Clinical Significance of Physical Frailty in Subjects With Subjective Cognitive Decline: A Prospective Study With Amyloid PET Data.

BACKGROUND AND PURPOSE: Physical frailty is known to be closely associated with cognitive impairment and to be an early sign of Alzheimer's disease. We aimed to understand the characteristics of physical frailty and define factors associated with physical frailty in subjects with subjective cognitive decline (SCD) by analyzing amyloid data. METHODS: We prospectively enrolled subjects with SCD from a cohort study to identify predictors for the clinical progression to mild cognitive impairment or dementia from SCD (CoSCo). All of the subjects underwent brain magnetic resonance imaging, and brain amyloid positron-emission tomography (PET) to detect amyloid beta plaques. Self-reported exhaustion, handgrip strength, and gait speed were used to measure physical frailty. RESULTS: Of 120 subjects with SCD, 26 (21.7%) were amyloid-positive in PET. Female (odds ratio [OR]=3.79, p=0.002) and amyloid-PET-positive (OR=3.80, p=0.008) subjects with SCD were at high risks of self-reported exhaustion. Amyloid PET positivity (OR=3.22, p=0.047) and high burden from periventricular white-matter hyperintensity (OR=3.34, 95% confidence interval=1.18-9.46, p=0.023) were significantly associated with a weaker handgrip. The subjects with SCD with self-reported exhaustion and weaker handgrip presented with lower cognitive performance in neuropsychological tests, especially for information processing speed and executive function. Subjects with a slower gait performed worse in visual memory function tests. CONCLUSIONS: Amyloid PET positivity was associated with a higher risk of self-reported exhaustion and weaker handgrip in subjects with SCD. The subjects with SCD and physical frailty also performed worse in neuropsychological tests.

A comparison of sociobehavioral impact on cognitive preservation in Alzheimer's disease between Taiwan and Korea: A cross-national study.

Both Taiwan and Korea are developed countries with different cultures. When encountering the issue of dementia, such sociobehavioral factors have various and different impacts on dementia. We aim to assess the cross-national difference of sociobehavioral impact on cognitive preservation in Alzheimer's disease (AD) between Taiwan and Korea.A uniformed data set was administered regarding AD. We evaluated annual cognitive function using the Mini-Mental State Examination (MMSE), Clinical Dementia Rating sum of box (CDR-SB), and CDR for 2 continuous years. Annual change of scores compared with the baseline indicated cognitive change as preservation or decline. We recorded the sociodemographic variables of interest, including education duration, level of independence, living situation, and marital status. Step-wise regression analyses were performed to determine the independent factors for cognitive preservation.In total, 503 participants in Taiwan and 77 participants in Korea were recruited from 2011 to 2014. The baseline demographic characteristics were different in levels of education, living situation, level of independence, and dementia severity between the 2 countries. With follow-up for 2 years, cognitive preservation was associated with CDR staging at baseline and independence [adjusted odds ratio (OR) = 1.657, 95% confidence interval (95% CI) = 1.109-2.477, P = .014] in the Taiwanese population, whereas cognitive preservation was related to living alone (adjusted OR = 3.316, 95% CI = 1.135-9.687, P = .028) in the Korean population. The levels of education showed inconsistency in cognitive preservation in both countries.Cognitive preservation was associated with independence in the Taiwanese population, whereas cognitive preservation was related to living alone in the Korean population. By practicing relevant socioeconomic support, this might contribute to lessening the negative impact of dementia and preserving cognition in different countries.

The Effect of Daily Low Dose Tadalafil on Cerebral Perfusion and Cognition in Patients with Erectile Dysfunction and Mild Cognitive Impairment.

OBJECTIVE: The aims of this study were to investigate the effects of daily low-dose tadalafil on cognitive function and to examine whether there was a change in cerebral blood flow (CBF) in patients with erectile dysfunction (ED) and mild cognitive impairment. METHODS: Male patients aged 50 to 75 years with at least three months of ED (International Index of Erectile Function [IIEF]-5 score ≤ 21) and mild cognitive impairment (Montreal Cognitive Assessment [MoCA] score ≤ 22) were included in the study. The subjects were prescribed a low-dose PDE5 inhibitor (tadalafil 5 mg) to be taken once daily for eight weeks. Changes in MoCA score and single-photon emission computed tomography (SPECT) study between the two time-points were assessed by paired t tests. RESULTS: Overall, 30 male patients were assigned to the treatment group in this study and 25 patients completed the eight-week treatment course. Five patients were withdrawn due to adverse events such as myalgia and dizziness. Mean baseline IIEF and MoCA scores were 7.52 ± 4.84 and 18.92 ± 1.78. After the eight-week treatment, mean IIEF and MoCA scores were increased to 12.92 ± 7.27 (p < 0.05) and 21.8 ± 1.71 (p < 0.05), respectively. Patients showed increased relative regional CBF in the postcentral gyrus, precuneus, and brainstem after tadalafil administration versus at baseline (p < 0.001). CONCLUSION: The results of this prospective clinical study suggest that daily use of tadalafil 5 mg increases some regional CBF and improves cognitive function in patients with ED and mild cognitive impairment.

Different Cortical Thinning Patterns Depending on Their Prognosis in Individuals with Subjective Cognitive Decline.

BACKGROUND AND PURPOSE: Subjective cognitive decline (SCD) may be the first stage corresponding to subtle cognitive changes in patients with Alzheimer's disease (AD) spectrum disorders. We evaluated the differences in cortical thinning patterns among patients with SCD who progressed to mild cognitive impairment or dementia (pSCD), those who remained stable (sSCD), and healthy normal controls (NCs). METHODS: We retrospectively recruited SCD subjects (14 pSCD and 21 sSCD cases) and 29 NCs. Structural 3-dimensional-T1-weighted magnetic resonance imaging was performed using a single 1.5 Tesla scanner. Freesurfer software was used to map cortical thickness for group comparisons. RESULTS: Compared with NC group, the sSCD group showed diffuse cortical atrophy associated with bilateral fronto-parieto-temporal area. The pSCD group showed further characteristic cortical atrophy in AD-vulnerable regions including the inferior parieto-temporal and middle temporal areas. Cortical thinning in the bilateral medial frontal areas was observed in patients with sSCD and involved the right inferior temporal and left precentral areas in those with pSCD. CONCLUSIONS: Our study showed that SCD subjects exhibit different cortical thinning patterns depending on their prognosis.

Hippocampal and entorhinal structures in subjective memory impairment: a combined MRI volumetric and DTI study.

BACKGROUND: Subjective memory impairment (SMI) is common among older adults. Increasing evidence suggests that SMI is a risk factor for future cognitive decline, as well as for mild cognitive impairment and dementia. Medial temporal lobe structures, including the hippocampus and entorhinal cortex, are affected in the early stages of Alzheimer's disease. The current study examined the gray matter (GM) volume and microstructural changes of hippocampal and entorhinal regions in individuals with SMI, compared with elderly control participants without memory complaints. METHODS: A total of 45 participants (mean age: 70.31 ± 6.07 years) took part in the study, including 18 participants with SMI and 27 elderly controls without memory complaints. We compared the GM volume and diffusion tensor imaging (DTI) measures in the hippocampal and entorhinal regions between SMI and control groups. RESULTS: Individuals with SMI had lower entorhinal cortical volumes than control participants, but no differences in hippocampal volume were found between groups. In addition, SMI patients exhibited DTI changes (lower fractional anisotropy (FA) and higher mean diffusivity in SMI) in the hippocampal body and entorhinal white matter compared with controls. Combining entorhinal cortical volume and FA in the hippocampal body improved the accuracy of classification between SMI and control groups. CONCLUSIONS: These findings suggest that the entorhinal region exhibits macrostructural as well as microstructural changes in individuals with SMI, whereas the hippocampus exhibits only microstructural alterations.

Impact of Alzheimer's Disease in Nine Asian Countries.

BACKGROUND: Asia will soon have the majority of demented patients in the world. OBJECTIVE: To assess dementia using a uniform data system to update the current status of dementia in Asia. METHODS: A uniformed data set was administered in Taiwan, China, Hong Kong, Korea, Japan, Philippines, Thailand, Singapore, and Indonesia to gather data with regard to Alzheimer's disease (AD) and its related issues for these countries. RESULTS: In total, 2,370 AD patients and their caregivers were recruited from 2011 to 2014. The demographic characteristics of these patients and the relationships between patients and caregivers were different among individuals in these countries (p < 0.001). Of note, the family history for having dementia was 8.2% for females in contrast to 3.2% for males. CONCLUSION: Our study highlighted the differences in dementia assessment and care in developing versus developed countries. Greater effort with regard to studying dementia, especially in developing countries, is necessary.

Prevalence and treatment pattern of Parkinson's disease dementia in Korea.

AIM: The aim of the present study was to investigate the point prevalence of dementia and mild cognitive impairment (MCI) in patients with Parkinson's disease (PD). METHODS: A total of 1200 patients with PD from 12 hospitals were included in the study. All patients were grouped into normal cognition, MCI and dementia subgroups. General cognitive status and dementia severity were assessed by the Korean version of the Mini-Mental State Examination, Clinical Dementia Rating and Global Deterioration Scale, and parkinsonian motor status was assessed by the Hoehn and Yahr staging score. Associated sleep behaviors and other medical conditions were checked. Prescribing patterns of antidementia medications were analyzed. RESULTS: Cognitive impairment was frequent in patients with PD; MCI was found in 38.9% of patients, whereas dementia was in 38.3% of patients. The prevalence of cognitive impairment increased with increasing age and longer disease duration, and the symptoms of postural instability and symptoms mimicking rapid eye movement sleep behavior disorder were associated with cognitive impairment. Many dementia patients (95.2%) and 23.6% of MCI patients were treated with antidementia drugs, with rivastigmine the most frequently used. CONCLUSION: The point prevalence of cognitive impairment in patients with PD was 77.2%. Cognitive impairment was associated with age, disease duration and specific parkinsonian motor/non-motor symptoms. Over 90% of the patients with dementia were treated with antidementia medication, and rivastigmine was the most frequently used for the management of dementia.

Arterial stiffness and impaired renal function in patients with Alzheimer's disease.

Impaired renal function is regarded as a risk factor for vascular disease, and is associated with an increasing pulse wave velocity. Both renal dysfunction and arterial stiffness are associated with cognitive impairment and dementia. However, there have been few studies that have evaluated the relationship between albuminuria and arterial stiffness and Alzheimer's disease (AD). We investigated renal dysfunction and arterial stiffness in AD, as compared to normal controls, patients with subjective memory impairment (SMI), and patients with mild cognitive impairment (MCI). Case-control comparisons were made between 29 patients with AD, 27 with MCI, 14 with SMI, and 25 healthy controls. All patients underwent clinical and neuropsychological assessments. The urine albumin/creatinine ratio and estimated glomerular filtration rate (eGFR) were determined. Pulse wave velocity and the ankle-brachial index were used to evaluate arterial stiffness. The urine albumin/creatinine ratio and eGFR were significantly different in patients with AD, compared with the results from cognitive normal controls. The pulse wave velocity was increased and the ankle-brachial index was decreased in AD. The eGFR was well correlated with other indices and decreasing eGFR was independently associated with cognitive decline. In conclusion, albuminuria, a decreased glomerular filtration rate, an increased pulse wave velocity, and a decreased ankle-brachial index were associated with AD. These finding suggests that impaired renal functions and arterial stiffness are related to AD, in which a vascular mechanism plays a prominent role in the cognitive dysfunction associated with the disease.

Pathological correlates of white matter hyperintensities on magnetic resonance imaging.

BACKGROUND/AIMS: We investigated the histopathological correlates of white matter hyperintensities (WMHs) in participants with Alzheimer's disease (AD) or cerebrovascular disease, and in aged controls. METHODS: We reviewed 57 participants who had neuropathology and in whom neuroimaging was done. In addition to AD pathology, cortical microinfarcts, lacunes, and cerebral hemorrhages were assessed. Small-vessel disease included arteriolosclerosis and cerebral amyloid angiopathy. Postmortem brain tissue corresponding to regions of WMHs was investigated in 14 participants. The variables included: demyelination of the deep and periventricular white matter (WM), atrophy of the ventricular ependyma, and thickness of blood vessels. Partial Spearman's rank test and linear regression analysis, adjusted for age at the clinical evaluation and the duration to death, were performed. RESULTS: The severity of arteriosclerosis was correlated with the volume of periventricular hyperintensity (PVH) estimated by magnetic resonance imaging. Deep white matter hyperintensity (DWMH) volume was correlated with the presence of cortical microinfarcts and cerebral hemorrhages. The severity of the breakdown of the ventricular lining was correlated with PVHs, and DWMHs correlated with the severity of deep WM demyelination. The diameter of small blood vessels was not associated with WMHs. CONCLUSION: WMHs are consistent with small-vessel disease and increase the tissue water content. We found no association between WMHs and the thickness of small blood vessels.

Donepezil treatment in Alzheimer's disease patients with and without cerebrovascular lesions: a preliminary report.

AIM: Donepezil has not been evaluated in Korean patients with Alzheimer's disease (AD) for up to 1 year. The objectives of this study were to evaluate the differential efficacy of donepezil in Korean AD patients with and without concomitant cerebrovascular lesions (CVL). METHODS: This study was a 48-week open-label trial of donepezil in patients with probable AD of mild to moderate severity. CVL were evaluated through magnetic resonance imaging (MRI) findings within 3 months. Efficacy analyses were performed for cognitive, behavioral and functional outcome measures. RESULTS: Concomitant CVL were documented in 35 (30.7%) of the patients on MRI. Seventy-nine (69.3%) of the patients were considered not to have concomitant CVL. The mean Mini-Mental State Examination scores of both patients with and without CVL showed improvement at each evaluation. However, there was no statistical difference in improvement between the groups. CONCLUSION: The presence of CVL should not deter clinicians from treating AD with donepezil.

Impact of tremor severity on cognition in elderly patients with essential tremor.

Several clinical studies have demonstrated that patients with essential tremor (ET) may have cognitive deficits; however, detailed neuropsychological assessments in comparison with motor tasks in patients with ET have not been reported. We conducted a prospective study to determine the correlation of cognition with age, disease duration, and motor task severity in patients with ET. Forty-seven patients with ET who underwent clinical assessment using the Fahn-Tolosa-Marin clinical rating scale and detailed neuropsychological investigation were included. Cognitive decline was significantly correlated with age at the time of examination, educational status, and tremor severity; cognitive decline however, was not related to disease duration or the presence of vascular risk factors. Multiple linear regression analysis revealed that the tremor severity was independently associated with cognitive impairment in patients with ET, regardless of age, gender, educational status, duration of ET symptoms, and vascular risk factors. Our results support the finding that the age at examination and educational status are risk factors associated with dementia in patients with ET, as with other types of dementia. In addition, the relationship between tremor severity and cognitive decline suggests there may be a pathophysiologic association between the two conditions, although the pathologic basis for dementia in the older onset ET cases requires further study.

Cognitive Impairment in Essential Tremor without Dementia.

BACKGROUND AND PURPOSE: Several clinical studies have demonstrated that patients with essential tremor (ET) may have cognitive deficits; however, there are no published data regarding detailed neuropsychological assessments of ET without dementia. We therefore conducted a case-control study of cognitive function in patients with ET. METHODS: The cohort for this study comprised 34 consecutive patients with ET without dementia and 33 age-matched controls, all of who completed a dementia-screening questionnaire and underwent a detailed neuropsychological investigation. RESULTS: Severe impairments were observed in most domains for the ET group compared to the controls, including attention, part of language function, verbal memory, and frontal executive functions. CONCLUSIONS: Our results support the finding that the subclinical cognitive deficits characterized by attention, verbal memory impairments, and executive dysfunction are a clinical feature of ET. In addition, our results also support the finding that age at examination and educational status are the most important risk factors associated with cognitive deficits in patients with ET.

Voxel-based analysis of Tc-99m ECD brain perfusion SPECT in patients with normal pressure hydrocephalus.

Idiopathic normal pressure hydrocephalus (iNPH) is a reversible dementia characterized by gait disturbance, incontinence and dementia. This study investigates the neuropsychological characteristics and changes of regional cerebral blood flow (rCBF) in patients with iNPH. Ten patients who met the criteria of probable iNPH and 13 normal control subjects were evaluated. The general cognitive function and detailed neuropsychological functions were measured by K-MMSE and comprehensive neuropsychological battery. Tc-99m-ethyl cysteinate dimmer (Tc-99m-ECD) single photon emission computed tomography (SPECT) was performed to measure the rCBF and statistical parametric mapping (SPM) and statistical probabilistic brain anatomic map (SPAM) was applied to the objective analysis of SPECT data. On the neuropsychological examination, all the patients showed abnormality in memory, psychomotor speed and frontal executive function. SPM analysis of SPECT images revealed that rCBF in bilateral thalami, right prefrontal area, bilateral anterior and posterior cingulate gyri, right caudate nucleus, and left parahippocampal gyrus was significantly decreased in patients with iNPH compared to normal controls (uncorrected P<0.005). In SPAM analysis, rCBF reduction was observed in bilateral prefrontal area, anterior, posterior cingulate gyri and caudate nuclei. We have found that rCBF changes occurred predominantly in prefrontal and subcortical areas, the changes were associated with frontal subcortical circuit, and the affected frontal subcortical circuit may contribute to the cognitive decline seen in the iNPH patients. The reduction of rCBF and clinical cognitive impairment are closely connected in patients with iNPH.

Cardiac sympathetic denervation and its association with cognitive deficits in Parkinson's disease.

BACKGROUND: There is growing evidence to suggest that cognitive decline in patients with Parkinson's disease (PD) is associated with autonomic involvement, although the clinical and pathological correlations have not been firmly established. OBJECTIVE: We prospectively investigated the pattern of myocardial sympathetic denervation deficits in PD and its correlation with cognitive decline. METHODS: Twenty-eight patients with PD who underwent myocardial (123)I-metaiodobenzylguanidine (MIBG) scintigraphy, clinical assessment of stage and severity of PD and detailed neuropsychological investigation were included in the study. RESULTS: There were significant differences in the MIBG uptake between the PD patients with cognitive deficits and those who did not have cognitive deficits. CONCLUSION: These findings confirm that cognitive decline in patients with PD is associated with autonomic involvement and raises the possibility that the topographical spread of synuclein pathology involving the neocortical areas might be linked to the autonomic system in PD.

Central pontine and extrapontine myelinolysis after alcohol withdrawal.

Central pontine myelinolysis (CPM) and extrapontine myelinolysis (EPM) are well-recognized syndromes that are related to various conditions such as rapid correction of hyponatremia and chronic alcoholism. We report a very case of a patient with dysarthria, dysphagia and psychiatric symptoms including abnormal behavior starting after alcohol withdrawal, with radiological evidence of CPM and EPM. There was little improvement in the dysarthria or psychiatric symptoms in the first month.

Abnormal integrity of corticocortical tracts in mild cognitive impairment: a diffusion tensor imaging study.

Mild cognitive impairment (MCI) has been defined as a transitional state between normal aging and Alzheimer disease. Diffusion tensor imaging (DTI) can estimate the microstructural integrity of white matter tracts in MCI. We evaluated the microstructural changes in the white matter of MCI patients with DTI. We recruited 11 patients with MCI who met the working criteria of MCI and 11 elderly normal controls. The mean diffusivity (MD) and fractional anisotropy (FA) were measured in 26 regions of the brain with the regions of interest (ROIs) method. In the MCI patients, FA values were significantly decreased in the hippocampus, the posterior limb of the internal capsule, the splenium of corpus callosum, and in the superior and inferior longitudinal fasciculus compared to the control group. MD values were significantly increased in the hippocampus, the anterior and posterior limbs of the internal capsules, the splenium of the corpus callosum, the right frontal lobe, and in the superior and the inferior longitudinal fasciculus. Microstructural changes of several corticocortical tracts associated with cognition were identified in patients with MCI. FA and MD values of DTI may be used as novel biomarkers for the evaluation of neurodegenerative disorders.

Region-specific changes of cerebral white matter during normal aging: a diffusion-tensor analysis.

With aging, the human brain tissue undergoes degeneration and a decline in cognitive function. Diffusion tensor imaging (DTI) is a sensitive method for detecting microstructural changes of the brain white matter (WM). We examined the age-dependent, region-specific, changing patterns in microstructures of the brain. This was preformed by DTI analysis of 58 healthy volunteers from Korea. The fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were measured for each region of interest (ROI) in 22 areas. The FA and ADC values of all 22 ROIs were, respectively, compared among the age groups, by linear regression analysis and analysis of variance. With aging, the ADC values tended to increase and the FA values tended to decrease. Patterns of regional changes of the FA were divided into three subgroups. The cingulum was affected earliest with aging and the age-related WM changes show an anterior to posterior gradient acceleration throughout the decades tested. This study suggests that DTI is sensitive enough a diagnostic tool to detect subtle microstructural changes. These results show that the WM has a region-specific vulnerability to the aging process.