Alzheimer's disease (AD) is the most common type of cognitive impairment in the elderly. In this report, we presented a case of a 52-year-old woman with rapid disease progression within 6 months. She was diagnosed with mild dementia according to the clinical symptoms and neuropsychological assessment results. Based on the results of neuropathological proteins in cerebrospinal fluid, cranial magnetic resonance imaging, and positron emission tomography/computed tomography, the patient showed the presence of β amyloid deposition, pathologic tau along with neurodegeneration [A+T+(N+)], indicative of AD. Whole exome sequencing revealed a heterozygous C-to-T missense mutation of nucleotide 3,755 (c.3755C > T) in exon 25 of the angiotensin converting enzyme (ACE) gene on chromosome 17q23 (rs762056936).
Background Malnutrition is the most common nutritional issue in Alzheimer’s disease (AD) patients, but there is still a lack of a comprehensive evaluation of the nutritional status in AD patients. This study aimed to determine the potential association of various nutritional indices with AD at different stages. Methods Subjects, including individuals with normal cognition (NC) and patients diagnosed with AD, were consecutively enrolled in this cross-sectional study. Demographics, body composition, dietary patterns, nutritional assessment scales and nutrition-related laboratory variables were collected. Binary logistics regression analyses and receiver operating characteristic (ROC) curves were used to indicate the association between nutrition-related variables and AD at different stages. Results Totals of 266 subjects, including 73 subjects with NC, 72 subjects with mild cognitive impairment due to AD (AD-MCI) and 121 subjects with dementia due to AD (AD-D) were included. There was no significant difference in dietary patterns, including Mediterranean diet and Mediterranean-DASH diet intervention for neurodegenerative delay (MIND) diet between the three groups. Lower BMI value, smaller hip and calf circumferences, lower Mini Nutritional Assessment (MNA) and Geriatric Nutritional Risk Index (GNRI) scores, and lower levels of total protein, albumin, globulin, and apolipoprotein A1 were associated with AD (all p < 0.05). Total protein and albumin levels had the greatest ability to distinguish AD from non-AD (AUC 0.80, 95% CI 0.74–0.84, p < 0.001), increased by combining calf circumference, MNA score and albumin level (AUC 0.83, 95% CI 0.77–0.88, p < 0.001). Albumin level had the greatest ability to distinguish NC from AD-MCI (AUC 0.75, 95% CI 0.67–0.82, p < 0.001), and MNA score greatest ability to distinguish AD-MCI from AD-D (AUC 0.72, 95% CI 0.65–0.78, p < 0.001). Conclusion Nutritional status of AD patients is significantly compromised compared with normal controls, and tends to be worsened with AD progresses. Early identification and intervention of individuals with nutritional risk or malnutrition may be significantly beneficial for reducing the risk, development, and progression of AD.
This study aimed to explore the clinical characteristics and alteration of orexinergic level in cerebrospinal fluid (CSF) and the volumes of brain grey and white matters, and investigate the roles of orexinergic level on the association between brain atrophy and depression in Alzheimer's disease (AD) patients. The demographic variables of 156 participants were collected. Orexinergic level in CSF and the volumes of brain grey and white matters were evaluated. The correlations of orexinergic level in CSF with depression and brain volume in AD patients were analyzed. The mediating effect of orexinergic level in CSF on the association between brain atrophy and depression in AD patients was investigated. The joint predictive value of orexinergic level in CSF and brain volume for depression in AD patients was established. AD with depression patients showed significantly elevated levels of orexin A and orexin B in CSF; orexin A level in CSF was positively correlated with HAMD score in AD patients. The elevated orexin A level in CSF mediated 49.6% of total association between the decreased grey matter volume of right dorsal medial thalamic nucleus and depression, and 50.3% of total association between the reduced white matter volume of left amygdala and depression. Combinations of above parameters could predict depression in AD patients with a significantly high area under the curve (AUC = 0.841). Therefore, the elevated orexin A level in CSF mediates its effect on the atrophy of the right dorsal medial thalamic nucleus and the white matter of the left amygdala, eventually alleviating depression in AD.
Abstract Aims This study aimed to comprehensively explore the nutrition and gait of AD patients at different stages and the relationship between them. Methods A total of 85 AD patients were consecutively enrolled in this cross‐sectional study and divided into the mild cognitive impairment (MCI) due to AD (AD‐MCI) and the dementia due to AD (AD‐D) groups. Demographic information, nutritional status, and gait performance were compared between the two groups, and the correlation between nutritional status and gait performance was subsequently analyzed by Pearson and Spearman correlation analyses. Results The AD‐D group had lower scores on Mini‐Nutritional Assessment (MNA) and MNA m scales, lower levels of urea nitrogen, folic acid, and vitamin B 12 in blood, and higher homocysteine level than those in the AD‐MCI group (all p < 0.05). The AD‐D group had slower step speed, shorter step length, and shorter stride length than those in the AD‐MCI group (all p < 0.05). AD patients with decreased scores of MNA and MNA m scales, and declined levels of urea nitrogen and vitamin B 12 in blood had reduced gait speed and gait cadence, and prolonged step length time and stride length time, whereas homocysteine showed the almost opposite results (all p < 0.05). In the AD‐MCI group, the score of scale was negatively correlated with the coefficient of variation (CV) of stride length, and the folic acid level was negatively correlated with the CV of stride length and cadence (all p < 0.05). Conclusions AD patients at the dementia stage had worse nutritional status and gait performance than those at the MCI stage, which was associated with worse global cognition and activities of daily living. Poorer nutritional status was associated with higher gait variability in patients at the MCI stage and with poorer gait performance in patients at the dementia stage. Early identification and intervention of patients with nutritional risk or malnutrition may improve gait performance, thus reducing the risk of falling and cognitive decline, as well as the mortality.
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