<i>Background/Aims:</i> We investigated the clinical and cognitive features of patients with mild general paresis of the insane (GPI) in comparison to Alzheimer’s disease (AD) patients, mild frontotemporal dementia (FTD) patients and normal elderly individuals. <i>Methods:</i> Twelve patients with mild GPI, 24 patients with mild AD, 11 patients with mild FTD and 36 healthy subjects participated in the current study. A comprehensive neuropsychological battery was used to assess memory, language, attention, executive function, visuospatial ability, etc. In addition, cranial MRI were also obtained from the 3 patient groups. <i>Results:</i> Mild GPI showed a similar pattern of cognitive impairments in memory, language and executive function to mild AD, but a mixed pattern of dissimilarities to mild FTD. Mild GPI patients had more complaints and positive signs in the nervous system than mild AD patients, and cranial MRI results showed that mild GPI patients usually had atrophy of the medial temporal lobe. <i>Conclusion:</i> There is an overall decline in cognitive functions of mild GPI patients, which is comparable to that in AD patients, suggesting that there is a wide range of structural changes in the brains of mild GPI patients as well. However, further studies are needed to verify whether these structural changes are similar to those in AD.
Insulin signaling pathway and insulin degrading enzyme have been known to play a role in the pathogenesis of Alzheimer's disease. This study is to get a better understanding of age-related alteration of IDE, insulin signaling and effect of rosiglitazone(RSG). SD rats were divided into 6 groups according to different ages and treatments: 3 months old, 8; 12 months old, 12; 18 months old, 12; 18 months old, RSG 1 mg/kg/d, q.d., 12;18 months old, intrahippocampal bilateral infusion of Aβ42, 12; 18 months old, intrahippocampal infusion of Aβ42, RSG, 12. Cognitive function was evaluated by Morris Water Maze. IDE and pAKT expression were assayed by Western-blot and immunofluorescenct staining. IDE activity was obtained by RIA. Aβ level was assayed by ELISA. Cognition decreased progressively as ageing. 3 m rats had the shortest escape latency in Morris Maze (9.70s), 18 m rats had the longest (27.80). 12 m in between (15.50s). RSG might attenuate the impairment (14.60s) (p < 0.05, vs 18 m rats). In space probing test, the “counts of crossing the platform” decreased by 22.22 %(p < 0.05) for 12 m rats and by 27.78% (p < 0.05) for 18 m rats. RSG raised the counts by 23.08% as comparing with 18 m rats (p < 0.05). IDE and pAKT expression declined with age. The difference between 3 m and 12 m rats was obvious (p < 0.05) while the gap between 3 m and 18 m was more significant, as shown by Western blot and immunofluorescent stain. RSG could rectify the decrement significantly(p < 0.05, vs 18 m rats). IDE activity declined in an age-dependent manner which dropped sharply in 12 m rats (p < 0.01). Chronic administration of RSG could upregulate IDE activity moderately in liver (p < 0.05) and slightly in brain. RSG could also modestly improve cognition in Aβ-induced AD-like rat model, shortening escape latency from 79.40s to 58.51s(by 26.31%, p < 0.05), reducing intracerebral Aβ level from 235.53pmol/L to 187.34pmol/L (by 20.46%,p < 0.05). There existed age-dependent insulin signaling impairment and IDE downregulation during normal ageing, which might be partially responsible for cognitive decline and played a role in the pathogenesis of AD. Rosiglitazone could rectify insulin signaling dysfunction and upregulate IDE thus might have potential therapeutic value for AD.
Abstract INTRODUCTION The LIfestyle for BRAin Health (LIBRA) index yields a dementia risk score based on modifiable lifestyle factors and is validated in Western samples. We investigated whether the association between LIBRA scores and incident dementia is moderated by geographical location or sociodemographic characteristics. METHODS We combined data from 21 prospective cohorts across six continents ( N = 31,680) and conducted cohort‐specific Cox proportional hazard regression analyses in a two‐step individual participant data meta‐analysis. RESULTS A one‐standard‐deviation increase in LIBRA score was associated with a 21% higher risk for dementia. The association was stronger for Asian cohorts compared to European cohorts, and for individuals aged ≤75 years (vs older), though only within the first 5 years of follow‐up. No interactions with sex, education, or socioeconomic position were observed. DISCUSSION Modifiable risk and protective factors appear relevant for dementia risk reduction across diverse geographical and sociodemographic groups. Highlights A two‐step individual participant data meta‐analysis was conducted. This was done at a global scale using data from 21 ethno‐regionally diverse cohorts. The association between a modifiable dementia risk score and dementia was examined. The association was modified by geographical region and age at baseline. Yet, modifiable dementia risk and protective factors appear relevant in all investigated groups and regions.
Objective To identify the sensitivity and specificity of Animal-City Alternating Form Fluency Test (ACFT) differentiating mild cognitive impairment (MCI) and Alzheimer's disease (AD) from normal controls. Methods A total of 121 MCI patients, 104 AD patients and 104 healthy controls, who were matched in sex, age and education level, were enrolled in this study. They performed Animal Category Verbal Fluency Test (AFT), City Category Verbal Fluency Test (CFT) and ACFT. A series of standard neuropsychological tests were also administered to reflect episodic memory, verbal ability, working memory, executive function and processing speed. The validity and related influencing factors of ACFT was evaluated. Results Compared with control group, the ACFT correct number in MCI and AD groups reduced significantly ( P = 0.000, 0.000). Receiver operating characteristic (ROC) curve revealed the sensitivity and specificity of ACFT in discriminating MCI ( P = 0.012, 0.030) and AD ( P = 0.004, 0.003) from normal controls were higher than those of AFT and CFT. There was no correlation of correct number in ACFT with age and education ( P > 0.05, for all). The correlations of ACFT with Stroop Color-Word Test (SCWT), Digital Symbol Substitution Test (DSST), Shape Trail Test (STT) and Digit Span Test (DS), all of which reflected attention and executive function, were significantly closer than those of AFT and CFT ( P < 0.05, for all). Conclusions ACFT is more efficient in early cognitive impairment identification than the other traditional category verbal fluency tests. It is a new variant form of category verbal fluency test that could assess cognitive function and could be broadly applied in clinical practice. DOI: 10.3969/j.issn.1672-6731.2015.07.010
Abstract Tau pathology and its spatial propagation in Alzheimer's disease (AD) play crucial roles in the neurodegenerative cascade leading to dementia. However, the underlying mechanisms linking tau spreading to glucose metabolism remain elusive. To address this, we aimed to examine the association between pathologic tau aggregation, functional connectivity, and cascading glucose metabolism and further explore the underlying interplay mechanisms. In this prospective cohort study, we enrolled 79 participants with 18 F‐Florzolotau positron emission tomography (PET), 18 F‐fluorodeoxyglucose PET, resting‐state functional, and anatomical magnetic resonance imaging (MRI) images in the hospital‐based Shanghai Memory Study. We employed generalized linear regression and correlation analyses to assess the associations between Florzolotau accumulation, functional connectivity, and glucose metabolism in whole‐brain and network‐specific manners. Causal mediation analysis was used to evaluate whether functional connectivity mediates the association between pathologic tau and cascading glucose metabolism. We examined 22 normal controls and 57 patients with AD. In the AD group, functional connectivity was associated with Florzolotau covariance ( β = .837, r = 0.472, p < .001) and glucose covariance ( β = 1.01, r = 0.499, p < .001). Brain regions with higher tau accumulation tend to be connected to other regions with high tau accumulation through functional connectivity or metabolic connectivity. Mediation analyses further suggest that functional connectivity partially modulates the influence of tau accumulation on downstream glucose metabolism (mediation proportion: 49.9%). Pathologic tau may affect functionally connected neurons directly, triggering downstream glucose metabolism changes. This study sheds light on the intricate relationship between tau pathology, functional connectivity, and downstream glucose metabolism, providing critical insights into AD pathophysiology and potential therapeutic targets.
<b><i>Objects:</i></b> Different variations of the Stroop Color-Word Test (SCWT) exist and the tests differ in the number of items on each test card. The optimal number of items per card of the SCWT<b><i></i></b> is unclear. <b><i>Methods:</i></b> A comprehensive neuropsychological battery including the SCWT was administered to 237 cognitively normal controls (NC), 221 patients with mild cognitive impairment (MCI), and 160 patients with Alzheimer’s disease (AD). We compared the accuracy for different items of card C (SCWT-C10<sub>accuracy</sub>, SCWT-C24<sub>accuracy</sub>, and SCWT-C50<sub>accuracy</sub>) in distinguishing patients with MCI and AD from NC. <b><i>Results:</i></b> The correct responses for different items of card C were ranked in the order: NC > MCI > AD group and mild AD > moderate AD, except for SCWT-C24<sub>accuracy</sub>. The validity of SCWT-C24<sub>accuracy</sub> was similar to that of SCWT-C50<sub>accuracy</sub> for discriminating MCI and AD from NC, as well as different levels of AD. <b><i>Conclusion:</i></b> We concluded that the number of items on the accuracy of the response was unrelated to its sensitivity to deficits and we preferred the 24-item version in daily clinical use.
Abstract Background Memory deficits are a hallmark of many different neurological and psychiatric conditions. The Rey-Osterrieth complex figure (ROCF) is the state–of-the-art assessment tool for neuropsychologists across the globe to assess the degree of non-verbal visual memory deterioration. To obtain a score, a trained clinician inspects a patient’s ROCF drawing and quantifies deviations from the original figure. This manual procedure is time-consuming, slow and scores vary depending on the clinician’s experience, motivation and tiredness. Methods Here, we leverage novel deep learning architectures to automatize the rating of memory deficits. For this, we collected more than 20k hand-drawn ROCF drawings from patients with various neurological and psychiatric disorders as well as healthy participants. Unbiased ground truth ROCF scores were obtained from crowdsourced human intelligence. This dataset was used to train and evaluate a multi-head convolutional neural network. Results The model performs highly unbiased as it yielded predictions very close to the ground truth and the error was similarly distributed around zero. The neural network outperforms both online raters and clinicians. The scoring system can reliably identify and accurately score individual figure elements in previously unseen ROCF drawings, which facilitates explainability of the AI-scoring system. To ensure generalizability and clinical utility, the model performance was successfully replicated in a large independent prospective validation study that was pre-registered prior to data collection. Conclusions Our AI-powered scoring system provides healthcare institutions worldwide with a digital tool to assess objectively, reliably and time-efficiently the performance in the ROCF test from hand-drawn images.
Abstract Background The blood-based biomarkers are approaching the clinical practice of Alzheimer’s disease (AD). Chronic kidney disease (CKD) has a potential confounding effect on peripheral protein levels. It is essential to characterize the impact of renal function on AD markers. Methods Plasma phospho-tau181 (P-tau181), and neurofilament light (NfL) were assayed via the Simoa HD-X platform in 1189 dementia-free participants from the Shanghai Aging Study (SAS). The estimated glomerular filter rate (eGFR) was calculated. The association between renal function and blood NfL, P-tau181 was analyzed. An analysis of interactions between various demographic and comorbid factors and eGFR was conducted. Results The eGFR levels were negatively associated with plasma concentrations of NfL and P-tau181 (B = -0.19, 95%CI -0.224 to -0.156, P < 0.001; B = -0.009, 95%CI -0.013 to -0.005, P < 0.001, respectively). After adjusting for demographic characteristics and comorbid diseases, eGFR remained significantly correlated with plasma NfL (B = -0.010, 95%CI -0.133 to -0.068, P < 0.001), but not with P-tau181 (B = -0.003, 95%CI -0.007 to 0.001, P = 0.194). A significant interaction between age and eGFR was found for plasma NfL (P interaction < 0.001). In participants ≥ 70 years and with eGFR < 60 ml/min/1.73 m 2 , the correlation between eGFR and plasma NfL was significantly remarkable (B = -0.790, 95%CI -1.026 to -0,554, P < 0.001). Conclusions Considering renal function and age is crucial when interpreting AD biomarkers in the general aging population.
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