Cerebellar gray matter and white matter damage among older adults with prediabetes.

AIMS: To investigate alterations in cerebrum and cerebellum in prediabetes. Cerebellar injury in diabetes is traceable, but it has not been systematically studied, and whether cerebellar injury occurs and the degree of damage in prediabetes are not known. METHODS: The current study investigated cerebral and cerebellar gray matter volume, white matter volume, white matter microstructure and white matter hyperintensity on T1-weighted, T2-weighted fluid-attenuated inversion recovery and diffusion tensor imaging scans in 78 individuals with normal glucose metabolism, 92 with prediabetes, and 108 with type 2 diabetes. RESULTS: Participants with prediabetes showed significant gray matter and white matter atrophy, microstructural damage in the cerebellar and cerebral regions. Additionally, widespread structural alterations were observed in the diabetic stage. The function of the damaged brain area was further decoded in Neurosynth, and the damaged cerebellar area with prediabetic lesions was closely related to motor function, while the area affected by diabetes was related to complex cognitive function in addition to motor function. CONCLUSIONS: Cerebellar injury had already appeared in the prediabetic stage, and cerebellar injury was aggravated in the diabetic stage; therefore, the cerebellum is a key area that is damaged early in the development of diabetes.

Leisure activities as reserve mediators of the relationship between loneliness and cognition in aging.

Previous studies have found that loneliness affects cognitive functions in older persons. However, the influence of loneliness on different cognitive fields and the internal mechanism of the relationship are unclear. A total of 4772 older persons aged above 50 years (Mean = 65.31, SD = 6.96, 57.7% female) were included in this study. All the participants completed the characteristics scale, as well as the loneliness scale, leisure activity scale, and cognitive function tests in six domains. The results showed that 17.6% of participants had high loneliness, while 16.7% of participants had low loneliness. Associations were observed between higher levels of loneliness and lower scores in general cognitive ability, memory, and executive functions. Mediation analysis suggested that leisure activities, encompassing mental, physical, and social activities, were associated with cognitive functions in the context of loneliness. These results indicate that leisure activities may play a significant role in the relationship between loneliness and cognitive functions in older adults. The study highlights the importance of considering leisure activities in this demographic to potentially mitigate the adverse cognitive effects associated with loneliness.

Divergent brain regional atrophy and associated fiber disruption in amnestic and non-amnestic MCI.

BACKGROUND: Understanding the pathological characteristics of various mild cognitive impairment (MCI) subtypes is crucial for the differential diagnosis of dementia. The purpose of this study was to feature divergent symptom-deficit profiles in amnestic MCI (aMCI) and non-amnestic MCI (naMCI). METHODS: T1 and DTI MRI data from a total of 158 older adults with 50 normal controls, 56 aMCI, and 52 naMCI were included. The voxel-wise gray matter volumes and the number of seed-based white matter fiber bundles were compared among these three groups. Furthermore, correlation and mediation analyses between the neuroimaging indices and cognitive measures were performed. RESULTS: The aMCI with specific memory abnormalities was characterized by volumetric atrophy of the left hippocampus but not by damage in the linked white matter fiber bundles. Conversely, naMCI was characterized by both the altered volume of the right inferior frontal gyrus and the significant damage to fiber bundles traversing the region in all three directions, not only affecting fibers around the atrophied area but also distant fibers. Mediation analyses of gray matter-white matter-cognition showed that gray matter atrophy affects the number of fiber bundles and further affects attention and executive function. Meanwhile, fiber bundle damage also affects gray matter volume, which further affects visual processing and language. CONCLUSIONS: The divergent structural damage patterns of the MCI subtypes and cognitive dysfunctions highlight the importance of detailed differential diagnoses in the early stages of pathological neurodegenerative diseases to deepen the understanding of dementia subtypes and inform targeted early clinical interventions.

Multi-domain cognition dysfunction accompanies frontoparietal and temporal amyloid accumulation in the elderly.

It is helpful to understand the pathology of Alzheimer's disease by exploring the relationship between amyloid-ß accumulation and cognition. The study explored the relationship between regional amyloid-ß accumulation and multiple cognitions and study their application value in the Alzheimer's disease diagnosis. 135 participants completed 18F-florbetapir Positron Emission Tomography (PET), structural MRI, and a cognitive battery. Partial correlation was used to examine the relationship between global and regional amyloid-ß accumulation and cognitions. Then, a support vector machine was applied to determine whether cognition-related accumulation regions can adequately distinguish the cognitively normal controls (76 participants) and mild cognitive impairment (30 participants) groups or mild cognitive impairment and Alzheimer's disease (29 participants) groups. The result showed that amyloid-ß accumulation regions were mainly located in the frontoparietal cortex, calcarine fissure, and surrounding cortex and temporal pole regions. Episodic memory-related regions included the frontoparietal cortices; executive function-related regions included the frontoparietal, temporal, and occipital cortices; and processing speed-related regions included the frontal and occipital cortices. Support vector machine analysis showed that only episodic memory-related amyloid-ß accumulation regions had better classification performance during the progression of Alzheimer's disease. Assessing regional changes in amyloid, particularly in frontoparietal regions, can aid in the early detection of amyloid-related decline in cognitive function.

The Aging Patterns of Brain Structure, Function, and Energy Metabolism.

The normal aging process brings changes in brain structure, function, and energy metabolism, which are presumed to contribute to the age-related decline in brain function and cognitive ability. This chapter aims to summarize the aging patterns of brain structure, function, and energy metabolism to distinguish them from the pathological changes associated with neurodegenerative diseases and explore protective factors in aging. We first described the normal atrophy pattern of cortical gray matter with age, which is negatively affected by some neurodegenerative diseases and is protected by a healthy lifestyle, such as physical exercise. Next, we summarized the main types of age-related white matter lesions, including white matter atrophy and hyperintensity. Age-related white matter changes mainly occurred in the frontal lobe, and white matter lesions in posterior regions may be an early sign of Alzheimer's disease. In addition, the relationship between brain activity and various cognitive functions during aging was discussed based on electroencephalography, magnetoencephalogram, and functional magnetic resonance imaging. An age-related reduction in occipital activity is coupled with increased frontal activity, which supports the posterior-anterior shift in aging (PASA) theory. Finally, we discussed the relationship between amyloid-ß deposition and tau accumulation in the brain, as pathological manifestations of neurodegenerative disease and aging.

Naoxin'an capsules protect brain function and structure in patients with vascular cognitive impairment.

Introduction: Vascular cognitive impairment (VCI) is one of the most common types of dementia. Naoxin'an capsule (NXA), a traditional Chinese medicine compound, has been used to treat VCI for a long time in the clinic. Previous studies proved that the NXA capsules could ameliorate the cerebral mitochondrion deficits of VCI animals. This study aimed to investigate the protectiveness of NXA on human brain structure and function in patients with VCI. Methods: In total, 100 VCI patients were enrolled in this 24-week trial and randomly divided into the NXA capsules group (n = 50) and the ginkgo biloba capsules control group (n = 50). Before and after the treatment, cognitive behavior tests and multimodal brain magnetic resonance imaging were analyzed to comprehensively evaluate the effectiveness of NXA treatment on VCI patients after 24 weeks. Results: We found that the NXA group significantly improved overall cognitive ability (Alzheimer's Disease Assessment Scale-Cognitive section, p = 0.001; Mini-Mental Status Examination, p = 0.003), memory (Rey-Osterrieth Complex Figure test, p < 0.001) and executive function (Trail Making Test-A, p = 0.024) performance after treatment compared with the control group. For brain function, the degree of centrality in the left middle frontal gyrus, right postcentral gyrus, and left supplementary motor area increased in the NXA group and decreased in the ginkgo biloba group after treatment. The fractional amplitude of low-frequency fluctuation (fALFF) of the left precentral and right superior parietal gyrus increased, and the fALFF of the right parahippocampal and left inferior temporal gyrus decreased in the NXA group after treatment. For brain structure, the gray matter density of the left postcentral gyrus increased in the NXA group after treatment, and the total volume of white matter hyperintensity showed a decreasing trend but was not statistically significant. Furthermore, the improvement effect of NXA on executive function was associated with changes in brain function. Conclusion: These findings suggest that the NXA capsules improved cognitive performance and multiregional brain function, as well as gray matter structure in the postcentral gyrus.

Hippocampus-centred grey matter covariance networks predict the development and reversion of mild cognitive impairment.

BACKGROUND: Mild cognitive impairment (MCI) has been thought of as the transitional stage between normal ageing and Alzheimer's disease, involving substantial changes in brain grey matter structures. As most previous studies have focused on single regions (e.g. the hippocampus) and their changes during MCI development and reversion, the relationship between grey matter covariance among distributed brain regions and clinical development and reversion of MCI remains unclear. METHODS: With samples from two independent studies (155 from the Beijing Aging Brain Rejuvenation Initiative and 286 from the Alzheimer's Disease Neuroimaging Initiative), grey matter covariance of default, frontoparietal, and hippocampal networks were identified by seed-based partial least square analyses, and random forest models were applied to predict the progression from normal cognition to MCI (N-t-M) and the reversion from MCI to normal cognition (M-t-N). RESULTS: With varying degrees, the grey matter covariance in the three networks could predict N-t-M progression (AUC = 0.692-0.792) and M-t-N reversion (AUC = 0.701-0.809). Further analyses indicated that the hippocampus has emerged as an important region in reversion prediction within all three brain networks, and even though the hippocampus itself could predict the clinical reversion of M-t-N, the grey matter covariance showed higher prediction accuracy for early progression of N-t-M. CONCLUSIONS: Our findings are the first to report grey matter covariance changes in MCI development and reversion and highlight the necessity of including grey matter covariance changes along with hippocampal degeneration in the early detection of MCI and Alzheimer's disease.

Tau as a biomarker of cognitive impairment and neuropsychiatric symptom in Alzheimer's disease.

The A/T/N research framework has been proposed for the diagnosis and prognosis of Alzheimer's disease (AD). However, the spatial distribution of ATN biomarkers and their relationship with cognitive impairment and neuropsychiatric symptoms (NPS) need further clarification in patients with AD. We scanned 83 AD patients and 38 cognitively normal controls who independently completed the mini-mental state examination and Neuropsychiatric Inventory scales. Tau, Aß, and hypometabolism spatial patterns were characterized using Statistical Parametric Mapping together with [18F]flortaucipir, [18F]florbetapir, and [18F]FDG positron emission tomography. Piecewise linear regression, two-sample t-tests, and support vector machine algorithms were used to explore the relationship between tau, Aß, and hypometabolism and cognition, NPS, and AD diagnosis. The results showed that regions with tau deposition are region-specific and mainly occurred in inferior temporal lobes in AD, which extensively overlaps with the hypometabolic regions. While the deposition regions of Aß were unique and the regions affected by hypometabolism were widely distributed. Unlike Aß, tau and hypometabolism build up monotonically with increasing cognitive impairment in the late stages of AD. In addition, NPS in AD were associated with tau deposition closely, followed by hypometabolism, but not with Aß. Finally, hypometabolism and tau had higher accuracy in differentiating the AD patients from controls (accuracy = 0.88, accuracy = 0.85) than Aß (accuracy = 0.81), and the combined three were the highest (accuracy = 0.95). These findings suggest tau pathology is superior over Aß and glucose metabolism to identify cognitive impairment and NPS. Its results support tau accumulation can be used as a biomarker of clinical impairment in AD.

Brain mechanisms underlying neuropsychiatric symptoms in Alzheimer's disease: a systematic review of symptom-general and -specific lesion patterns.

Neuropsychiatric symptoms (NPSs) are common in patients with Alzheimer's disease (AD) and are associated with accelerated cognitive impairment and earlier deaths. This review aims to explore the neural pathogenesis of NPSs in AD and its association with the progression of AD. We first provide a literature overview on the onset times of NPSs. Different NPSs occur in different disease stages of AD, but most symptoms appear in the preclinical AD or mild cognitive impairment stage and develop progressively. Next, we describe symptom-general and -specific patterns of brain lesions. Generally, the anterior cingulate cortex is a commonly damaged region across all symptoms, and the prefrontal cortex, especially the orbitofrontal cortex, is also a critical region associated with most NPSs. In contrast, the anterior cingulate-subcortical circuit is specifically related to apathy in AD, the frontal-limbic circuit is related to depression, and the amygdala circuit is related to anxiety. Finally, we elucidate the associations between the NPSs and AD by combining the onset time with the neural basis of NPSs.

Sex Differences in Cortical Morphometry and White Matter Microstructure During Brain Aging and Their Relationships to Cognition.

Changes in brain structure are associated with aging, and accompanied by the gradual deterioration of cognitive functions, which manifests differently in males and females. Here, we quantify the age-related spatial aging patterns of brain gray and white matter structures, their volume reduction rate, their relationships with specific cognitive functions, as well as differences between males and females in a cross-sectional nondementia dataset. We found that both males and females showed extensive age-related decreases in the volumes of most gray matter and white matter regions. Females have larger regions where the volume decreases with age and a greater slope (females: 0.199%, males: 0.183%) of volume decrease in gray matter. For white matter, no significant sex differences were found in age-related regions, and the slope of volume decrease. More significant associations were identified between brain structures and cognition in males during aging than females. This study explored the age-related regional variations in gray matter and white matter, as well as the sex differences in a nondemented elderly population. This study helps to further understand the aging of the brain structure and sex differences in the aging of brain structures and provides new evidence for the aging of nondemented individuals.