Ching-Kuan Liu

Apolipoprotein E polymorphism and behavioral and psychological symptoms of dementia in patients with Alzheimer disease.

The aims of this study were to identify subsyndromes of behavioral and psychological symptoms of dementia (BPSD) in Alzheimer disease (AD), and to investigate whether the apolipoprotein E (ApoE) gene confers a risk of distinct BPSD subsyndromes. BPSD of 96 patients with AD were assessed using the Neuropsychiatric Inventory. Factor analysis with principal component analysis and varimax rotation was used to construct the BPSD subsyndromes. ApoE genotypes were determined using the TaqMan technology. The results showed that the 5 subsyndromes can be determined, including: agitation/aggression-delusion, euphoria-disinhibition, depression-apathy, hallucination-nighttime behavior, and appetite. ApoE &egr;4 carriers had higher factor scores in the agitation/aggression-delusion subsyndrome. We demonstrated that ApoE &egr;4 confers a higher risk for the subsyndrome of agitation/aggression delusion in AD.

Plasma concentration of donepezil to the therapeutic response of Alzheimer's disease in Taiwanese.

Donepezil has been approved for the treatment for mild-to-moderate Alzheimers disease (AD), but the therapeutic response rate varies from 20 to 60%. A higher oral dosage was suggested to have a better therapeutic response in reported results, but the plasma concentration of donepezil was not examined with respect to the therapeutic outcomes in those studies. Therefore, we analyzed the therapeutic responses, measured by neuropsychological assessments, among 70 newly diagnosed AD patients taking donepezil (5 mg daily) in relation to their plasma concentration of donepezil, apolipoprotein E genotype, and demographic characteristics. Our results have showed 60% of recruited AD patients improved in cognition, measured by Mini-Mental Status Examination (MMSE), and 57.1% in global status, by Clinical Dementia Rating Scale (CDR) sum of boxes (CDR-SB). In cognition, compared to the improving group, the clinically worsening group had a significantly higher donepezil concentration [p = 0.022, odds ratio (OR) = 1.024, 95% CI = 1.003-1.045] and higher initial MMSE score (p = 0.007, OR = 1.330, 95% CI = 1.080-1.639). In global status, initially higher CDR-SB (p = 0.028, OR = 2.318, 95% CI = 1.096-4.903) and initially higher MMSE (p = 0.036, OR = 1.201, 95% CI = 1.012-1.425), not donepezil concentration (p = 0.883), were significantly associated with clinical worsening. Our results have indicated that the dosage of donepezil should be reconsidered for AD patients, especially those clinically worsening in cognition.

Adjunct effect of music therapy on cognition in Alzheimer’s disease in Taiwan: a pilot study

Purpose Music therapy (MT) reviews have found beneficial effects on behaviors and social interaction in Alzheimer’s disease (AD) but inconsistent effects on cognition. The purpose of the study was to evaluate the adjunct effect of long-term and home-based MT in AD patients under pharmacological treatment. Patients and methods Mild AD cases (clinical dementia rating =0.5~1) were consecutively recruited and voluntarily separated into an MT group or control group (CG) for 6 months. Outcome assessments included Cognitive Abilities Screening Instrument (CASI), CASI-estimated mini-mental state examination, clinical dementia rating with sum of box scores, and neuropsychiatric inventory. The MT interventions were Mozart’s Sonata (KV 448) and Pachelbel’s Canon, listening with headphones for 30 minutes daily in the morning and before sleep, respectively. Results Forty-one cases (MT versus CG number =20 versus 21) were analyzed. Adjusted differences of CASI-estimated mini-mental state examination and CASI after 6 months in the MT group were slightly less decreased than the CG without statistical significance. In further analysis of cognitive domains of CASI, the adjusted difference of abstraction domain in the MT group was significantly better than the CG. Conclusion Although there were no apparent additional benefits of this MT on the global cognition and daily functioning in mild AD patients, it confirms the adjunct cognition effect on the abstraction. This MT contributes to the supplementary treatment of AD.

Plasma Homocysteine Levels and Major Depressive Disorders in Alzheimer Disease

BACKGROUNDnThe main aim of this study was to examine the symptomatology of major depression in Alzheimer disease (AD) and its relationship with plasma homocysteine level.nnnMETHODSnEighty-three patients with AD were enrolled for clinical assessments and examination of fasting plasma homocysteine. Diagnosis of major depression was made, and the severity of the depression was assessed.nnnRESULTSnThe moderate dementia patients presented with more common behavioral disturbances related to major depression than mild dementia patients. Major depression in patients with moderate AD was associated with higher plasma homocysteine levels. Furthermore, a high plasma homocysteine level was positively associated with behavioral disturbance among study participants with major depression.nnnCONCLUSIONnMore behavioral disturbance associated with major depression occurred as the dementia progressed. Patients with a higher level of plasma homocysteine presented with a higher behavioral disturbance symptomatology. This finding may account for the relationship between elevated homocysteine levels and depression only in patients with moderate AD.

The Psychiatric Manifestation of Creutzfeldt-Jakob Disease

Creutzfeldt-Jakob disease (CJD) is considered to be very rare in the population, and the psychiatric manifestation of the disease even rarer with only one report in the past few years in Taiwan. To clarify whether the psychiatric manifestation of CJD is really rare or whether it is neglected in Taiwan, the authors reviewed the discharge notes of patients who had been admitted to a neurological unit in the past 15 years and conducted a chart review of the patients of CJD supported by the clinical courses, EEG finding and brain biopsies. An inquiry was made by telephoning their families to follow up their condition after discharge. Five of the 8 cases with CJD had psychiatric symptoms including changes of mood, thought, behavior and perception during their course of illness. Four cases had been sent to the psychiatric unit and received treatment under several kinds of psychiatric diagnoses. Two patients had been admitted to the psychiatric unit and one had received electroconvulsive treatment. Two of the patients had been suspected to be the victims of neuroleptic malignant syndrome. It is likely that it is psychiatrists who will meet CJD patients first in the early stages of disease. CJD should be kept in mind and EEGs with detailed neurological checkups should be completed, if the cognitive functions of the patients with unusual neurological symptoms deteriorate quickly and their psychiatric symptoms fail to respond to any treatment.

Hypothyroid Myopathy-Pathological and Ultrastructural Study

Seventeen patients with hypothyroid myopathy were studied before and after thyroxine (T4) treatment. The severity of clinical myopathy was assessed with the aid of a modified rating scale. Laboratory findings including thyroid function, serum creatine kinase (CK), and electromyography were assessed at regular time intervals until a final muscle biopsy was performed. The average period of follow-up was 1.8 years. The authors emphasize: 1) in skeletal muscle pathology of hypothyroidism, the fiber atrophy and increased central nuclear counts are evidence of clinical myopathy during thyroxine treatment; 2) in ultrastructural pathology, the abnormal glycogen accumulation accounts largely for clinical severity and its ongoing resolution is parallel to steady amelioration following T4 therapy, while mitochondrial abnormalities are insignificant in clinical correlation and probably become permanent in some cases with prolonged hypothyroidism; and 3) serial needle biopsies of skeletal muscle are impractical for long-term study of hypothyroid myopathy, but they may be reserved for those patients with a sustained myopathic complaints on T4 therapy.

Concentrations of rivastigmine and NAP 226-90 and the cognitive response in Taiwanese Alzheimer's disease patients.

The aim of this small pilot study was to evaluate the association between plasma concentrations of rivastigmine and its metabolite, NAP 226-90, and cognitive function in patients with Alzheimers disease (AD). Rivastigmine-treated AD patients, who had been maintained on a fixed regimen of twice daily rivastigmine (6 to 12 mg/d) for ≥6 months, were eligible for evaluation. The assessments included cognitive assessment screening instrument (CASI) and clinical dementia rating scale, conducted at baseline and at 6-month follow-up. The 9 subdomains of CASI at baseline and follow-up were analyzed in relation to the plasma concentrations of rivastigmine and NAP 226-90, as measured by capillary electrophoresis. Logistic regression was performed to adjust for age, gender, education level, apolipoprotein E ε4 genotype status, and baseline CASI score to investigate the association between plasma rivastigmine and NAP 226-90 concentrations and the cognitive response. The total sample consisted of 53 clinically diagnosed AD patients taking rivastigmine only at doses of 6 mg to 9 mg/d because of intolerability at 12 mg/d. Higher rivastigmine concentration was significantly associated with improved or preserved short-term memory and worsened abstraction/judgment (p < 0.05), but not with changes in other domains (p > 0.05). Higher NAP 226-90 concentration was significantly associated with worsened abstraction/judgment (p < 0.05), but not with changes in other domains. Higher plasma rivastigmine concentration was significantly associated with improved or preserved short-term memory but worsened abstraction/judgment. An optimal concentration of rivastigmine should be quantified for each patient because of differential cognitive responses.

Effects of metabolic syndrome, apolipoprotein E, and CYP46 on cognition among Taiwanese Chinese.

The combined effects of metabolic syndrome and the apolipoprotein E and CYP46 genotypes on the risk of cognitive decline has yet to be determined among Taiwanese Chinese. Two hundred and nine mentally healthy middle‐aged and older adults were assessed for metabolic syndrome, cognitive function using the Cognitive Abilities Screening Instrument, Mini‐Mental State Examination, ApoE, and CYP46 polymorphisms. There were no differences in cognitive performance, ApoE epsilon4 (ε4) carrier status, or CYP46 genotypes between participants with and those without metabolic syndrome. The ε4 carriers and participants with the AA allele of CYP46 had significantly lower mental manipulation score. Metabolic syndrome and ε4 had synergistic effects on cognitive decline. Therefore, the ε4 carriers and participants with the AA allele of CYP46 have decreased mental manipulation ability. The metabolic syndrome may play a role in subtle cognitive dysfunction in ε4 carriers among Taiwanese Chinese.

A study of central and peripheral nerve conduction in patients with primary hypothyroidism: the effects of thyroxine replacement.

Somato-Sensory Evoked Potential (SSEP) and Peripheral Nerve Conduction (PNC) studies were performed in twenty patients with primary hypothyroidism to elucidate the changes of central and peripheral nervous systems in hypothyroid state and the effects of thyroxine replacement. Before thyroxine replacement therapy, eleven patients had significantly delayed SSEP (prolonged latencies of N9, N13, or N20), and only three patients had prolonged central conduction time (between N13 and N20). PNC abnormalities with decreased conduction velocity and diminished amplitudes were found in fourteen patients. After thyroxine treatment, both SSEP and PNC studies demonstrated significant improvement and paralleled the clinical neurological amelioration. The central and peripheral conduction velocities returned to normal limits, while the abnormality in amplitude still persisted. There were also discrepancies between SSEP and PNC studies in both the abnormality pattern and the recovery potential. Our observations may suggest: firstly, both the SSEP and PNC studies may be useful, alternative tools in monitoring the neurological disorders in hypothyroidism; and secondly, the pathogenesis of central and peripheral nervous dysfunction in hypothyroidism may be via different mechanisms.

Action-Monitoring Dysfunction in Obstructive Sleep Apnea - A Pilot Study

Obstructive sleep apnea (OSA) is associated with a broad range of frontal lobe dysfunctions. However, no study has investigated action monitoring, a crucial domain of frontal cognitive functions, in patients with OSA. By using the modified Flanker task, we tested the hypothesis that patients with OSA have an impaired action monitoring function. We recruited 25 untreated patients with moderate–severe OSA and 12 control participants who were matched for age, sex, apolipoprotein E4, and education level. Every enrolled participant underwent a standard overnight laboratory-based polysomnography and completed a modified Flanker task. Compared with the controls, the patients with OSA presented a significantly lower correct response rate in all trials (78.9% vs 95.9%, P = .008), congruent trials (84.7% vs 98.3%, P = .016), and incongruent trials (77.4% vs 94.7%, P = .009). The post-error correction rate was significantly lower in the patients with OSA than in the controls (74.9% vs 93.8%, P = .005). Furthermore, strong significant correlations were observed between the arousal index and correct rate in all trials (r = −0.390, P < .05) and in the incongruent trials (r = −0.429, P < .01), as well as between the arousal index and rate of post-error correction (r = −0.435, P < .01). We concluded that the action monitoring function was impaired in the patients with OSA. Sleep fragmentation was a major determinant of impaired action monitoring in these patients.