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To examine the association of baseline body mass index (BMI) and BMI change with cognitive impairment among older adults in China. The study included data from the Chinese Longitudinal Healthy Longevity Study, a national community-based prospective cohort study from 2002 to 2018. Baseline BMI and BMI change were available for 12,027 adults aged older than 65 years. Cognitive impairment was defined as Chinese version of the Mini Mental State Examination score lower than 18. Multivariable Cox proportional hazard model was used. Among 12,027 participants (mean age was 81.23 years old and 47.48% were male), the proportion of underweight, normal, overweight and obese at baseline was 33.87%, 51.39%, 11.39% and 3.34%, respectively. During an average of 5.9 years' follow-up, 3086 participants (4.35 per 100 person-years) with incident cognitive impairment were identified. Compared with normal weight group, adjusted hazard ratio (AHR) for cognitive impairment was 0.86 (95% CI 0.75-0.99) among overweight group, whereas corresponding AHR was 1.02 (95% CI 0.94-1.10) in underweight and 1.01 (95% CI 0.80-1.28) in obese participants. Large weight loss (< -10%) was significantly associated with an increased risk of cognitive impairment (AHR, 1.42, 95% CI 1.29-1.56), compared to stable weight status group (-5% ~ 5%). In the restricted cubic spline models, BMI change showed a reverse J-shaped association with cognitive impairment. BMI-defined overweight, but not obesity, was associated with a lower risk of cognitive impairment among elderly Chinese adults, while large weight loss was associated with an increased risk. These findings are consistent with weight loss in the prodromal phase of dementia., (© 2021. Springer Nature B.V.)

The apolipoprotein E ε4 (APOE ε4) allele is a well-established genetic risk factor for Alzheimer's disease (AD). Numerous studies have suggested that the modulation of APOE ε4 affects cognition and brain structure and function in healthy populations, particularly in the hippocampus, a key area associated with AD pathology. However, the effect of APOE ε4 allele on cognitive performance, hippocampal structural morphology, and specifically on functional characteristics in patients with AD remains poorly understood. Here, we employed a neuropsychological battery test and multi-modal structural MRI and resting-state functional MRI dataset to systematically investigate cognitive performance, hippocampal structural volume, and functional properties (including local low-frequency oscillating amplitude, intra-regional functional synchrony, and inter-regional functional connectivity) in 16 APOE ε4-carriers and 26 non-carriers at early stages of AD. Compared to non-carriers, APOE ε4-carriers exhibited poorer performance on recognition performance, but performed better on the late item generation of the verbal fluency task (associated with executive function). Structural imaging analysis revealed that APOE ε4-carriers exhibited smaller left hippocampal volumes compared to non-carriers, and the result remains significant after correcting for effects of brain size. Functional imaging analysis revealed that APOE ε4-carriers exhibited decreased amplitude of low-frequency fluctuations in the left hippocampus, non-significant changes in intra-regional synchronization within the hippocampus and decreased hippocampal functional connectivity predominantly in components of the default-mode network including the medial frontal and parietal cortices and the lateral temporal cortical regions. Taken together, our results showed APOE genotypic effects on the cognitive profile and hippocampal structural and functional characteristics in patients at early stages of AD, thus providing empirical evidence for the modulation of the APOE genotype on disease phenotype.

Regional differences in tissue volume and perfusion in brains of individuals with mild cognitive impairment (MCI) versus normal healthy age-matched controls (NC), and the differences between MCI-AD converters and stable MCI patients were investigated. MRI and SPECT scans were performed on 13 MCI (74+6 years) and 12 NC (75+4 years). Of the MCI patients, 10 were followed for up to three years and 4 subsequently converted to Alzheimer's disease (AD). Episodic memory function was assessed using tests of delayed recall for word lists and stories. The volume reductions and hypoperfusion were mainly confined to the medial temporal lobe (MTL) of MCI patients and associated with worse scores on memory tests. Perfusion in the corpus callosum and the gray matter of frontal, lateral temporal, parietal or occipital lobe was not significantly affected in MCI. The 4 MCI-AD converters had relatively low MTL structural volume and perfusion compared to their stable peers.

Purpose: To prospectively evaluate regional alterations in the apparent diffusion coefficient (ADC) of cortical gray and white matter and subcortical structures that are known to be involved in mild cognitive impairment (MCI)., Materials and Methods: Magnetic resonance (MR) imaging was performed in 13 patients with MCI (nine men, four women; mean age, 74 years +/- 6 [standard deviation]) and 13 healthy elderly control subjects (seven men, six women; mean age, 75 years +/- 4). This study was approved by the institutional review board and was HIPAA compliant. Each subject gave informed consent. ADC was measured from manually drawn regions of interest (ROIs) of the hippocampus, parahippocampal gyrus, amygdala, corpus callosum, and anterior and posterior cingulate gyrus and from automatically defined frontal, parietal, occipital, and temporal lobes by using template masking. ROIs were outlined on anatomic images then mapped onto ADC maps by using coregistration transformation matrix. A skeleton-based region competition segmentation algorithm was used for segmentation of gray and white matter. The group difference in ADC values was assessed with independent-sample t tests. Pearson correlation analysis was used to examine the correlation of ADC values with age and memory test scores., Results: Higher ADCs were found in hippocampus, temporal lobe gray matter, and corpus callosum of patients with MCI compared with that of control subjects (P < .05). By pooling all subjects together, an elevated hippocampal ADC was significantly correlated with worse memory performance scores in 5-minute and 30-minute delayed word-list recall tasks (P < .05)., Conclusion: ADCs from gray and white matter of different brain regions can be analyzed by applying an automated template-masking method in conjunction with a skeleton-based region competition segmentation algorithm., ((c) RSNA, 2006.)

Background/aims: A quantitative method was applied to measure the volume of white matter hyperintensity (WMH) in different brain regions of subjects with Alzheimer's disease (AD), mild cognitive impairment (MCI) and normal healthy age-matched controls, and the relationship between regional WMH and age and cognitive function was investigated., Methods: Fifty-six subjects were included in this study, 27 AD, 15 MCI and 14 normal age-matched controls. A user-friendly software was developed for WMH quantification in frontal, temporal, and parieto-occipital lobes. Mini-Mental State Examination and cognitive scores in performing naming, language fluency, and memory tasks were obtained for correlation analysis., Results: AD patients had the greatest total WMH volume, followed by MCI, then controls. However, there was a large variation within each group, and the difference did not reach a significant level. There was a positive linear correlation between the total WMH (p = 0.031) and the frontal WMH (p = 0.006) vs. age. After age correction the Boston Naming Test scores were negatively correlated with the total WMH volume in the AD (p = 0.03) and the control (p = 0.03) groups, and with the frontal WMH in controls (p = 0.01)., Conclusion: We demonstrated a quantitative analysis method to measure regional WMH. Although WMH was not strongly associated with disease severity or cognition, it may provide a characteristic neuroimaging parameter in the study of AD development., (Copyright (c) 2006 S. Karger AG, Basel.)

Background: Corpus callosum atrophy possibly indicates neuronal degeneration in association cortex in Alzheimer's disease (AD). Water diffusivity allows detecting physiological changes that probably occur earlier than structural shrinkage in cerebral regions during the development of AD., Objective: To simultaneously investigate the focal volumetric and early structural changes with apparent diffusion coefficient (ADC) of corpus callosum in mild cognitive impairment (MCI), and to explore the regional pattern of ADC increase in hippocampus and corpus callosum., Methods: Thirteen subjects with MCI and 13 healthy age-matched control subjects were studied. With three-dimensional volumetric spoiled gradient recalled echo MRI images, we measured the volume of hippocampus and corpus callosum. Using MRI-guided diffusion-weighted imaging analysis, we calculated ADCs from hippocampus and corpus callosum. Within the receiver-operation curve (ROC) statistical framework, areas under ROC curves from hippocampal and callosal ADCs were compared in differentiating between MCI and controls., Results: After normalization to intracranial volume, hippocampal, not callosal, volume was significantly reduced in MCI. ADC values were increased in hippocampus and corpus callosum in MCI. The extent of ADC increase was similar between hippocampus and corpus callosum., Conclusion: Alterations in water diffusivity may precede corpus callosum atrophy during the development of MCI. Diffusion changes might occur simultaneously in allocortex and neocortex in MCI., (Copyright (c) 2006 S. Karger AG, Basel)

There exists controversy on the MR T(2) relaxometry of hippocampus in Alzheimer's disease (AD). The aim of our study was to examine whether there was a prolonged T(2) relaxation time (T(2)) in hippocampus and amygdala in AD, and whether in AD, the relaxometry data correlated to cognitive performance. In a 1.5 T MR scanner, T(2) of hippocampus and amygdala was measured from 51 patients with AD, 23 subjects with vascular dementia (VaD) and 31 healthy elderly controls. The cognitive performance was assessed with the Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog). The AD patients had longer T(2) in hippocampus and amygdala than VaD subjects and healthy elderly controls. In AD, the right hippocampal T(2) was correlated with ADAS-Cog scores, whereas amygdaloid T(2) was not.

Background: Naturally occurring antibodies (NAbs) are germline-encoded immunoglobulins that can bind to and clear out self-neo-epitopes as well as apoptotic and necrotic cells. However, NAbs pathological relevance in Alzheimer's disease (AD) is not well-understood. Methods: Twenty-eight candidate proteins encoded by AD-associated genes were selected for this study based on a number of selection criteria, including preferential expression in the brain and B-lymphocyte cells. The levels of NAbs in plasma were analyzed according to their epitopes in age- and gender-matched cognitively normal subjects (CN, n = 56), subjects with mild cognitive impairment (MCI, n = 16) and subjects with AD (n = 56). We aimed to study the levels of their NAbs in plasma and their associations with cognitive decline in individuals with AD. Results: Of the 28 antigens tested, 17 showed decreased NAbs in individuals with AD; in particular, NAb-TREM2 had an area under the ROC curve of 0.806, with the highest sensitivity (0.370) at 95% specificity among all 28 tests. Further protein–protein interaction networks and functional enrichment analysis suggested that target genes were enriched in AD-related pathological processes classified under "Alzheimer's disease", "neurodegenerative disease" and "amyloidosis". The "Alzheimer's disease" and "neurodegenerative disease" clusters, which converged on the initial "recognition" step of microglial phagocytosis, showed the best diagnostic performance for AD. Conclusions: This study suggests a decline in the function of the adaptive immune system in AD, and the levels of circulating NAbs are likely to serve as biomarkers for surveilling the progression of AD. [ABSTRACT FROM AUTHOR]

With population ageing worldwide, dementia poses one of the greatest global challenges for health and social care in the 21st century. In 2019, around 55 million people were affected by dementia, with the majority living in low- and middle-income countries. Dementia leads to increased costs for governments, communities, families and individuals. Dementia is overwhelming for the family and caregivers of the person with dementia, who are the cornerstone of care and support systems throughout the world. To assist countries in addressing the global burden of dementia, the World Health Organisation (WHO) developed the Global Action Plan on the Public Health Response to Dementia 2017–2025. It proposes actions to be taken by governments, civil society, and other global and regional partners across seven action areas, one of which is dementia risk reduction. This paper is based on WHO Guidelines on risk reduction of cognitive decline and dementia and presents recommendations on evidence-based, multisectoral interventions for reducing dementia risks, considerations for their implementation and policy actions. These global evidence-informed recommendations were developed by WHO, following a rigorous guideline development methodology and involved a panel of academicians and clinicians with multidisciplinary expertise and representing geographical diversity. The recommendations are considered under three broad headings: lifestyle and behaviour interventions, interventions for physical health conditions and specific interventions. By supporting health and social care professionals, particularly by improving their capacity to provide gender and culturally appropriate interventions to the general population, the risk of developing dementia can be potentially reduced, or its progression delayed. [ABSTRACT FROM AUTHOR]

Background: Apathy has been suggested as a potential predictor of mild cognitive impairment (MCI) progression to dementia. Whether it might predict the transition from normal cognitive function to cognitive impairment has been less studied. The current study aimed to provide a comprehensive summary of the evidence on the association between apathy and the transition from normal cognitive function to cognitive impairment. Methods: We searched the PubMed, Embase, and Web of Science databases for longitudinal prospective cohort studies that evaluated apathy at baseline in the cognitively normal population and had cognitive impairment as the outcome. Random effects models were used, and heterogeneity was explored with stratification. The stability of the synthesized result was indicated using sensitivity analysis by excluding one study each time and recalculating the overall effect. Results: Ten studies comprising 26,195 participants were included. Apathy status was available for 22,101 participants. Apathy was present in 1,803 of 22,101 participants (8.16%). Follow-up ranged from 1 to 13 years. The combined odds ratio (OR) of cognitive impairment for patients with apathy was 2.07 (95% CI: 1.43–2.99; I2 = 86%), and the combined hazard ratio was 2.70 (95% CI: 1.38–5.27; I2 = 94%). The OR meta-analyses for different conversion outcomes were MCI (OR = 3.38, 95% CI: 1.57–7.28; I2 =71%), cognitive decline (OR = 1.27, 95% CI: 0.81–2.00; I2 = 64%) and dementia (OR = 2.12, 95% CI: 1.32–3.41; I2 = 86%). Subgroup analysis suggested that the association between apathy and cognitive impairment changed with age, depression adjustments, apathy measurement, and follow-up time. Conclusions: Apathy was associated with a greater than 2-fold increased risk of progression to cognitive impairment in the cognitively normal population. Future interventions targeting apathy management in the general population may reduce the risk of cognitive impairment. [ABSTRACT FROM AUTHOR]

Identifying heterogeneous cognitive impairment markers at an early stage is vital for Alzheimer's disease diagnosis. However, due to complex and uncertain brain connectivity features in the cognitive domains, it remains challenging to quantify functional brain connectomic changes during non-pharmacological interventions for amnestic mild cognitive impairment (aMCI) patients. We present a quantitative method for functional brain network analysis of fMRI data based on the multi-graph unsupervised Gaussian embedding method (MG2G). This neural network-based model can effectively learn low-dimensional Gaussian distributions from the original high-dimensional sparse functional brain networks, quantify uncertainties in link prediction, and discover the intrinsic dimensionality of brain networks. Using the Wasserstein distance to measure probabilistic changes, we discovered that brain regions in the default mode network and somatosensory/somatomotor hand, fronto-parietal task control, memory retrieval, and visual and dorsal attention systems had relatively large variations during non-pharmacological training, which might provide distinct biomarkers for fine-grained monitoring of aMCI cognitive alteration. An important finding of our study is the ability of the new method to capture subtle changes for individual patients before and after short-term intervention. More broadly, the MG2G method can be used in studying multiple brain disorders and injuries, e.g., in Parkinson's disease or traumatic brain injury (TBI), and hence it will be useful to the wider neuroscience community. Author summary: There is still no cure and no effective drug treatment for Alzheimer's disease (AD). Hence, non-pharmacological cognitive intervention for patients at early stages of AD has received a lot of attention due to its non-invasive manner, safety, and scalability. Multi-domain interventions targeting memory and non-memory domains simultaneously are urgently needed for an optimal intervention effect on amnestic mild cognitive impairment (aMCI) patients. However, most of the previous multi-domain cognitive intervention studies evaluated the intervention outcomes based solely on neuropsychological assessment or simple characterization of brain anatomical structural changes. This work is the first of its kind to develop a patient-specific quantitative analysis for the underlying functional brain regional activity changes during the multi-domain cognitive intervention process. Specifically, we used fMRI data from 12 patients, who were trained for three months, and we developed the multi-graph unsupervised Gaussian embedding method (MG2G) to analyze these data. We obtained probabilistic changes across all the brain regions, and we found that brain regions in the default mode network and somatosensory/somatomotor hand, fronto-parietal task control, memory retrieval, and visual and dorsal attention systems had relatively large variations during the non-pharmacological training. These fundamental insights could provide effective new biomarkers for monitoring of aMCI cognitive alteration. [ABSTRACT FROM AUTHOR]

Rationale and objective: Vortioxetine has been reported to exhibit a variety of neurobiological functions and neuroprotective effects. In the present study, we aimed to investigate the effects of vortioxetine on cognitive performance in a transgenic mouse model of Alzheimer's disease (AD). Methods: We administered vortioxetine (10 mg/kg, i.p., every day, for approximately 6 weeks), which acts on multiple 5-serotonin (5-HT) receptors, to 3.5-month-old 5×FAD mice. Subsequently, we used the open field (OF) test to detect anxiety-like behavior in the mice. The novel object recognition (NOR) test and Morris water maze (MWM) were used to assess the cognitive states of the 5×FAD mice. We also measured the levels of insoluble amyloid plaques and soluble β-amyloid (Aβ) plaques. Finally, we explored the expression levels of postsynaptic density protein 95 (PSD95), synaptophysin (SYP), and synaptotagmin-1 (SYT1) in the hippocampus of the mice. Results: The administration of vortioxetine effectively reversed the reduction in anxiety-type behaviors in 5×FAD mice and improved the impairment in recognition memory and spatial reference memory. However, we did not find that vortioxetine decreased or delayed the formation of amyloid plaques or Aβ. Interestingly, we found a significant increase in the expression levels of PSD95, SYP, and SYT1 in the 5×FAD mice after vortioxetine treatment compared with the control group. Conclusion: These results demonstrate that vortioxetine may improve cognitive impairment in 5×FAD mice. The role in cognitive improvement may be related to the beneficial effects of vortioxetine on synaptic function. [ABSTRACT FROM AUTHOR]

This study examined the perception of Alzheimer's disease (AD) and caregiving among family caregivers of individuals with mild cognitive impairment (MCI) and AD in China. In-depth semistructured interviews were conducted with 46 family caregivers of individuals with cognitive impairment in 2009 in Wuhan and Beijing, China. Participants included 38 spouses, 7 adult children, and 1 sibling, aged between 41 and 85 years old. The findings showed that all family caregivers thought the Chinese terminology of AD laonian chidai, brought discrimination to individuals with cognitive impairment. Caregivers of individuals with AD experienced burden and desired an increase of formal services. Traditional beliefs of respecting elders and caring for extended family members were held among family caregivers of individuals with cognitive impairment, and there was nearly no difference found between caregivers of AD and those of MCI. It implied that traditional culture provided positive influences on caring for elders with cognitive impairment. An alternative term for MCI may contribute to further reducing the discrimination brought by the old Chinese terminology of AD laonian chidai. Development of formal services for elders with cognitive impairment may contribute to reducing caregivers' worries about future caregiving. [ABSTRACT FROM AUTHOR]

Objectives: The oldest‐old (aged ≥80 years) are the fastest growing population segment and age is related to cognitive impairment. We aimed to estimate the association between cognitive impairment and all‐cause mortality, in addition to the relationship with different cognitive subdomains among the oldest‐old in China. Methods: We analyzed 25,285 participants recruited from 22 out of 30 provinces in the Chinese Longitudinal Healthy Longevity Survey (CLHLS) from 1998 to 2008, with mortality follow‐up until 2014. Cognitive function was measured by the Chinese‐version 30‐item Mini‐Mental State Examination (MMSE), classified as no (MMSE score: 25–30), mild (18–24), moderate (10–17), and severe (0–9) impairment. We used time‐dependent Cox model to evaluate the relationship between time‐varying cognition and mortality. Results: The relationship between cognition and mortality showed a dose–response pattern among the overall population. Compared to those with no impairment, participants with moderate (HR = 1.41, 95% CI 1.28–1.56) and severe (HR = 1.77, 95% CI 1.59–1.96) cognitive impairment showed increased mortality risk. Impairment in the subdomain of orientation was independently associated with increased mortality risk (HR = 1.20, 95% CI 1.05–1.36) among participants without overall cognitive impairment. Urban and rural residents had similar mortality risk. Conclusions: A consistent dose–response pattern existed between cognitive impairment and all‐cause mortality. Orientation was associated with mortality in the population without cognitive impairment. Similar mortality regardless of residence areas indicated scarce health care and treatment for cognitive impairment in China from 1998 to 2014. [ABSTRACT FROM AUTHOR]