Zhongwei Guo

Abnormal baseline brain activity in Alzheimer’s disease patients with depression: a resting-state functional magnetic resonance imaging study

PurposeAs one of the most common mental disorders and the most important precursor of suicide in Alzheimer’s disease (AD), depression is associated with a decline in both well-being and daily functioning. At present, the diagnosis of AD patients with depression (D-AD) is largely dependent on clinical signs and symptoms, and the precise neural correlate underlying D-AD is still not fully understood.MethodsThe current study sought to investigate low-frequency oscillations at the voxel level in D-AD patients based on the amplitude of low-frequency fluctuations (ALFF) measured using resting-state functional magnetic resonance imaging. We examined 22 D-AD patients and 21 non-depressed AD (nD-AD) patients.ResultsThe results revealed that D-AD patients exhibited increased ALFF values in the left caudate and thalamus and decreased ALFF values in the left middle temporal pole compared with nD-AD patients.ConclusionThese findings may provide further insight into the underlying neuropathophysiology of AD with depression.

Decreased functional connectivity between the dorsal anterior cingulate cortex and lingual gyrus in Alzheimer's disease patients with depression

Background Depression is one of the most common psychiatric symptoms in Alzheimers disease (AD), occurring in up to 40% of AD patients. It influences the cognitive function of patients and increases the burden on their caregivers. Currently, there are few effective medical treatments for reducing the symptoms of depression in AD patients. Understanding the underlying neurobiological mechanisms in AD patients with depression (D‐AD) is crucial for developing effective interventions. The anterior cingulate cortex (ACC) is an important brain region involved in emotional and cognitive processing. Several functional magnetic resonance imaging studies have shown that patients with major depressive disorder have structural, functional, and metabolic abnormalities in the ACC. Methods We investigated the resting‐state functional connectivity (FC) of ACC subregions in 15 D‐AD patients and 17 non‐depressed AD (nD‐AD) patients, by parcellating the ACC into the rostral and dorsal ACC (dACC). Results Our results revealed that D‐AD patients have decreased FC between the dACC and the right occipital lobe and right lingual gyrus, compared with nD‐AD patients. Conclusions Decreased FC between the dACC and the right occipital lobe and right lingual gyrus may play an important role in the neuropathophysiology of depression in AD. HighlightsResting State Functional Connectivity was used to examine network communication of the Anterior Cingulate Cortex subregions in non‐depressed Alzheimer’s disease and Alzheimer’s disease with depression.Alzheimer’s disease with depression had lower Functional Connectivity values in the right occipital lobe and lingual gyrus.The decreased FC between dACC and right lingual gyrus may play an important role in the neuropathophysiology of depression in AD.

Fractional amplitude of low-frequency fluctuations is disrupted in Alzheimer’s disease with depression

OBJECTIVE To explore brain activity in AD with depression (D-AD) based on fractional amplitude of low-frequency fluctuation (fALFF). METHODS Twenty-two D-AD and 21 AD without depression patients (nD-AD) were examined by magnetic resonance imaging during resting state. Neuropsychiatric Inventory and Hamilton Depression Rating Scale were employed to assess the severity of depression. We analysed the characteristics of fALFF in D-AD differing from nD-AD. We also examined the correlation between fALFF and the depression severity. RESULTS D-AD patients had higher fALFF in right fusiform gyrus, left caudate nucleus, and right middle temporal gyrus (MTG), meanwhile lower fALFF in supplementary motor area (SMA) than nD-AD patients. CONCLUSIONS Abnormal fALFF changes in fusiform gyrus, caudate nucleus, MTG and SMA may be important neuropathophysiologic characteristics of depression in AD. SIGNIFICANCE We have clarified the potential neuropathological changes of depression in AD based on fALFF method, which is crucial for effective intervention.

1H-MRS asymmetry changes in the anterior and posterior cingulate gyrus in patients with mild cognitive impairment and mild Alzheimer's disease

Alzheimers disease (AD) is the most common cause of dementia worldwide. Amnestic mild cognitive impairment (aMCI) is often the prodromal stage to AD. Most patients with aMCI harbor the pathologic changes of AD and demonstrate transition to AD at a rate of 10%-15% per year. Patients with AD and aMCI experience progressive brain metabolite changes. Accumulating evidence indicates that the asymmetry changes of left and right brain happen in the early stage of AD. However, the features of asymmetry changes in both anterior cingulate gyrus (ACG) and posterior cingulate gyrus (PCG) are still unclear. Here, we examine the left-right asymmetry changes of metabolites in ACG and PCG. Fifteen cases of mild AD patients meeting criteria for probable AD of NINDS-ADRDA, thirteen cases of aMCI according to the Mayo Clinic Alzheimers Disease Research Center criteria, and sixteen cases of age-matched normal controls (NC) received Proton magnetic resonance spectroscopy ((1)H-MRS) for measurement of NAA/mI, NAA/Cr, Cho/Cr, and mI/Cr ratios in the PCG and ACG bilaterally. We analyzed (1)H-MRS data by paired t-test to validate the left-right asymmetry of (1)H-MRS data in the PCG and ACG. In AD, there was a significant difference in mI/Cr between the left and right ACG (P<0.001) and the left and right PCG (P=0.007). In aMCI, there was a significant difference in mI/Cr between the left and right ACG (P<0.001). In NC, there were no differences in the ratio value of metabolites NAA/mI, NAA/Cr, Cho/Cr, and mI/Cr between the left and right ACG and PCG. Thus, the left-right asymmetry of mI/Cr in the ACG and PCG may be an important biological indicator of mild AD.

The Abnormal Functional Connectivity between the Hypothalamus and the Temporal Gyrus Underlying Depression in Alzheimer’s Disease Patients

Hypothalamic communication with the rest of the brain is critical for accomplishing a wide variety of physiological and psychological functions, including the maintenance of neuroendocrine circadian rhythms and the management of affective processes. Evidence has shown that major depressive disorder (MDD) patients exhibit increased functioning of the hypothalamic-pituitary-adrenal (HPA) axis. Neurofibrillary tangles are also found in the hypothalamus of Alzheimer’s disease (AD) patients, and AD patients exhibit abnormal changes in the HPA. However, little is known of how the hypothalamus interacts with other brain regions in AD patients with depression (D-AD). Functional connectivity (FC) analysis explores the connectivity between brain regions that share functional properties. Here, we used resting-state (rs) magnetic resonance imaging (MRI) technology and the FC method to measure hypothalamic connectivity across the whole brain in 22 D-AD patients and 21 non-depressed AD patients (nD-AD). Our results showed that D-AD patients had reduced FC among the hypothalamus, the right middle temporal gyrus (MTG) and the right superior temporal gyrus (STG) compared with the FC of nD-AD patients, suggesting that the abnormal FC between the hypothalamus and the temporal lobe may play a key role in the pathophysiology of depression in AD patients.

Abnormal functional connectivity of the posterior cingulate cortex is associated with depressive symptoms in patients with Alzheimer’s disease

Background Depressive symptoms are significant and very common psychiatric complications in patients with Alzheimer’s disease (AD), which can aggravate the decline in social function. However, changes in the functional connectivity (FC) of the brain in AD patients with depressive symptoms (D-AD) remain unclear. Objective To investigate whether any differences exist in the FC of the posterior cingulate cortex (PCC) between D-AD patients and non-depressed AD patients (nD-AD). Materials and methods We recruited 15 D-AD patients and 17 age-, sex-, educational level-, and Mini-Mental State Examination (MMSE)-matched nD-AD patients to undergo tests using the Neuropsychiatric Inventory, Hamilton Depression Rating Scale, and 3.0T resting-state functional magnetic resonance imaging. Bilateral PCC were selected as the regions of interest and between-group differences in the PCC FC network were assessed using Student’s t-test. Results Compared with the nD-AD group, D-AD patients showed increased PCC FC in the right amygdala, right parahippocampus, right superior temporal pole, right middle temporal lobe, right middle temporal pole, and right hippocampus (AlphaSim correction; P<0.05). In the nD-AD group, MMSE scores were positively correlated with PCC FC in the right superior temporal pole and right hippocampus (false discovery rate corrected; P<0.05). Conclusion Differences were detected in PCC FC between nD-AD and D-AD patients, which may be related to depressive symptoms. Our study provides a significant enhancement to our understanding of the functional mechanisms underlying D-AD.

Abnormal changes in functional connectivity between the amygdala and frontal regions are associated with depression in Alzheimer’s disease

PurposeThe aim of the present study was to investigate the functional connectivity (FC) of Alzheimer’s disease patients with depression (D-AD) based on an amygdalar seed using resting-state functional magnetic resonance imaging (rs-fMRI).MethodsTwenty-one non-depressed AD (nD-AD) patients and 21 D-AD patients underwent rs-fMRI. The Hamilton Depression Rating Scale and Neuropsychiatric Inventory were used to evaluate the severity of depression. The amygdala was used as the seed for FC analysis. The FC differences between the two groups were evaluated by two-sample t tests, and the correlation of FC changes with depressive severity was analyzed by Pearson correlational analysis.ResultsCompared with the nD-AD patients, D-AD patients had increased FC values between the amygdala and orbitofrontal cortex and decreased FC values among the amygdala, medial prefrontal cortex, and inferior frontal gyrus.ConclusionThese data suggest that abnormal amygdala-prefrontal FC may be an important characteristic of AD patients with depression.

Altered Intrinsic Coupling between Functional Connectivity Density and Amplitude of Low-Frequency Fluctuation in Mild Cognitive Impairment with Depressive Symptoms

Neuroimaging studies have demonstrated that major depressive disorder increases the risk of dementia in older individuals with mild cognitive impairment. We used resting-state functional magnetic resonance imaging to explore the intrinsic coupling patterns between the amplitude and synchronisation of low-frequency brain fluctuations using the amplitude of low-frequency fluctuations (ALFF) and the functional connectivity density (FCD) in 16 patients who had mild cognitive impairment with depressive symptoms (D-MCI) (mean age: 69.6 ± 6.2 years) and 18 patients with nondepressed mild cognitive impairment (nD-MCI) (mean age: 72.1 ± 9.7 years). Coupling was quantified as the correlations between the ALFF values and their associated FCDs. The results showed that the ALFF values in the D-MCI group were higher in the left medial prefrontal cortex (mPFC) and lower in the right precentral gyrus (preCG), and the FCD values were higher in the left medial temporal gyrus (MTG) than those in the nD-MCI group. Further, correlation analyses demonstrated that, in the D-MCI group, the mPFC was negatively correlated with the MTG. These findings may relate to the characteristics of mood disorders in patients with MCI, and they offer further insight into the neuropathophysiology of MCI with depressive symptoms.