Associations of depressive symptoms with white matter abnormalities and regional cerebral blood flow in patients with amnestic mild cognitive impairment.

AIM: Depressive symptoms are one of the most common neuropsychiatric symptoms in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD), although the pathophysiologies of the depressive symptoms that occur in these diseases have not been elucidated to date. In this study, we therefore investigated the associations between depressive symptoms and cognitive performance, white matter abnormalities, and regional cerebral blood flow (rCBF) in amnestic MCI patients. METHODS: Thirty-eight patients with amnestic MCI were analyzed. The volumes of periventricular hyperintensities (PVH) and deep white matter hyperintensities (DWMH) were measured on T2-fluid-attenuated inversion recovery magnetic resonance imaging using the imaging software 3D-slicer. Associations between the Geriatric Depression Scale (GDS) score and other neuropsychological test scores on the one hand and the PVH and DWMH volumes on the other were analyzed. Voxel-wise correlations of rCBF with GDS score, after controlling for the effects of age, were investigated using SPM8 software. RESULTS: Significant correlations were identified between GDS score, Trail Making Test B and apathy scale scores on the one hand and PVH volume on the other. A significant negative association between GDS score and rCBF was identified in the right dominant bilateral dorsolateral prefrontal cortex (DLPFC). CONCLUSIONS: Depressive symptoms are significantly associated with PVH volume in MCI patients. The rCBF of the DLPFC was significantly associated with depressive symptoms, suggesting that this area might be closely involved in the pathogenesis of the depressive symptoms observed in MCI patients. Geriatr Gerontol Int 2022; 22: 846-850.

Association of regional white matter hyperintensity volumes with cognitive dysfunction and vascular risk factors in patients with amnestic mild cognitive impairment.

AIM: White matter hyperintensities (WMH) obtained by magnetic resonance imaging (MRI) have been reported to promote neurodegeneration and cognitive decline in patients with mild cognitive impairment (MCI). However, little is known about the association between regional WMH (rWMH) and cognitive dysfunction in MCI. We hence investigated the associations between rWMH volumes and cognitive dysfunction in MCI. METHODS: Thirty-eight subjects with amnestic MCI were analysed. The volumes of periventricular hyperintensities (PVH) and deep WMH (DWMH) were measured on a T2-FLAIR MRI using a 3D-slicer, and regional PVH and DWMH (rPVH and rDWMH) volumes were calculated. The associations of rPVH and rDWMH volumes with cognition and blood levels of various molecules were investigated. Furthermore, rPVH and rDWMH volumes were compared between MCI with vascular risk factors, such as hypertension, diabetes mellitus (DM), and dyslipidemia, and those without these risk factors. RESULTS: rPVH volume (bilateral cornu frontale, pars parietalis, and cornu occipitale) positively correlated with Trail Making Test-A/B scores and CysC level, whereas rDWMH volume did not correlate with any of the items. rPVH volumes (right cornu frontale, bilateral pars parietalis and cornu occipitale, and right pars temporalis) and rDWMH volumes (left frontal and parietal lobes) were significantly larger in MCI patients with DM than in those without. CONCLUSIONS: PVH volumes (bilateral areas of cornu frontale, pars parietalis, and cornu occipitale) were closely associated with attention and executive dysfunction. Serum CysC level and DM were associated with WMH volume, suggesting that CysC level and DM might be important markers for determining treatment strategies for white matter abnormalities in MCI. Geriatr Gerontol Int 2021; 21: 644-650.

Association of White Matter Hyperintensity Progression with Cognitive Decline in Patients with Amnestic Mild Cognitive Impairment.

BACKGROUND: White matter hyperintensities (WMH) on MRI have been reported to increase the risk of conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD). However, effects of the progression of WMH on the cognition of patients with MCI remains unclear to date. OBJECTIVE: To investigate the association between WMH progression and cognitive decline in amnestic MCI patients. METHODS: Thirty-eight subjects with amnestic MCI were analyzed prospectively every year for 2 years. Fourteen MCI subjects dropped out on the final visit, and therefore 24 subjects with MCI were analyzed for the entire duration. The volumes of periventricular hyperintensities (PVH) and deep WMH (DWMH) were measured on T2 FLAIR using the 3D-slicer. The associations between PVH/DWMH progression and cognitive decline were investigated. RESULTS: An increase in DWMH volume significantly correlated with changes in Mini-Mental State Examination and category verbal fluency scores, whereas an increase in PVH volume did not correlate with changes in any item. CONCLUSION: DWMH progression was closely associated with a decline in frontal lobe function and semantic memory, suggesting that WMH progression might affect some AD pathophysiologies in amnestic MCI patients.

Association of serum cystatin C with white matter abnormalities in patients with amnestic mild cognitive impairment.

AIM: White matter hyperintensities (WMH) on MRI have been reported to be a risk factor for the conversion from mild cognitive impairment (MCI) to Alzheimer's disease, although the reason remains unclear. In the present study, we hence investigated the associations between WMH volumes and cognitive function, blood levels of various molecules, and the presence of lifestyle-associated diseases in patients with amnestic MCI. METHODS: The initial data of 38 patients with amnestic MCI and 10 normal control individuals were analyzed. The volumes of periventricular hyperintensities (PVH) and deep WMH (DWMH) were measured on T2 fluid-attenuated inversion recovery using the imaging software, 3D Slicer; and the association between PVH/DWMH volumes and cognitive function, blood levels of molecules (such as cystatin C [CysC], 25-hydroxyvitamin D and homocysteine) and the presence of lifestyle-associated diseases (such as hypertension, hyperlipidemia and diabetes mellitus) were analyzed. RESULTS: In the MCI group, the PVH volume : intracranial volume ratio significantly correlated with Trail Making Test-A/B scores and CysC level by Pearson's analysis, and the PVH volume : intracranial volume ratio significantly correlated with only CysC levels, whereas the DWMH volume : intracranial volume ratio did not correlate with any items at all by linear multiple regression analysis. CONCLUSIONS: PVH volume was closely associated with frontal lobe dysfunction, particularly with attention and executive dysfunction. Serum CysC level was associated with PVH volume, which suggests that CysC might be a useful marker for determining treatment strategies for white matter abnormalities in amnestic MCI. Geriatr Gerontol Int 2019; 19: 1036-1040.

Neuroimaging Characteristics of Frailty Status in Patients with Alzheimer's Disease.

BACKGROUND/OBJECTIVE: Although frailty is closely linked to dementia, particularly Alzheimer's disease (AD), underlying pathophysiology of frailty associated with AD remains uncertain. This study aimed to investigate differences in structural and functional brain imaging abnormalities between AD with and without frailty. METHODS: A total of 191 outpatients with probable AD (men: 91; women: 100; age: 80.7±6.3 years) who underwent both magnetic resonance imaging (MRI) and single-photon emission computed tomography (SPECT) were enrolled in this study. Frailty was determined in accordance with the Obu study Health Promotion for the Elderly. We compared numbers of small infarctions in the subcortical gray and white matter and severity of white matter abnormalities (periventricular hyperintensity [PVH] and deep white matter hyperintensity [DWMH]) on MRI, and regional cerebral blood flow (rCBF) changes on SPECT between AD with and without frailty. RESULTS: The prevalence of frailty was 43.4% in patients with AD. PVH and DWMH scores were significantly higher in AD with frailty compared to those without frailty. AD with frailty had a trend of decreased rCBF in the bilateral anterior cingulate gyrus, whereas those without frailty tend to have decreased rCBF in the left dominant parietal lobe and precuneus. CONCLUSION: Our MRI and SPECT imaging studies suggest different underlying pathophysiology in the brain between AD with frailty and without frailty.

Caregivers' education decreases depression symptoms and burden in caregivers of patients with dementia.

OBJECTIVE: To determine whether providing education to caregivers of patients with dementia decreases their depression symptoms and burden. METHODS: Eighty-three outpatients with dementia being treated at the Memory Clinic of Tokyo Medical University Hospital and their caregivers were enrolled. Forty-seven caregivers were enrolled in the caregivers' education (EDU) group and 36 were enrolled in the control (CTL) group. Caregivers were assessed for depression, burden, and quality of life (QoL). Patients were assessed for cognition, psychological symptoms, and QoL. Assessments were carried out at baseline and at 3 months (3M). Caregivers in the EDU group received lectures on symptoms and progression of dementia, management of symptoms, use of social resources etc. RESULTS: At 3M, prevalence of depression symptoms in the EDU group significantly decreased from 36% to 17%, whereas it significantly increased from 22% to 50% in the CTL group. Depression and burden were significantly improved at 3M in the EDU group, whereas they significantly worsened in the CTL group. Psychological symptoms showed a lower tendency at 3M for the EDU group. No significant changes in QoL of caregivers and patients were found in either group. CONCLUSIONS: Providing education to caregivers of patients with dementia improves their depression symptoms and sense of burden, and tends to improve the behaviour and psychological symptoms of dementia in the patients. Providing education to caregivers of dementia patients may hence result in beneficial effects for both the patients and their caregivers, and should be widely used in dementia care.

Amyloid and Tau Positron Emission Tomography in Suggested Diabetesrelated Dementia.

BACKGROUND: Type 2 diabetes mellitus (DM) has been shown to increase the risk for cognitive decline and dementia, such as Alzheimer disease (AD) and vascular dementia (VaD). In addition to AD and VaD, there may be a dementia subgroup associated with specific DM-related metabolic abnormalities rather than AD pathology or cerebrovascular disease, referred to as diabetes-related dementia (DrD). METHOD: We studied 11C-PiB and 11C-PBB3 positron emission tomography (PET) in 31 subjects with DrD and 5 subjects with AD associated with DM to assess amyloid and tau deposits in the brain. RESULTS: All subjects with AD showed both positive PiB and PBB3. However, only 12 out of 31 subjects (39%) with DrD showed positive PiB, whereas 17 out of 21 subjects (81%) who underwent PBB3 PET showed positive PBB3. Depending on the positivity of PiB and PBB3, we classified 21 subjects into a negative PiB and a positive PBB3 pattern (11 cases, 52%), indicating tauopathy, a positive PiB and a positive PBB3 pattern (6 cases, 29%), indicating AD pathology, or a negative PiB and a negative PBB3 pattern (4 cases, 19%). Among 11 subjects showing a negative PiB and a positive PBB3 pattern, there were 2 PBB3 deposit patterns, including the medial temporal lobe only and extensive neocortex beyond the medial temporal lobe. CONCLUSION: DrD showed variable amyloid and tau accumulation patterns in the brain. DrD may be associated predominantly with tau pathology, in addition to AD pathology and non-amyloid/non-tau neuronal damage due to DM-related metabolic abnormalities.

Cerebrospinal fluid analysis in individuals with diabetes-related dementia.

•CSF P-tau and Aß42 show normal levels in diabetes-related dementia.•Diabetes-related dementia may have a different underlying pathology from AD.•CSF analysis is useful for the differentiation of diabetes-related dementia from AD.

Neuroimaging for diagnosing dementia with Lewy bodies: What is the best neuroimaging technique in discriminating dementia with Lewy bodies from Alzheimer's disease?

AIM: We compared the diagnostic value of four neuroimaging techniques, namely, 123 I-2ß-Carbomethoxy-3ß-(4-iodophenyl)-N-(3-fluoropropyl) nortropane (123 I-FP-CIT) dopamine transporter single-photon emission computed tomography (DAT-SPECT), magnetic resonance imaging, perfusion SPECT and 123 I-metaiodobenzyl-guanidine myocardial scintigraphy in differentiating dementia with Lewy bodies (DLB) from Alzheimer's disease (AD). METHODS: A total of 32 patients with probable AD and 32 patients with probable DLB were enrolled in the present study. For the comparison study, we used the specific binding ratio for DAT-SPECT, the heart-to-mediastinum ratio in the delay phase for 123 I-metaiodobenzyl-guanidine myocardial scintigraphy, z-scores in the medial occipital lobe for perfusion SPECT and z-scores of hippocampal atrophy using a voxel-based specific regional analysis system for AD for magnetic resonance imaging. RESULTS: DAT-SPECT enabled more accurate differentiation of DLB from AD than other methods. 123 I-metaiodobenzyl-guanidine myocardial scintigraphy enabled more accurate differentiation of DLB from AD than magnetic resonance imaging and perfusion SPECT. CONCLUSIONS: In agreement with the recent consensus clinical diagnostic criteria for DLB, we confirmed that the diagnostic accuracy of DAT-SPECT imaging is significantly higher than other neuroimaging techniques. Geriatr Gerontol Int 2017; 17: 819-824.

Decreased Muscle Strength and Quality in Diabetes-Related Dementia.

BACKGROUND/AIMS: Diabetes-related dementia (DrD), a dementia subgroup associated with specific diabetes mellitus (DM)-related metabolic abnormalities, is clinically and pathophysiologically different from Alzheimer disease (AD) and vascular dementia. We determined whether skeletal muscle strength, quality, and mass decrease in individuals with DrD. METHODS: We evaluated grip and knee extension strength, muscle mass, and gait speed in 106 patients with probable AD and without type 2 DM (AD[-DM] group), 74 patients with probable AD and with DM (AD[+DM] group), and 36 patients with DrD (DrD group). Muscle quality was defined as the ratio of muscle strength to muscle mass. RESULTS: Both female and male subjects with DrD showed significantly decreased muscle strength and quality in the upper extremities compared with the subjects with AD[-DM] or AD[+DM]. Female subjects with DrD showed significantly decreased muscle quality in the lower extremities compared with the subjects with AD[-DM]. Both female and male subjects with DrD had a significantly lower gait speed compared with the subjects with AD[-DM]. However, there were no significant differences in muscle mass and the prevalence of sarcopenia between the groups. CONCLUSION: Subjects with DrD showed decreased muscle strength and quality, but not muscle mass, and had a low gait speed.

Peripheral oxidative stress markers in diabetes-related dementia.

AIMS: We previously found that there was a dementia subgroup with characteristics predominantly associated with diabetes mellitus (DM)-related metabolic abnormalities, referred to as "diabetes-related dementia (DrD)." We determined the possible role of oxidative stress in the pathophysiology of DrD. METHODS: In a 2013 study, we classified 175 patients with clinically diagnosed Alzheimer's disease (AD) and DM into four subgroups based on brain imaging. Among them, we measured endogenous plasma anti-oxidants, such as albumin, unconjugated bilirubin and uric acid, and urinary 8-hydroxy-2'-deoxyguanosine and 8-isoprostane in 58 patients of an AD group showing decreased regional cerebral blood flow of the parietotemporal lobe on single-photon emission computed tomography (AD+DM group), and in 35 patients of a DrD group showing neither decreased regional cerebral blood flow of the parietotemporal lobe nor cerebrovascular disease on magnetic resonance imaging, which is strongly associated with DM-related factors. A total of 31 patients with AD and without DM (AD-DM group) were enrolled as a control group. RESULTS: The DrD group showed a significant decrease in plasma levels of anti-oxidants, and a significant increase in urinary 8-hydroxy-2'-deoxyguanosine and 8-isoprostane levels in contrast to the AD-DM and AD+DM groups. Cognitive performance was negatively correlated with urinary 8-hydroxy-2'-deoxyguanosine and 8-isoprostane levels in the DrD group. CONCLUSIONS: These results strongly suggest that a decrease in anti-oxidant levels and an increase in oxidative damage might be involved in the pathophysiology and cognitive decline associated with DrD. Geriatr Gerontol Int 2016; 16: 1312-1318.