An increasing population of dementia patients produces substantial societal impacts. We assessed the prevalence of mild cognitive impairment (MCI) and all-cause dementia, including very mild dementia ...(VMD), in Taiwan. In a nationwide population-based cross-sectional survey, participants were selected by computerized random sampling from all 19 Taiwan counties and were enrolled between December 2011 and March 2013. Cases were identified through in-person interviews based on the National Institute on Aging-Alzheimer's Association clinical criteria. Demographic data and histories involving mental status and function in daily living were collected. The principal objective assessments were the Taiwanese Mental Status Examination and Clinical Dementia Rating. In all, 10,432 people aged 65 years or older (mean age 76.2 ± 6.7, 52.3% women) were interviewed. The age-adjusted prevalence of all-cause dementia was 8.04% (95% CI 7.47-8.61), including a 3.25% (95% CI 2.89-3.61) prevalence of VMD; that of MCI was 18.76% (95% CI 17.91-19.61). Women had a higher prevalence than men of both all-cause dementia (9.71% vs. 6.36%) and MCI (21.63% vs. 15.57%). MCI affects a considerable portion of the population aged 65 and above in Taiwan. The inclusion of VMD yields dementia prevalence rates higher than those previously reported from Taiwan. Old age, female gender, and a low educational level are significant associated factors.
Recent research on Alzheimer's disease (AD) has shown that the decline of cognitive and memory functions is accompanied by a disrupted neuronal connectivity characterized by white matter (WM) ...degeneration. However, changes in the topological organization of WM structural network in AD remain largely unknown. Here, we used diffusion tensor image tractography to construct the human brain WM networks of 25 AD patients and 30 age- and sex-matched healthy controls, followed by a graph theoretical analysis. We found that both AD patients and controls had a small-world topology in WM network, suggesting an optimal balance between structurally segregated and integrative organization. More important, the AD patients exhibited increased shortest path length and decreased global efficiency in WM network compared with controls, implying abnormal topological organization. Furthermore, we showed that the WM network contained highly connected hub regions that were predominately located in the precuneus, cingulate cortex, and dorsolateral prefrontal cortex, which was consistent with the previous diffusion-MRI studies. Specifically, AD patients were found to have reduced nodal efficiency predominantly located in the frontal regions. Finally, we showed that the alterations of various network properties were significantly correlated with the behavior performances. Together, the present study demonstrated for the first time that the Alzheimer's brain was associated with disrupted topological organization in the large-scale WM structural networks, thus providing the structural evidence for abnormalities of systematic integrity in this disease. This work could also have implications for understanding how the abnormalities of structural connectivity in AD underlie behavioral deficits in the patients.
Comorbid medical diseases are highly prevalent in the geriatric population, imposing hardship on healthcare services for demented individuals. Dementia also complicates clinical care for other ...co-existing medical conditions. This study investigated the comorbidities associated with dementia in the elderly population aged 65 years and over in Taiwan.
We conducted a nationwide, population-based, cross-sectional survey; participants were selected by computerized random sampling from all 19 Taiwan counties between December 2011 and March 2013. After exclusion of incomplete or erroneous data, 8,456 subjects were enrolled. Of them, 6,183 were cognitively normal (control group), 1,576 had mild cognitive impairment (MCI), and 697 had dementia. We collected information about types of comorbidities (i.e., vascular risk factors, lung diseases, liver diseases, gastrointestinal diseases, and cancers), Charlson comorbidity index score, and demographic variables to compare subjects with normal cognition, MCI, and dementia.
Regardless of the cognitive condition, over 60% of the individuals in each group had at least one comorbid disease. The proportion of subjects possessing at least three comorbidities was higher in those with cognitive impairment (MCI 20.9%, dementia 27.3%) than in control group (15%). Hypertension and diabetes mellitus were the most common comorbidities. The mean number of comorbidities and Charlson comorbidity index score were greater in MCI and dementia groups than in control group. Logistic regression demonstrated that the comorbidities significantly associated with MCI and dementia were cerebrovascular disease (OR 3.35, CI 2.62-4.28), cirrhosis (OR 3.29, CI 1.29-8.41), asthma (OR 1.56, CI 1.07-2.27), and diabetes mellitus (OR 1.24, CI 1.07-1.44).
Multiple medical comorbid diseases are common in older adults, especially in those with cognitive impairment. Cerebrovascular disease, cirrhosis, asthma, and diabetes mellitus are important contributors to cognitive deterioration in the elderly. Efforts to lower cumulative medical burden in the geriatric population may benefit cognitive function.
The cross‐sectional identification of subjective cognitive decline (SCD) in cognitively normal adults is particularly important for the early effective prevention or intervention of the future ...development of mild cognitive impairments (MCI) or Alzheimer's disease (AD). A pre‐attentive neurophysiological signal that reflects the brain's ability to detect the changes of the environment is called mismatch negativity (MMN) or its magnetic counterpart (MMNm). It has been shown that patients with MCI or AD demonstrate reduced MMN/MMNm responses, while the exact profile of MMN/MMNm in SCD is substantially unknown. We applied magnetoencephalographic recordings to interrogate MMNm activities in healthy controls (HC, n = 29) and individuals with SCD (n = 26). Furthermore, we analyzed gray matter (GM) volumes in the MMNm‐related regions through voxel‐based morphometry and performed apolipoprotein E4 (APOE4) genotyping for all the participants. Our results showed that there were no significant differences in GM volume and proportions of APOE4 carriers between HC and SCD groups. However, individuals with SCD exhibited weakened z‐corrected MMNm responses in the left inferior parietal lobule and right inferior frontal gyrus (IFG) as compared to HC. Based on the regions showing significant between‐group differences, z‐corrected MMNm amplitudes of the right IFG significantly correlated with the memory performance among the SCD participants. Our data suggest that neurophysiological changes of the brain, as indexed by MMNm, precede structural atrophy in the individuals with SCD compared to those without SCD.
This is the first study systematically investigating the magnetic mismatch negativity (MMNm) in individuals with and without subjective cognitive decline (SCD). We found that despite no structural atrophy, individuals with SCD showed reduced MMNm amplitudes particularly in the right inferior frontal gyrus compared to those without SCD. Our data suggest that self‐reported cognitive worsening is a reflection of objective alterations in brain function, which precedes gray matter atrophy.
Subjective memory complaint (SMC), a self‐perceived worsening in memory capacity concurrent with normal performance on standardized cognitive assessments, is considered a risk factor for the ...development of Alzheimer's disease (AD). Deficient sensory gating (SG), referring to the lack of automatic inhibition of neural responses to the second identical stimulus, has been documented in prodromal and incident AD patients. However, it remains unknown whether the cognitively normal elderly with SMC demonstrate alterations of SG function compared with those without SMC. A total of 19 healthy controls (HC) and 16 SMC subjects were included in the present study. Neural responses to the auditory paired‐stimulus paradigm were recorded by the magnetoencephalography and analyzed by the distributed source imaging method of minimum norm estimate. The SG of M50 and M100 components were measured using the amplitude ratio of the second response over the first response at the cortical level. Compared to HC, subjects with SMC showed significantly increased M50 SG ratios in the inferior parietal lobule (IPL). Furthermore, M50 SG ratios in the right IPL yielded an acceptable discriminative ability to distinguish SMC from HC. However, we did not find a significant association between SG ratios and cognitive function requiring inhibitory control either in the HC or SMC group. In conclusion, although SMC subjects have intact cognitive functioning revealed by objective neuropsychological tests, their deficits in automatic inhibitory function could be detected through neurophysiological recordings. Our results suggest that altered brain function occurs in SMC prior to the obvious decline of cognitive performance.
Sensory gating (SG) ratios of auditory M50 and M100 components between healthy control (HC) and subjective memory complaint (SMC) groups were compared in the bilateral superior temporal gyrus (STG), middle temporal gyrus (MTG), inferior frontal gyrus (IFG), and inferior parietal lobule (IPL). The results showed that individuals with SMC demonstrated significantly higher M50 SG ratios (i.e., worse inhibitory function) in the IPL compared to HC.
Levels of amyloid-β (Aβ) and tau peptides in brain have been associated with Alzheimer disease (AD). The current study investigated the abilities of plasma Aβ42 and total-tau (t-tau) levels in ...predicting cognitive decline in subjects with amnestic mild cognitive impairment (MCI). Plasma Aβ42 and t-tau levels were quantified in 22 participants with amnestic MCI through immunomagnetic reduction (IMR) assay at baseline. The cognitive performance of participants was measured through neuropsychological tests at baseline and annual follow-up (average follow-up period of 1.5 years). The predictive value of plasma Aβ42 and t-tau for cognitive status was evaluated. We found that higher levels of Aβ42 and t-tau are associated with lower episodic verbal memory performance at baseline and cognitive decline over the course of follow-up. While Aβ42 or t-tau alone had moderate-to-high discriminatory value in the identification of future cognitive decline, the product of Aβ42 and t-tau offered greater differential value. These preliminary results might suggest that high levels of plasma Aβ42 and t-tau in amnestic MCI are associated with later cognitive decline. A further replication with a larger sample over a longer time period to validate and determine their long-term predictive value is warranted.
Assessing dementia conversion in patients with mild cognitive impairment (MCI) remains challenging owing to pathological heterogeneity. While many MCI patients ultimately proceed to Alzheimer's ...disease (AD), a subset of patients remain stable for various times. Our aim was to characterize the plasma metabolites of nineteen MCI patients proceeding to AD (P-MCI) and twenty-nine stable MCI (S-MCI) patients by untargeted metabolomics profiling. Alterations in the plasma metabolites between the P-MCI and S-MCI groups, as well as between the P-MCI and AD groups, were compared over the observation period. With the help of machine learning-based stratification, a 20-metabolite signature panel was identified that was associated with the presence and progression of AD. Furthermore, when the metabolic signature panel was used for classification of the three patient groups, this gave an accuracy of 73.5% using the panel. Moreover, when specifically classifying the P-MCI and S-MCI subjects, a fivefold cross-validation accuracy of 80.3% was obtained using the random forest model. Importantly, indole-3-propionic acid, a bacteria-generated metabolite from tryptophan, was identified as a predictor of AD progression, suggesting a role for gut microbiota in AD pathophysiology. Our study establishes a metabolite panel to assist in the stratification of MCI patients and to predict conversion to AD.
In mammals, microRNAs can be actively secreted from cells to blood. miR‐29b‐3p has been shown to play a pivotal role in muscle atrophy, but its role in intercellular communication is largely unknown. ...Here, we showed that miR‐29b‐3p was upregulated in normal and premature aging mouse muscle and plasma. miR‐29b‐3p was also upregulated in the blood of aging individuals, and circulating levels of miR‐29b‐3p were negatively correlated with relative appendicular skeletal muscle. Consistently, miR‐29b‐3p was observed in exosomes isolated from long‐term differentiated atrophic C2C12 cells. When C2C12‐derived miR‐29b‐3p‐containing exosomes were uptaken by neuronal SH‐SY5Y cells, increased miR‐29b‐3p levels in recipient cells were observed. Moreover, miR‐29b‐3p overexpression led to downregulation of neuronal‐related genes and inhibition of neuronal differentiation. Interestingly, we identified HIF1α‐AS2 as a novel c‐FOS targeting lncRNA that is induced by miR‐29b‐3p through down‐modulation of c‐FOS and is required for miR‐29b‐3p‐mediated neuronal differentiation inhibition. Our results suggest that atrophy‐associated circulating miR‐29b‐3p may mediate distal communication between muscle cells and neurons.
miR‐29b‐3p‐containing exosomes released from atrophied muscle can be transported via the circulation and transferred to neuronal cells. Increased miR‐29b‐3p levels in neuronal cells may lead to inhibition of neuronal differentiation.
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