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Background: Alzheimer's disease (AD) is a neurodegenerative disease characterized by brain network dysfunction. Few studies have investigated whether the functional connections between executive control networks (ECN) and other brain regions can predict the therapeutic effect of repetitive transcranial magnetic stimulation (rTMS). Objective: The purpose of this study is to examine the relationship between the functional connectivity (FC) within ECN networks and the efficacy of rTMS. Methods: We recruited AD patients for rTMS treatment. We established an ECN using baseline period fMRI data and conducted an analysis of the ECN's FC throughout the brain. Concurrently, the support vector regression (SVR) method was employed to project post-rTMS cognitive scores, utilizing the connectional attributes of the ECN as predictive markers. Results: The average age of the patients was 66.86±8.44 years, with 8 males and 13 females. Significant improvement on most cognitive measures. We use ECN connectivity and brain region functions in baseline patients as features for SVR model training and fitting. The SVR model could demonstrate significant predictability for changes in Montreal Cognitive Assessment scores among AD patients after rTMS treatment. The brain regions that contributed most to the prediction of the model (the top 10% of weights) were located in the medial temporal lobe, middle temporal gyrus, frontal lobe, parietal lobe and occipital lobe. Conclusions: The stronger the antagonism between ECN and parieto-occipital lobe function, the better the prediction of cognitive improvement; the stronger the synergy between ECN and fronto-temporal lobe function, the better the prediction of cognitive improvement. [ABSTRACT FROM AUTHOR]

Background: Abnormalities in white matter (WM) may be a crucial physiologic feature of Alzheimer's disease (AD). However, neuroimaging's ability to visualize the underlying functional degradation of the WM region in AD is unclear. Objective: This study aimed to explore the differences in amplitude of low-frequency fluctuation (ALFF) and fractional ALFF (fALFF) in the WM region of patients with AD and healthy controls (HC) and to investigate further whether these values can provide supplementary information for diagnosing AD. Methods: Forty-eight patients with AD and 46 age-matched HC were enrolled and underwent resting-state functional magnetic resonance imaging and a neuropsychological battery assessment. We analyzed the differences in WM activity between the two groups and further explored the correlation between WM activity in the different regions and cognitive function in the AD group. Finally, a machine learning algorithm was adopted to construct a classifier in detecting the clinical classification ability of the values of ALFF/ALFF in the WM. Results: Compared with HCs, patients with AD had lower WM activity in the right anterior thalamic radiation, left frontal aslant tract, and left forceps minor, which are all positively related to global cognitive function, memory, and attention function (all p < 0.05). Based on the combined WM ALFF and fALFF characteristics in the different regions, individuals not previously assessed were classified with moderate accuracy (75%), sensitivity (71%), specificity (79%), and area under the receiver operating characteristic curve (85%). Conclusion: Our results suggest that WM activity is reduced in AD and can be used for disease classification. [ABSTRACT FROM AUTHOR]

Deficits in associative memory (AM) are the earliest and most prominent feature of Alzheimer's disease (AD) and demonstrate a clear cause of distress for patients and their families. The present study aimed to determine AM enhancements following accelerated intermittent theta-burst stimulation (iTBS) in patients with AD. In a randomized, double-blind, sham-controlled design, iTBS was administered to the left dorsolateral prefrontal cortex (DLPFC) of patients with AD for 14 days. Measurements included AM (primary outcome) and a comprehensive neuropsychological battery. Patients were evaluated at baseline, following the intervention (week 2), and 8 weeks after treatment cessation (week 10). Sixty patients with AD were initially enrolled; 47 completed the trial. The active group displayed greater AM improvements compared with the sham group at week 2 (P = 0.003), which was sustained at week 10. Furthermore, higher Mini-Mental State Examination (MMSE) scores at baseline were associated with greater AM improvements at weeks 2 and 10. For the independent iTBS group, this correlation predicted improvements in AM (P < 0.001) and identified treatment responders with 92% accuracy. Most of the neuropsychological tests were markedly improved in the active group. In particular, the Montreal Cognitive Assessment and MMSE in the active group increased by 2.8 and 2.3 points, respectively, at week 2, while there was no marked change in the sham group. In the present study, accelerated iTBS of the DLPFC demonstrated an effective and well-tolerated complementary treatment for patients with AD, especially for individuals with relatively high MMSE scores. • Accelerate iTBS of the left DLPFC showed an effective and well-tolerated complementary treatment to improve symptoms and cognitive in AD patients. • The MoCA and MMSE in active group increased 2.8 and 2.3 points after two-weeks treatment. • The ameliorating effects were more effective and robust among patients with high MMSE score in baseline. [ABSTRACT FROM AUTHOR]

Background : Alzheimer's disease (AD) manifests differently in males and females. However, the neuro-mechanism and influence factors are still unknown. Objective : To explore sex differences in brain network topology during AD disease progression and its association with cognition and possible influencing factors. Methods : Resting-state functional magnetic resonance imaging (MRI) data and cognitive scores were collected from 82 AD patients (50 females), 56 amnestic mildly cognitive impaired patients (29 females), and 63 healthy controls (38 females). Global and regional topological network metrics and modular architecture were calculated. Two-way ANOVA was performed to explore group and sex interactions and their main effects. Mediation analysis was used to explore the relationship among education, inter/intra-network connectivity, and the Mini-Mental State Examination (MMSE) score. Results : Lower levels of education, lower MMSE scores, and a positive correlation between the level of education and MMSE scores were found in female AD patients (p = 0.024, r = 0.319). Significantly lower connectivity strength within the sensorimotor network, dorsal attention network, ventral attention network (VAN), and between the sensorimotor and VAN were observed in male AD patients (p = 0.006, 0.028, 0.046, and 0.013, respectively). Group and sex interactions were also found in nodal properties, mainly in the frontal lobe, temporal lobe, middle cingulum, precuneus, and postcentral gyrus. Several of the altered brain network properties were associated with cognitive behavior in male AD patients. Education regulated the MMSE score through the mediation of connection strength between the default mode and limbic networks (LN) in the patient group (aMCI and AD combined). Conclusion : Our results demonstrate that sex differences exist at the brain network level in AD. Sex differences in network topology and education are correlated with sex differences in cognition during AD progression. [ABSTRACT FROM AUTHOR]

Background: There is increasing evidence that Alzheimer's disease (AD) patients may present decreased cerebral blood perfusion before pathological brain changes. Using the retina as a window to the brain, we can study disorders of the central nervous system through the eyes.Objective: This study aimed to investigate differences in retinal structure and vessel density (VD) between patients with mild AD and healthy controls (HCs). Furthermore, we explored the relationship between retinal VD and cognitive function.Methods: We enrolled 37 patients with AD and 29 age-matched HCs who underwent standard ophthalmic optical coherence tomography angiography (OCTA) for evaluation of the retinal layer thickness and VD parameters. Cognitive function was evaluated using a battery of neuropsychological assessments. Finally, the correlations among retinal layer thickness, VD parameters, and cognitive function were evaluated.Results: The retinal fiber layer thickness and retinal VD of patients with AD were significantly reduced compared with HCs. The retinal VD was significantly correlated with overall cognition, memory, executive, and visual-spatial perception functions. However, there was no significant between-group difference in the macular thickness.Conclusion: Our findings indicate a positive correlation between retinal VD and some, but not all, cognitive function domains. Most importantly, we demonstrated the role of OCTA in detecting early capillary changes, which could be a noninvasive biomarker for early AD. [ABSTRACT FROM AUTHOR]

Objective: Asymmetry is a subtle but pervasive aspect of the human brain, which may be altered in several neuropsychiatric conditions. Magnetic resonance imaging (MRI) studies have reported that cerebral structural asymmetries are altered in Alzheimer's disease (AD), but most of these studies were conducted at the region-of-interest level. At the functional level, there are few reports of resting-state functional asymmetries based on functional MRI. In this study, we investigated lateral differences in structural volumes and strengths of functional connectivity between individuals with AD and healthy controls (HCs) at the voxel level. Methods: Forty-eight patients with AD and 32 matched HCs were assessed. An analysis of voxel-based morphometry (VBM) of gray matter volume was performed at the whole-brain level to explore anatomical cerebral asymmetries in AD. We then performed a seed-to-whole-brain functional connectivity (FC) analysis to reveal FC asymmetries in AD. An asymmetry index (AI) was used to measure these changes, and the relationship between the structural and functional AIs and the clinical symptoms of AD was explored. Results: A VBM analysis revealed a rightward and a leftward lateralization in the amygdala and the thalamus, respectively, in patients with AD. FC between the amygdala and the precuneus showed a rightward lateralization in AD, which was the opposite of the lateralization in the HCs. The asymmetric changes in structure and function were associated with disease severity and functional impairment in AD. Conclusion: Our study highlights the value of considering asymmetries in the amygdala and the thalamus in clinical evaluations and their relevance to clinical measures. [ABSTRACT FROM AUTHOR]

Background : Alzheimer's disease (AD) is characterized by global deterioration in multiple cognitive domains. In addition to cognitive impairment, depressive symptoms are common issues that trouble AD patients. The neuroanatomical basis of depressive symptoms in AD patients has yet to be elucidated. Method : Twenty AD patients and 22 healthy controls (HCs) were recruited for the present study. Depressive symptoms in AD patients and HCs were assessed according to the Hamilton Depression Rating Scale (HDRS). Anatomical structural differences were assessed between AD patients and HCs using voxel-based morphometry (VBM) and surface-based morphometry (SBM). Correlation analyses were conducted to investigate relationships between depressive symptoms and structural altered regions. Multiple pattern analysis using linear support vector machine (SVM) was performed in another independent cohort, which was collected from Alzheimer's Disease Neuroimaging Initiative (ADNI) data and contained 20 AD patients and 20 HCs, to distinguish AD patients from HCs. Results : Compared with HCs, AD patients exhibited global cerebral atrophy in gray matter volume (GMV) and cortical thickness, including frontal, parietal, temporal, occipital, and insular lobes. In addition, insular GMV was negatively correlated with depressive symptoms. Moreover, SVM-based classification achieved an accuracy of 77.5%, a sensitivity of 70%, and a specificity of 85% by leave-one-out cross-validation. Conclusion : GMV of the insula displayed atrophy among AD patients, which is associated with depressive symptoms. Our observations provide a potential neural substrate for analysis to examine the co-occurrence of AD with depressive symptoms. [ABSTRACT FROM AUTHOR]

Intertemporal decision-making refers to selection among options with distinct consequences over time. Older adults have to make important decisions regarding health care and finances among other difficult issues with different shorter- and longer-term outcomes. Patients with Alzheimer's disease (AD) or mild cognitive impairment (MCI), a potential harbinger of AD, may make suboptimal decisions in complex situations, possibly due to impaired capacity for temporal discounting. This study aimed to evaluate intertemporal preferences in AD and MCI patients compared to healthy matched controls. AD or MCI patients and healthy control (HC) patients participated in a computerized, Chinese version of the Intertemporal Choice Task in which they were asked to choose between sooner-smaller (SS) and later-larger (LL) options in now-trials and not-now-trials. The main evaluation parameter was the percentage of choices for delayed rewards(%LL). AD or MCI patients tended to choose SS options in now-trials and not now-trials with greater frequency compared to HC patients. Additionally, AD and MCI patients demonstrated significantly poorer performance in several cognitive tests compared to healthy groups, including the Mini Mental State Exam (MMSE) and other tests of memory, attention and executive function. Correlational analysis revealed that poor intertemporal decision-making was associated with executive function deficits in MCI patients. Reduced intertemporal decision-making capacity in MCI may stem from impaired executive function, possibly due to frontal-parietal circuit degeneration. The cognitive and neurophysiological deficits underlying reduce decision-making capacity in AD warrant further investigation. [ABSTRACT FROM AUTHOR]

Background: Making advantageous decisions is essential in everyday life. Our objective was to assess how patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD) make decisions under conditions of ambiguity or risk. In addition, the study also aimed to examine the relationship between decision-making competence and memory and executive function. Methods: Patients with MCI (n = 36) and AD (n = 29) and healthy elderly controls (HC, n = 34) were recruited from the memory clinic. All subjects were administered a comprehensive neuropsychological battery test. We used the Iowa Gambling Task (IGT) to measure decision-making under ambiguity and the Game of Dice Task (GDT) to measure decision-making under risk. Pearson's correlation was used to examine the relationship between the performance of IGT and GDT with delayed recall and the Stroop test. Results: In the GDT, MCI and AD patients presented similar performance but showed different patterns when compared with the HC group. The proportion of those making advantageous choices was lower in the AD group than in the HC group (p = 0.01), while the MCI and HC groups did not differ (p = 0.14). Meanwhile, concerning the ratio of accepting negative feedback, the AD (p < 0.01) group was significantly different from the HC patients, but the MCI (p = 0.06) and HC groups did not differ. In the IGT, MCI and AD patients selected randomly from advantageous and disadvantageous decks (p = 0.94 and p = 0.54), showing no significant change in performance over time. In contrast, the HC group made increasingly frequent advantageous selections over time (p = 0.04). Furthermore, the proportion of advantageous decision-makers for the GDT had a linear relationship with delayed recall of the Hopkins Verbal Learning Test and Stroop color words (p < 0.01 and p < 0.01, respectively). Conclusion: Our findings suggest that decision-making ability under ambiguity is compromised in MCI and AD, and the decision-making under risk is only impaired in AD. Reduced decision-making performance under risk is closely correlated with lower executive functions and memory. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a common memory-impairment disorder frequently accompanied by olfactory identification (OI) impairments. In fact, OI is a valuable marker for distinguishing AD from normal age-related cognitive impairment and may predict the risk of mild cognitive impairment (MCI)-to-AD transition. However, current olfactory tests were developed based on Western social and cultural conditions, and are not very suitable for Chinese patients. Moreover, the neural substrate of OI in AD is still unknown. The present study investigated the utility of a newly developed Chinese smell identification test (CSIT) for OI assessment in Chinese AD and MCI patients. We then performed a correlation analysis of gray matter volume (GMV) at the voxel and region-of-interest (ROI) levels to reveal the neural substrates of OI in AD. Thirty-seven AD, 27 MCI, and 30 normal controls (NCs) completed the CSIT and MRI scans. Patients (combined AD plus MCI) scored significantly lower on the CSIT compared to NCs [ F (2,91) = 62.597, p < 0.001)]. Voxel-level GMV analysis revealed strong relationships between CSIT score and volumes of the left precentral gyrus and left inferior frontal gyrus (L-IFG). In addition, ROI-level GMV analysis revealed associations between CSIT score and left amygdala volumes. Our results suggest the following: (1) OI, as measured by the CSIT, is impaired in AD and MCI patients compared with healthy controls in the Chinese population; (2) the severity of OI dysfunction can distinguish patients with cognitive impairment from controls and AD from MCI patients; and (3) the left-precentral cortex and L-IFG may be involved in the processing of olfactory cues. [ABSTRACT FROM AUTHOR]

Abstract: Explicit memory has been well proven to be impaired in amnestic mild cognitive impairment (aMCI), and conceptual implicit memory is impaired in Alzheimer''s disease. However, it is unclear whether implicit memory is affected in aMCI. In the present study, 35 patients with aMCI and 35 healthy elderly subjects were administered a neuropsychological battery of tests including conceptual and perceptual implicit memory tasks (category exemplar generation, image identification) as well as explicit memory tasks. Patients with aMCI exhibited impairment in explicit memory tasks and selective impairment in conceptual priming tasks, while the effect of perceptual priming was preserved. More importantly, category exemplar generation task priming, but not perceptual priming, was positively correlated with verbal fluency test performance in the aMCI group. The dissociation between the 2 components of implicit priming suggests that conceptual priming impairment in aMCI patients may be related to frontal lobe dysfunction. [Copyright &y& Elsevier]

Background: Cerebral specialization and interhemispheric cooperation are two vital features of the human brain. Their dysfunction may be associated with disease progression in patients with Alzheimer's disease (AD), which is featured as progressive cognitive degeneration and asymmetric neuropathology. Objective: This study aimed to examine and define two inherent properties of hemispheric function in patients with AD by utilizing resting‐state functional magnetic resonance imaging (rs‐fMRI). Methods: Sixty‐four clinically diagnosed AD patients and 52 age‐ and sex‐matched cognitively normal subjects were recruited and underwent MRI and clinical evaluation. We calculated and compared brain specialization (autonomy index, AI) and interhemispheric cooperation (connectivity between functionally homotopic voxels, CFH). Results: In comparison to healthy controls, patients with AD exhibited enhanced AI in the left middle occipital gyrus. This increase in specialization can be attributed to reduced functional connectivity in the contralateral region, such as the right temporal lobe. The CFH of the bilateral precuneus and prefrontal areas was significantly decreased in AD patients compared to controls. Imaging‐cognitive correlation analysis indicated that the CFH of the right prefrontal cortex was marginally positively related to the Montreal Cognitive Assessment score in patients and the Auditory Verbal Learning Test score. Moreover, taking abnormal AI and CFH values as features, support vector machine‐based classification achieved good accuracy, sensitivity, specificity, and area under the curve by leave‐one‐out cross‐validation. Conclusion: This study suggests that individuals with AD have abnormal cerebral specialization and interhemispheric cooperation. This provides new insights for further elucidation of the pathological mechanisms of AD. [ABSTRACT FROM AUTHOR]

• Decreased functional connectivity of the intralaminar and medial thalamus with the precuneus was observed in our patients, highlighting the different functions of each thalamic subdivision and different disease process for each subnucleus. • Our results suggested that dysfunction of the intralaminar and medial thalamus is instrumental in Alzheimer's disease. • Our findings could contribute to advancements in precision medicine, i.e., the fact that there is dysfunction in the functional connectivity of the intralaminar and medial thalamus with the precuneus could be considered in target-based therapy such as repetitive transcranial magnetic stimulation or deep brain stimulation. Alzheimer's disease (AD) is characterized by global cognitive impairment in multiple cognitive domains. Thalamic dysfunction during AD progression has been reported. However, there are limited studies regarding dysfunction in the functional connectivity (FC) of thalamic subdivisions and the relationship between such dysfunction and clinical assessments. This study examined dysfunction in the FC of thalamic subdivisions and determined the relationship between such dysfunction and clinical assessments. Forty-eight patients with AD and 47 matched healthy controls were recruited and assessed with scales for multiple cognitive domains. Group-wise comparisons of FC with thalamic subdivisions as seed points were conducted to identify abnormal cerebral regions. Moreover, correlation analysis was conducted to evaluate the relationship between abnormal FC and cognitive performance. Decreased FC of the intralaminar and medial nuclei with the left precuneus was observed in patients but not in heathy controls. The abnormal FC of the medial nuclei with the left precuneus was correlated with the Mini Mental State Examination score in the patient group. Using the FC values showing between-group differences, the linear support vector machine classifier achieved quite good in accuracy, sensitivity, specificity and area under the curve. Dysfunction in the FC of the intralaminar and medial thalamus with the precuneus may comprise a potential neural substrate for cognitive impairment during AD progression, which in turn may provide new treatment targets. [ABSTRACT FROM AUTHOR]