Behavioral and psychological symptoms of dementia characteristic of mild Alzheimer patients

In order to clarify the characteristics of Behavioral and Psychological Symptoms of Dementia (BPSD) in patients with mild Alzheimer's disease (AD), BPSD among the severities of Clinical Dementia Rating (CDR) in 74 patients with AD were compared using the Neuropsychiatric inventory (NPI). The result, when compared between mild (CDR = 0.5, 1) and moderate or severe (CDR = 2, 3) AD, was a significant difference in frequency of euphoria, disinhibition and aberrant motor behavior, but no significant difference was found in frequency of delusions, hallucinations, agitation, dysphoria, anxiety, apathy and irritability. In addition, a significant difference was found in the mean scores of the composite score for euphoria, apathy, disinhibition and aberrant motor behavior, but no significant difference was found in the mean scores of the composite score for delusions, hallucinations, agitation, dysphoria, anxiety and irritability. That is, the mild AD groups (CDR 0.5 or 1) had delusions, hallucinations, agitation, dysphoria, anxiety, apathy and irritability as frequently as the moderate or severe AD groups (CDR 2 or 3), and had the equivalent level of composite scores to the moderate or severe AD groups (CDR 2 or 3) in delusion, hallucination, agitation, dysphoria, anxiety and irritability. Therefore, it was supposed that psychotic symptoms (delusion, hallucination) and emotional symptoms (agitation, dysphoria, anxiety, irritability) are important BPSD in patients with mild AD as well as those with moderate or severe AD, and there are needs for health, welfare and medical services for these symptoms.     

Neuropsychiatric symptoms in mild cognitive impairment: a population‐based study

Introduction: Few studies have examined neuropsychiatric symptoms in community dwelling older adults with mild cognitive impairment (MCI). In the present study, we compared the prevalence of neuropsychiatric symptoms in older adults with normal cognition, MCI, and dementia in a population‐based sample. Methods: Subjects were selected from the Singapore Longitudinal Ageing study. Normal cognitive function was defined as Clinical Dementia Rating (CDR) global score=0 and Mini‐Mental State Examination (MMSE) total score ≥24. MCI was defined as CDR global score=0.5, and dementia was defined as CDR global score ≥1. Neuropsychiatric Inventory (NPI) was administered on reliable informants for 293 subjects (136 normal, 133 MCI, and 24 dementia). Results: The prevalence of neuropsychiatric symptoms (at lest one symptom) was 5.9% for normal cognition, 12.8% for MCI, and 50% for dementia. The most common neuropsychiatric symptoms in subjects with MCI were depression/dysphoria (6.8%), irritability/lability (3.8%), apathy/indifference (2.3%), and agitation/aggression (2.3%). NPI total score increased with increasing CDR global score (P<0.001). The adjusted mean NPI total score was 0.07 (SEM=0.49) for normal cognition, 0.86 (SEM=0.46) for MCI, and 4.50 (SEM=0.82) for dementia. Discussion: In community dwelling Asian older adults, we found an increasing prevalence of neuropsychiatric symptoms in subjects with normal cognition, MCI and dementia. Further studies with larger samples and strict criteria for MCI in an Asian population should be conducted.     

De novo genesis of neuropsychiatric symptoms in mild cognitive impairment (MCI)

BACKGROUND: There is inadequate information regarding the neuropsychiatric aspect of Mild Cognitive Impairment (MCI). OBJECTIVE: To determine the neuropsychiatric profile of MCI, and compare this with normal controls and patients with mild Alzheimer's Disease (AD). DESIGN: Cross-sectional assessment of psychiatric symptoms in subjects that are enrolled in Mayo Clinic's longitudinal study of normal aging, MCI and dementia. METHODS AND PARTICIPANTS: The Neuropsychiatric Inventory (NPI) was administered to normal control subjects, MCI subjects and patients with early AD. Individual NPI domain scores and total NPI scores were compared among the three groups after controlling for age, educational status, Dementia Rating Scale (DRS) and Mini-Mental State Examination (MMSE) scores. Statistical analysis was performed by utilizing ANOVA, chi2 and Fisher's exact test. RESULTS: Data were analyzed on 514 normal controls, 54 MCI subjects, and 87 subjects with mild AD (CDR of 0.5 or 1); females consisted of 60.3%, 53.7% and 57.5%; and, the average ages (SD) were 77.8 (1.95), 79 (4.6), 80.5 (14.6) respectively. ANOVA pair-wise comparison revealed that both MMSE and DRS differences among the three groups were significantly different at (p = 0.05). The total NPI scores were significantly different (p =0.0001, F = 107.93) among the three groups using ANOVA. Pair-wise comparison of individual behavioral domain of NPI showed statistically significant differences between MCI and normals; and MCI and AD (p = 0.001). Group differences on NPI remained after controlling for age and education at p = 0.0375 and p = 0.0050 respectively. CONCLUSION: The neuropsychiatric pattern is reminiscent of the clinical, neuroimaging and neuropsychological profile of MCI. It gives further credence to the view that MCI is indeed the gray zone, with overlap on both ends of the pole.     

Efficacy of donepezil on behavioral symptoms in patients with moderate to severe Alzheimer's disease

OBJECTIVE: This subanalysis of a large, double-blind, placebo-controlled trial examined the prevalence of behavioral symptoms in moderate to severe Alzheimer's disease (AD), and the effect of treatment with donepezil. METHODS: Two hundred ninety patients with moderate to severe AD (standardized Mini-Mental State Examination scores 5-17) were randomized to receive 24 weeks of once-daily doses of donepezil 5 mg/day for 28 days, and 10 mg/day thereafter per the clinician's judgment (n = 144), or placebo (n = 146). The outcome measure of interest was the 12-item Neuropsychiatric Inventory (NPI). RESULTS: Baseline demographics were similar between the treatment groups. Least squares mean (+/- SE) baseline NPI 12-item total scores were 19.55 +/- 1.48 and 19.30 +/- 1.45, respectively. At baseline, the most common symptoms were apathy/indifference (67%), aberrant motor behavior (53%), depression/dysphoria (52%), anxiety (49%), and agitation/aggression (45%). NPI individual item change from baseline scores at Week 24 using a last observation carried forward (LOCF) analysis showed benefits with donepezil treatment compared with placebo for all items, with significant treatment differences for depression/dysphoria, anxiety, and apathy/indifference (p < .05). Symptoms present at baseline that improved significantly for donepezil- compared with placebo-treated patients at Week 24 LOCF included anxiety, apathy/indifference, and irritability/lability (p < .05). When patients who were not receiving psychoactive medications at baseline were analyzed separately, significant improvements in NPI (continued) 12-item total score were observed with donepezil compared with placebo at most visits and at Week 24 LOCF (p < .05). CONCLUSIONS: Behavioral symptoms of the magnitude observed in this moderate to severe AD population improved with donepezil.     

Neuropsychiatric symptoms in dementia-frequency, relationship to dementia severity and comparison in Alzheimer's disease, vascular dementia and frontotemporal dementia

Noncognitive behavioral and psychiatric disturbances are common in dementia and help in the clinical differentiation of the various subtypes. We studied the frequency of neuropsychiatric disturbances, their relationship to dementia severity and compared these disturbances in Alzheimer's disease (AD), vascular dementia (VaD) and frontotemporal dementia (FTD) using the 12-item Neuropsychiatric Inventory (NPI). A total of 98 patients (AD-44, VaD-31, FTD-23) were evaluated. All subjects were community dwelling at the time of evaluation. The three groups were comparable on global dementia severity and functional ability. All patients had clinically significant scores on the NPI with apathy, irritability and agitation being very common (>90% of patients). AD and VaD patients in Clinical Dementia Rating (CDR) stage 2 had significantly higher scores on the total NPI, agitation and disinhibition subscales compared to those in CDR stage 1. Mean scores in the domains of aberrant motor behavior, disinhibition and appetite/eating behavior differentiated FTD from AD and VaD. Neuropsychiatric disturbances in dementia appear to be universal with agitation, disinhibition and irritability being more frequent in the later stages. In this cohort disinhibition, aberrant motor behavior and appetite/eating disturbances could reliably differentiate AD and VaD from FTD. There were no significant differences between the neuropsychiatric profiles of AD and VaD.     

Neuropsychiatric symptoms in the community-based patients with mild cognitive impairment and the influence of demographic factors

OBJECTIVE: To investigate the pattern of neuropsychiatric symptoms of MCI patients in the Thai population and the influence of demographic factors on the symptoms. METHODS: One hundred and seven participants aged 50 and over diagnosed with MCI (n = 77) and normal (n = 30) were recruited from a community-based unit. The Neuropsychiatric Inventory (NPI) was used to assess behavioral disturbances in the subjects. RESULTS: Compared to normal subjects, MCI patients had higher incidence of anxiety (53% vs 27%, p = 0.013), dysphoria (46% vs 17%, p = 0.006), and sleep problem (45% vs 23%, p = 0.035). Although marginally significant, apathy was more common in MCI patients (12% vs 0%, p = 0.059). The mean total NPI score and NPI distress score were higher in the MCI group (6.8 vs 1.9, p < 0.0005 and 2.9 vs 0.6, p = 0.01, respectively). The MCI patients aged over 65 had higher incidence of hallucinations (18.9% vs 0%, p = 0.018). Males and patients of poor financial status had higher percentage of dysphoria compared to female and patients with better financial status (65% vs 38.5%, p = 0.041 and 75% vs 37.9%, p = 0.008, respectively). Patients with poor financial status also had higher percentage of anxiety (81.3% vs 44.5%, p = 0.01). CONCLUSIONS: MCI is associated with significant neuropsychiatric symptoms which caused caregiver distress. In this study, the pattern of neuropsychiatric symptoms in a Thai MCI population was similar to those reported in western countries. Age, sex, educational level and financial status influenced the neuropsychiatric symptoms of MCI patients.     

Efficacy of metrifonate in improving the psychiatric and behavioral disturbances of patients with Alzheimer's disease.

Neuropsychiatric and behavioral symptoms are frequent and problematic components of Alzheimer's disease (AD). In two previously reported studies, metrifonate was shown to benefit behavioral symptoms as assessed by the Neuropsychiatric Inventory (NPI). In this post hoc analysis, detailed studies were completed to determine the effects of metrifonate on individual symptoms. This study was a retrospective analysis of pooled NPI data from two double-blind, placebo-controlled, multicenter 26-week studies of metrifonate that had achieved similar levels of cholinesterase inhibition. Mild-to-moderate probable AD patients received placebo (n = 222) or metrifonate (n = 450) 30 to 60 mg by weight or a 50-mg fixed dose once daily. At 26 weeks, metrifonate-treated patients had significantly reduced NPI total scores (P = .001) and fewer neuropsychiatric symptoms when compared with placebo-treated patients, including hallucinations (P = .004), agitation/aggression (P = .006), depression/dysphoria (P = .011), apathy (P = .019), and aberrant motor behavior (P = .008). Metrifonate reduced or stabilized neuropsychiatric disturbances in 60% of symptomatic patients. Almost 40% of metrifonate-treated patients had a clinically relevant reduction (> or = 30% decrease in NPI score) in their neuropsychiatric disturbances (P = .002). High proportions of metrifonate-treated patients manifested clinically relevant reductions in anxiety (58%, P = .009), apathy (51%, P = .020), and depression/dysphoria (50%, P = .021) compared to placebo. The metrifonate-associated reductions in NPI scores were evident by week 12 and were maintained for the 26-week study period. There was an overall effect size of metrifonate of approximately 15% on total NPI scores when compared to placebo. Metrifonate significantly reduced many of the psychiatric and behavioral symptoms of AD. The observations suggest that enhancement of cholinergic functions in AD has beneficial effects on behavior.     

血管性痴呆精神行为学症状的相关因素分析

目的 了解血管性痴呆(VaD)患者的精神行为学症状特点及与认知障碍、年龄、受教育程度等因素的相关性,探讨神经精神科问卷(NPI)中不同因子之间的内在联系. 方法 采用NPI和简易智能状态检查量表(MMSE),分别评价120例VaD患者和61例健康老年人的精神行为学症状. 结果 VaD组患者NPI量表中的妄想、幻觉、激越、抑郁/心境恶劣、淡漠、易激惹、异常行为、食欲和饮食障碍等8个症状得分均明显高于正常对照组,差异有统计学意义(P＜0.05),其中得分最高的3个症状依次为抑郁/心境恶劣、情感淡漠、易激惹;其中幻觉、情感淡漠、异常行为等因子与认知障碍程度高度相关;异常行为与年龄、受教育程度均相关;同时对NPI各因子进行分析,获得了3个亚综合征,分别代表精神病性、情感异常和失控制行为. 结论 VaD患者普遍存在精神行为学症状,其症状的出现及严重程度与认知障碍、年龄、受教育程度有不同程度的相关性,各亚综合征中的子因子可能存在共同的病理生理基础.     

Anosognosia and neuropsychiatric symptoms and disorders in mild Alzheimer disease and mild cognitive impairment

Anosognosia is a multidimensional phenomenon that negatively affects course of illness. This study aimed to explore the association between anosognosia and neuropsychiatric phenomena in mild Alzheimer's disease (AD) and in mild cognitive impairment (MCI). The Anosognosia Questionnaire for Dementia to assess anosognosia, and the Neuropsychiatric Inventory to assess neuropsychiatric symptoms were administered to 209 patients (103 mild AD, 52 amnestic-MCI, and 54 amnestic multidomain-MCI). Categorical diagnoses of apathy, depression, and psychosis were made using specific criteria for dementia. With regard to continuous scores, in mild AD, we found positive correlation between symptoms of anosognosia and apathy, agitation and aberrant motor behaviors, while in MCI, we did not find significant association. At a categorical level, the diagnosis of anosognosia in mild AD was associated with the diagnosis of apathy. In mild AD, the frequent co-occurrence of frontally mediated behavioral disorders and anosognosia, particularly apathy, supports the hypothesis of a shared neuropsychogenic process due to the disruption of frontal brain networks.     

Neuropsychiatric Symptoms and Global Functional Impairment along the Alzheimer's Continuum

Background/Aims: Neuropsychiatric symptoms in Alzheimer's disease (AD) are highly prevalent. We sought to determine whether neuropsychiatric symptoms were related to global functional impairment at baseline and over a 3-year period in older normal control (NC), mild cognitive impairment (MCI) and mild AD dementia subjects. Methods: Eight hundred and twelve subjects (229 NC, 395 MCI, 188 AD) from the Alzheimer's Disease Neuroimaging Initiative study underwent cognitive and behavioral assessments over 3 years. Results: Greater hallucinations, anxiety and apathy were associated with greater global functional impairment at baseline, while the presence of hallucinations and apathy at baseline was associated with greater global functional impairment over time across all subjects. The following neuropsychiatric symptoms were not significantly associated with global functioning: delusions, agitation, depression, euphoria, disinhibition, irritability, aberrant motor behaviors, sleep and appetite. Conclusions: These results suggest that increased baseline hallucinations, apathy and anxiety are associated with current and future disease progression in AD.     

Neuropsychiatric symptoms are associated with progression from mild cognitive impairment to Alzheimer's disease

BACKGROUND: Neuropsychiatric disturbances are common in mild cognitive impairment (MCI). Depression and apathy may identify a subset of MCI subjects at higher risk of progression to Alzheimer's disease (AD). However, it remains uncertain whether a broader spectrum of psychopathology is associated with progression to AD. METHODS: Fifty-one MCI subjects were assessed for neuropsychiatric symptoms using the Neuropsychiatric Inventory. Subjects were followed for an average of 2 years. Twelve subjects (23.5%) progressed from MCI to possible/probable AD and 39 subjects (76.5%) remained stable or improved. Baseline Neuropsychiatric Inventory indices were compared between groups. RESULTS: Subjects progressing to AD had a significantly higher prevalence of psychopathology than subjects who remained stable or improved (100 vs. 59%). Depression (67 vs. 31%) and apathy (50 vs. 18%) were more common in subjects who were later diagnosed with AD. After statistical adjustments for other baseline demographic variables, these specific symptoms were less robust predictors of progression to AD than the presence of any psychopathology. CONCLUSIONS: These findings suggest that neuropsychiatric symptoms in MCI are a predictor of progression to AD. Depression and apathy appear to be most useful for identifying MCI subjects at highest risk of developing dementia.     

Behavioral symptoms in mild cognitive impairment

The authors investigated neuropsychiatric symptoms in mild cognitive impairment (MCI) from baseline data of the Investigation in the Delay to Diagnosis of AD with Exelon (InDDEx) study (n = 1,010). Neuropsychiatric symptoms were reported in 59% of subjects (Neuropsychiatric Inventory [NPI]). NPI+ subjects had significantly greater impairment on global, cognitive, and functional scores than NPI- subjects. The presence of neuropsychiatric symptoms appears to be a marker of MCI severity.     

Validity and reliability of the newly translated Hellenic Neuropsychiatric Inventory (H-NPI) applied to Greek outpatients with Alzheimer's disease: a study of disturbing behaviors among referrals to a memory clinic

CONTEXT: No rating scales of the neuropsychiatric symptoms of patients with dementia and Alzheimer's disease (AD) have previously been developed or translated. OBJECTIVES: To develop a Hellenic translation of the Neuropsychiatric Inventory (NPI), to evaluate it's reliability and validity, and to compare NPI results in Greek patients referred to a neuropsychiatry clinic for either of two reasons: disturbing behaviors evoking embarrassment and disturbing behaviors evoking fear in the caregiver. METHODS: The Hellenic translations of the NPI, Brief Psychiatric Rating Scale (BPRS), and Emotional Distress Scale (EDS) were compared in evaluating 29 consecutive referrals of patients with AD. RESULTS: The Hellenic NPI (H-NPI) demonstrated a high degree of internal consistency reliability, and of concurrent validity when compared to the BPRS or the EDS. Patients referred for behaviors evoking embarrassment presented with higher scores on NPI ratings of apathy. However, patients referred for behaviors evoking fear presented with higher scores on NPI ratings of aggression and irritability. CONCLUSIONS: These results indicate that the H-NPI is a reliable instrument, able to detect differences in clinically referred groups of AD patients.     

Neuropsychiatric symptoms in mild dementia with lewy bodies and Alzheimer's disease

Background/Aims: To compare neuropsychiatric symptoms in patients with Alzheimer's disease (AD) and dementia with Lewy bodies(DLB). Methods: Neuropsychiatric symptoms and caregiver distress were assessed using the Neuropsychiatric Inventory (NPI) in mild DLB (n = 57) and AD (n = 126), and compared across the two groups using non-parametric tests. Results: The DLB patients had a higher NPI totalscore (median 24 vs. 11.5, p < 0.005), more numerous symptoms (median 5 vs. 4, p = 0.001) and more clinically significant symptoms (3 vs. 1, p = 0.001). They also had higher item hallucinations (6 vs. 2, p < 0.005) and apathy (7 vs. 5, p = 0.002) subscores. Caregivers scored higher on the NPI total caregiver distress scale (12.5 vs. 6, p = 0.003). Conclusions: In mild dementia, DLB patients have more neuropsychiatric symptoms and more associated caregiver distress compared with AD.     

Neuropsychiatric symptoms and functional status in Alzheimer's disease and vascular dementia patients

Neuropsychiatric symptoms (NPS) are increasingly recognized as common in patients with dementia, both of degenerative (Alzheimer's disease, AD) or vascular origin (vascular dementia, VaD). In this study, 302 demented patients, 166 with AD and 136 with VaD, were evaluated for NPS according to the Neuropsychiatric Inventory (NPI) score at the Alzheimer's Evaluation Unit of Casa Sollievo della Sofferenza Hospital-IRCCS, San Giovanni Rotondo, Italy. A comprehensive geriatric assessment was also performed in all demented patients. The means of NPI scores did not differ in two groups. The overall prevalence of NPS was similar in both groups of patients (69.7% vs. 69.4%). Patients with AD had higher frequency in agitation/aggression and irritability/lability than VaD patients. Logistic analysis demonstrated a significant association between severity of the cognitive impairment and depression and eating disorders in both AD and VaD patients. The association with agitation/aggression, irritability/lability, and aberrant motor activity was found in AD only, and with apathy in VaD patients only. In both AD and VaD patients, there was a significant association between the impairment in activities of daily living (ADL) and the majority of NPI domains. A significant association was also found between the impairment of the instrumental activities of daily living (IADL) and agitation/aggression, anxiety, aberrant motor activity in AD and depression, apathy, irritability/lability, sleep disturbance and eating disorders in both AD and VaD patients. In particular, a causal mediation analysis was performed to better understand whether the relationship of NPS to functional impairment was direct or mediated by severity of cognitive dysfunction, i.e., Clinical dementia rating scale (CDR) score. Only agitation/aggression was mediated by the CDR score in affecting ADL status in VaD patients (OR: 1.12, 95% CI: 1.01-1.27). The NPI-Distress scores showed a significantly higher levels of distress in caregivers of AD than VaD. There were significant differences between AD and VaD patients with NPS, and these symptoms varied according to dementia subtype and severity and induced marked disability in ADL and IADL, increasing, prevalently, the distress of the caregivers of AD patients.     

康奈尔痴呆抑郁量表中文版的信度检测及临床应用研究

目的：检测康奈尔痴呆抑郁量表中文版（CSDD-CV）的信度，并对AD患者抑郁的相关因素进行研究。方法：对60例阿尔茨海默病（AD）患者及其照料者进行调查，了解患者访视前1周的症状和体征。结果：CSDD-CV的Cronbach’s α系数为0．810，5个因子的Cronbach’s α系数在0．576--0．788。CSDD-CV的平均得分为6．84（0-21）分，CSDD．CV≥8分21例（36．84％）。除第12项外，CSDD-CV各项目与总分的相关系数在0．273-0．782，P均〈0．05。CSDD-CV与NPI总分的相关系数为0．631，P〈0．05，与NPI子项目A妄想、C激越、D抑郁、G情感淡漠、I易激惹、J异常行为及K睡眠均具有显著相关性，P均〈0．05。采用多元线性逐步回归分析发现AD患者出现抑郁的影响因素主要为IADL和NPI。结论：CSDD．CV具有良好的信度和效度，可以用于AD患者抑郁状态的评定，同时AD抑郁状态可能与患者精细的日常生活能力有关，而与认知功能的下降无关。     

Quality of Life in relation to neuropsychiatric symptoms in Alzheimer's disease: 5‐year prospective ALSOVA cohort study

Objective

To examine the association between neuropsychiatric symptoms (NPS) with self‐ and caregiver‐rated Quality of Life (QoL) for patients with Alzheimer's disease (AD) during a 5‐year follow‐up.

Methods

The ALSOVA 5‐year follow‐up study included, at baseline, 236 patients with either very mild (Clinical Dementia Rating Scale (CDR) 0.5), or mild (CDR 1) AD, together with their caregivers from three Finnish hospital districts. QoL was evaluated using patient self‐reported, and caregiver‐rated, QoL in AD (QoL‐AD) scores. NPS were assessed using the Neuropsychiatric Inventory (NPI), and AD severity was evaluated using the CDR, with cognition tested by the mini‐mental state examination. The performance of daily activities was assessed using the Alzheimer's Disease Cooperative Study–Activities of Daily Living Inventory.

Results

Over the 5‐year follow‐up period, patient self‐reported QoL‐AD scores did not change significantly (p = 0.245), despite increases in their NPS. However, caregiver‐rated patient QoL‐AD scores declined significantly (p ≤ 0.001), as total NPI scores increased during follow‐up. No NPS at baseline, and only apathy at follow‐up, correlated significantly (p = 0.007) with patient self‐rated QoL‐AD scores. Caregiver‐rated patient QoL‐AD scores correlated significantly with most NPS, especially (p ≤ 0.001) apathy, agitation, anxiety, irritability, depression, and delusions at baseline, and delusions, hallucinations, apathy, appetite disturbances, and anxiety during follow‐up.

Conclusions

Patient rated QoL‐AD scores are an unreliable tool with which to evaluate the success of therapy for NPS. Instead, caregiver‐rated scores for patients correlated well with NPI scores, and health care professionals in the clinic should preferentially use these. Copyright © 2017 John Wiley & Sons, Ltd.     

Plasma level of chitinase 3-like 1 protein increases in patients with early Alzheimer’s disease

Previously, chitinase 3-like 1 (CHI3L1) protein level was increased in various inflammatory conditions and cancers. This study was aimed to evaluate the plasma CHI3L1 level as a potential prognostic biomarker for Alzheimer’s disease (AD). Forty-nine patients with mild cognitive impairment (MCI), 61 patients with mild to severe AD, and 35 healthy elderly controls were recruited for this study. They were given a comprehensive neuropsychological test battery including a mini-mental status examination (MMSE), clinical dementia rating (CDR), and neuropsychiatric inventory (NPI). The CHI3L1 levels were measured using a specific enzyme-linked immunosorbent assay in the plasma and cerebrospinal fluid (CSF). A significant increase in the mean plasma level of CHI3L1 was found in early AD patients compared to control subjects and MCI patients. No significant difference was found between MCI patients and controls. There was a significant positive correlation between CHI3L1 levels and neuropsychological test scores such as CDR and NPI in MCI and early AD patients. Our results demonstrate that CHI3L1 plasma levels are elevated in early AD compared to control or MCI patients. Thus, CHI3L1 plasma levels may be useful as a biomarker, reflecting disease severity in AD patients.     

Neuropsychiatric differences between Parkinson's disease with dementia and Alzheimer's disease

OBJECTIVE: To compare the profile of neuropsychiatric symptoms in patients with Parkinson's disease with dementia (PDD) and patients with Alzheimer's disease (AD). DESIGN: Cross-sectional survey of a population-based sample of patients with PDD and AD patients matched for age, sex, and Mini-Mental State Examination (MMSE) score. METHOD: Patients were diagnosed according to published criteria for PD and AD. The diagnosis of dementia in PD was made according to DSM-III-R, and was based on clinical interview of the patient and a relative, psychometric testing (including MMSE, Dementia Rating Scale and tests assessing memory, executive functions and visuospatial functioning) and physical examination. The Neuropsychiatric Inventory (NPI) was administered to all patients. RESULTS: One or more psychiatric symptoms was reported in 95% of AD and 83% of PDD patients. Hallucinations were more severe in PD patients, while aberrant motor behavior, agitation, disinhibition, irritability, euphoria, and apathy were more severe in AD. In PDD, apathy was more common in mild Hoehn and Yahr stages, while delusions increased with more severe motor and cognitive disturbances. In PDD, only delusions correlated with the MMSE score. CONCLUSIONS: Neuropsychiatric symptoms are common and severe in patients with PDD, with important implications for the management of these patients. AD and PDD patients have different neuropsychiatric profiles, suggesting different underlying mechanisms. Cognitive impairment, psychopathology, and motor features progress independently in PDD patients Copyright 2001 John Wiley & Sons, Ltd.     

Psychiatric phenotype of the fragile X-associated tremor/ataxia syndrome (FXTAS) in males: newly described fronto-subcortical dementia

OBJECTIVE: The authors describe and quantify the neuropsychiatric symptoms present in a cohort of males with the fragile X mental retardation 1 (FMR1) premutation allele who have developed fragile X-associated tremor/ataxia syndrome (FXTAS). METHOD: Fourteen male carriers of the FMR1 premutation who had clinical manifestations of the FXTAS syndrome and 14 age- and education-matched controls were assessed with the Neuropsychiatric Inventory (NPI), formal cognitive testing, and genetic analysis. RESULTS: Males with FXTAS had significantly higher total NPI scores (p < .004) and significantly higher scores on the agitation/aggression (p < .004), depression (p < .004), apathy (p < .004), disinhibition (p < .004), and irritability (p < .004) scales, compared with controls. Cognitive performances on the Mini-Mental State Examination did not correlate with severity of symptoms on the NPI. CONCLUSIONS: The neuropsychiatric manifestations of FXTAS, based on this preliminary report, appear to cluster as a fronto-subcortical dementia. Clinicians encountering patients with clinical dementia with motor symptoms suggesting FXTAS should consider genetic testing to determine whether the patient's dementia syndrome is secondary to a fragile X premutation carrier status.