Wei-Ta Chen

Weight loss, nutritional status and physical activity in patients with Alzheimer’s Disease

Abstract.The etiology of weight loss in Alzheimer’s disease (AD) patients is still uncertain. This study was designed to investigate the possible factors that might contribute to weight change of AD patients. From July 1999 to June 2001, we recruited 51 AD patients and 27 non-demented controls. Demographic data, neuropsychological tests, Geriatric Depression Scale-Short Form, eating behavior questionnaire, dietary and physical activity diaries, anthropometric and laboratory measures of nutritional status were assessed. More than half of our AD patients developed body weight loss, and overall, the AD patients were significantly thinner than the non-demented subjects. Anthropometric and laboratory measures suggested a poorer nutritional status in the AD patients. The AD patients had fewer daily physical activities. More AD patients had the problem of poor appetite. However, daily calorie intake was not significantly different between the two groups. The AD patients, especially those who presented with body weight loss, even consumed more calories per body weight kilogram (kg) per day. In the food composition analysis, AD patients took more carbohydrate than controls. Multivariate regression analysis showed the existence of AD and poor appetite were the main risk factors of weight loss. We suggest that the pathophysiological process in AD gives rise to the changes of appetite and metabolic state in AD patients, and that these changes contribute to the weight loss.

Cutoff Scores of the Cognitive Abilities Screening Instrument, Chinese Version in Screening of Dementia

The purpose of this study of dementia screening was to obtain different cutoff scores of the Cognitive Abilities Screening Instrument, Chinese versions (CASI C-2.0) for subjects with different educational backgrounds. The diagnosis of dementia was based on the Diagnostic and Statistical Manual of Mental Disorders, ed 3 revised or ed 4 criteria. To diagnose Alzheimer’s disease, the guidelines of the National Institute of Neurological and Communicative Disorders and Stroke and Alzheimer’s Disease and Related Disorders Association was followed. The severity of dementia was determined on the Clinical Dementia Rating scale. Altogether 2,096 subjects, aged 65 years and more, were included. Of them, 1,178 were normal and 918 were demented. Their performance on CASI C-2.0 was influenced by their education and age. Gender difference on CASI C-2.0 scores was only significant in the illiterate, but not in the literate group. We recommend that the population be divided into three levels, namely those who (1) had no formal education (Edu = 0); (2) received 1–5 years of schooling (Edu = 1–5), and (3) received 6 or more years of education (Edu ≧6). The cutoff scores of CASI C-2.0 in the diagnosis of dementia in these three educational groups were as follows: Edu = 0: 49/50 (sensitivity = 0.83; specificity = 0.85); Edu = 1–5: 67/68 (sensitivity = 0.83; specificity = 0.91), and Edu ≧6: 79/80 (sensitivity = 0.89; specificity = 0.90).

Sustained visual cortex hyperexcitability in migraine with persistent visual aura.

Persistent aura without infarction, a rare migraine disorder, is defined by aura symptoms that persist for >1 week without radiological evidence of cerebral infarction. To unveil its pathophysiological mechanisms, this study used magnetoencephalography to characterize the visual cortex excitability in persistent aura by comparison with episodic and chronic migraine. We recruited six patients with persistent visual aura, 39 patients with episodic migraine [12 in ictal phase; 27 in interictal phase (with aura, n = 9; without aura, n = 18)], 18 patients with chronic migraine and 24 healthy controls. Five sequential blocks of 50 neuromagnetic prominent 100 ms responses were obtained, and the dynamic change in visual cortex excitability was evaluated by the percentage changes of individual mean prominent 100 ms amplitudes at blocks 2-5 compared with block 1, with a significant increase indicating potentiation. We found that in patients with persistent aura, there was significant potentiation during ictal periods (P = 0.009 and 0.006 at blocks 2 and 5, respectively), and the excitability change was inversely correlated with the duration of aura persistence (correlation coefficient -0.812, P = 0.050, block 2). The interictal recordings (n = 3) also showed potentiation. In terms of the other migraine spectrum disorders, persistent aura differed from episodic migraine in the presence of ictal potentiation. Persistent aura further differed from chronic migraine in the absence of interictal potentiation in chronic migraine. There was a higher percentage change of response amplitude at the end of stimulation (block 5) in persistent aura (43.3 ± 11.7) than in chronic migraine (-7.6 ± 5.5, P = 0.006) and ictal recordings of episodic migraine (-4.9 ± 9.6, P = 0.020). Normal control subjects had no significant response changes. This magnetoencephalographic study showed that the visual cortex in patients with persistent visual aura maintains a steady-state hyperexcitability without significant dynamic modulation. The excitability characteristic supports persistent visual aura as a nosological entity in migraine spectrum disorders and suggests a pathophysiological link to sustained excitatory effects possibly related to reverberating cortical spreading depression.

Functional Disability Profiles in Amnestic Mild Cognitive Impairment

Background/Aims: Instrumental activities of daily living (IADL) can be impaired in mild cognitive impairment (MCI), and the severity of functional disability predicts Alzheimer’s disease (AD) in amnestic MCI (aMCI). This study investigated the functional profiles of aMCI in a Chinese population. Methods: The Disability Assessment for Dementia scores of 56 subjects with single-domain aMCI (sd-aMCI) and 94 with multiple-domain aMCI (md-aMCI) were compared with normal controls (n = 64) and mild AD patients (n = 102). Results: Both the sd-aMCI (2.5 ± 2.5) and md-aMCI (3.7 ± 3.5) groups had more impaired IADL items than the controls (0.7 ± 1.7). Their IADL scores were intermediate, between the control and AD groups. sd-aMCI subjects presented deficits in 7 IADL items involving the ‘meal preparation’, ‘telephoning’, ‘finance’, ‘medications’, ‘housework’, and ‘leisure’ subscales. md-aMCI subjects presented deficits in 14 IADL items involving all subscales of daily activities. The Mini-Mental State Examination and Modified Trail-Making Test Part B scores were the major neuropsychological correlates of IADL performance in aMCI. Conclusion: IADL can be impaired in both sd-aMCI and md-aMCI. Including the functional ability assessment in the evaluation of aMCI may help clinicians to provide appropriate suggestions to maintain daily functioning.

Persistent ictal-like visual cortical excitability in chronic migraine

&NA; Episodic migraine (EM) may evolve into the more disabling chronic migraine (CM, monthly migraine days ⩾ 8 and headache days ⩾ 15) with unknown mechanism. Aiming to elucidate the pathophysiology of CM and its relationship with EM, this study characterized the visual cortical responses in CM and EM. Neuromagnetic visual‐evoked responses to left‐hemifield checkerboard reversals were obtained in patients with EM (interictal or ictal states), CM (interictal) and age‐matched controls. For each subject, the 1500 evoked responses were sequentially divided into 30 blocks and percentage changes of P100m amplitude in blocks 2, 9, 16, 23, and 30 compared to the first block were computed to assess habituation. At the end of visual stimulation (block 30), P100m amplitude was decreased (habituated) in the controls (n = 32) (35.2 ± 2.6 nAm vs. 41.9 ± 2.7, p = 0.005) but increased (potentiated) in the interictal state of EM (n = 29) (39.7 ± 3.8 vs. 33.5 ± 3.0, p = 0.007). In CM (n = 25), P100m was habituated (46.5 ± 2.9 vs. 51.6 ± 3.7, p = 0.013) but higher at the initial block than in those of the interictal state of EM (p = 0.001). These CM features also characterized the P100m in the ictal state of EM (n = 9). There was no difference of P100m between CM and ictal state of EM. In conclusion, patients with CM demonstrate a persistent ictal‐like excitability pattern of the visual cortex between migraine attacks which may implicate central inhibitory dysfunction.

Altered Oscillation and Synchronization of Default-Mode Network Activity in Mild Alzheimer’s Disease Compared to Mild Cognitive Impairment: An Electrophysiological Study

Some researchers have suggested that the default mode network (DMN) plays an important role in the pathological mechanisms of Alzheimer’s disease (AD). To examine whether the cortical activities in DMN regions show significant difference between mild AD from mild cognitive impairment (MCI), electrophysiological responses were analyzed from 21 mild Alzheimer’s disease (AD) and 21 mild cognitive impairment (MCI) patients during an eyes closed, resting-state condition. The spectral power and functional connectivity of the DMN were estimated using a minimum norm estimate (MNE) combined with fast Fourier transform and imaginary coherence analysis. Our results indicated that source-based EEG maps of resting-state activity showed alterations of cortical spectral power in mild AD when compared to MCI. These alterations are characteristic of attenuated alpha or beta activities in the DMN, as are enhanced delta or theta activities in the medial temporal, inferior parietal, posterior cingulate cortex and precuneus. With regard to altered synchronization in AD, altered functional interconnections were observed as specific connectivity patterns of connection hubs in the precuneus, posterior cingulate cortex, anterior cingulate cortex and medial temporal regions. Moreover, posterior theta and alpha power and altered connectivity in the medial temporal lobe correlated significantly with scores obtained on the Mini-Mental State Examination (MMSE). In conclusion, EEG is a useful tool for investigating the DMN in the brain and differentiating early stage AD and MCI patients. This is a promising finding; however, further large-scale studies are needed.

Visual cortex excitability and plasticity associated with remission from chronic to episodic migraine

Objective: Previous magnetoencephalographic (MEG) studies showed different P100m (where ‘m’ denotes the magnetic counterpart of P100 in conventional visual evoked potentials) responses between episodic migraine (EM) and chronic migraine (CM) interictally. This study investigated the changes of visual P100m in CM patients who remitted to EM from CM after treatment. Methods: At baseline, 25 patients with CM were studied interictally. For each patient, 30 sequential blocks of 50 P100m responses were obtained by MEG. Sub-averaged amplitudes at blocks 2, 9, 16, 23 and 30 were further compared with that at block 1 to assess response habituation or potentiation (i.e. significant decrease or increase at either block vs block 1). The same study was repeated in those patients who remitted from CM to EM after topiramate treatment. Results: In total, 10 CM patients remitted to EM after treatment. In the follow-up study of these patients during the interictal stage, the P100m at block 1 decreased in amplitude from 53.6 ± 6.6 nAm before remission to 43.0 ± 5.1 nAm (p = 0.028), and the responses at subsequent blocks switched from habituation (amplitude block 30 < block 1 before remission, p = 0.011) to potentiation (block 2 > block 1, p = 0.028). Conclusion: The pattern of P100m responses to consecutive stimulation changes with the transition from CM to EM. Visual cortex plasticity might be a potential biomarker reflecting clinical remission of CM.

Reduced cerebellar gray matter is a neural signature of physical frailty

Physical frailty has been recognized as a clinical syndrome resulting from declines in various physiological systems; however, the role of the central nervous system in the pathophysiology of frailty remains unclear. The I‐Lan Longitudinal Aging Study randomly sampled community‐dwelling people aged 50 or older for a brain magnetic resonance imaging study. All participants were assessed for frailty status (robust, prefrail, and frail) based on the presence of five frailty components: slow walking speed, muscle weakness, low physical activity, exhaustion and weight loss (Fried criteria). Gray matter volume (GMV) changes associated with frailty status and individual frailty components were examined. Overall, 456 participants (64.0 ± 8.5 years, 47.6% women) were included in this study. The prefrail (n = 178, 39.0%) and frail (n = 19, 4.2%) subjects were grouped for analysis. The prefrail–frail group showed reduced GMV, compared to the robust group (n = 259, 56.8%), in the cerebellum, hippocampi, middle frontal gyri, and several other cerebral regions (corrected P < 0.05). Each frailty component was associated with GMV changes in functionally related brain areas. Hierarchical cluster analysis categorized these components into three subsets. Motor‐related components, including weakness, low activity, and slowness, comprised one subset with a common cerebellar involvement. Exhaustion and weight loss were the other two subsets without cerebellar changes. To conclude, physical frailty is associated with a decreased reserve in specific brain regions, especially cerebellum. Further longitudinal studies are needed to explore if the cerebellum‐ and noncerebellum‐based frailty components reflect a distinctive future risk for developing frailty. Hum Brain Mapp 36:3666–3676, 2015.

Microscopic polyangiitis presenting with capsular warning syndrome and subsequent stroke

A 55-year-old man developed ischemic stroke after three episodes of transient dysarthria and left hemiplegia, a typical manifestation of capsular warning syndrome. Magnetic resonance imaging of the brain showed bilateral basal ganglionic infarction. The patient had no significant risk of stroke. However, the systemic manifestations, an elevated titer of perinuclear anti-neutrophilic cytoplasmic antibody and a skin biopsy revealing leukocytoclastic venulitis confirmed the undrlying microscopic polyangiitis.

ApoE 4 allele is associated with incidental hallucinations and delusions in patients with AD

Of 135 patients with Alzheimer disease (AD), 56 without psychiatric symptoms at the first visit were followed for a mean period of 51.9 ± 10.3 months to identify incident psychiatric symptoms. The hazard ratios of ApoE ε4 allele in developing psychiatric symptoms were calculated by Cox regression hazard analyses. The presence of the ApoE ε4 allele carried a 19.0-fold risk for developing hallucinations and a 3.4-fold risk for delusions.