and ML. After controlling for age, gender, and education, most results remained unchanged. However, none of the hippocampal sub-regional volumes performed better than the whole hippocampus in ROC analyses, and no asymmetric difference between pMCI and sMCI was found.Conclusion: The faster volume loss in subiculum and ML suggest a higher risk of disease progression in MCI patients. The hippocampal asymmetry may have smaller value in predicting the MCI prognosis. [ABSTRACT FROM AUTHOR]

Background: Smoking is a modifiable risk factor for Alzheimer's disease (AD). However, smoking-related effects on intrinsic brain activity in high-risk AD population are still unclear. Objective: We aimed to explore differences in smoking effects on brain function between healthy elderly and amnestic mild cognitive impairment (aMCI) patients using ReHo mapping. Methods: We identified 64 healthy elderly controls and 116 aMCI patients, including 98 non-smoking and 18 smoking aMCI. Each subject underwent structural and resting-state functional MRI scanning and neuropsychological evaluations. Regional homogeneity (ReHo) mapping was used to assess regional brain synchronization. After correction for age, gender, education, and gray matter volume, we explored the difference of ReHo among groups in a voxel-wise way based on analysis of covariance (ANCOVA), followed by post hoc two-sample analyses (p < 0.05, corrected). Further, we correlated the mean ReHo with neuropsychological scales. Results: Three groups were well-matched in age, gender, and education. Significant ReHo differences were found among three groups, located in the left supramarginal gyrus (SMG) and left angular gyrus (AG). Specifically, non-smoking aMCI had lower ReHo in SMG and AG than smoking aMCI and controls. By contrast, smoking aMCI had greater AG ReHo than healthy controls (p < 0.05). Across groups, correlation analyses showed that left AG ReHo correlated with MMSE (r = 0.18, p = 0.015), clock drawing test (r = 0.20, p = 0.007), immediate recall (r = 0.36, p < 0.001), delayed recall (r = 0.34, p < 0.001), and auditory verbal learning test (r = 0.20, p = 0.007). Conclusion: Smoking might pose compensatory or protective effects on intrinsic brain activity in aMCI patients. [ABSTRACT FROM AUTHOR]