认知功能筛查量表在MCI和轻度AD患者中的应用

目的:探讨认知功能筛查量表在轻度认知功能损害(Mild Cognitive Impairment,MCI)和轻度阿尔茨海默病(Alzhei mer disease,AD)患者中的应用。方法:对61例MCI患者和47例轻度AD患者进行系列神经心理学测验,同时选择41例正常老年人做对照。结果:MCI组和正常老年人比较,MGR、MMSE的短时记忆亚项、FOM、LM、DR、CDT均有统计学差异。轻度AD组和MCI组比较,MMSE的即刻记忆亚项、RVR、DS、ADL、IADL、POD均有统计学差异。CES-D在三组间无统计学差异。结论:MGR量表可用来鉴别正常人和认知功能损害人群,但不宜用来鉴别MCI和轻度AD患者。RVR和DS量表可以用于鉴别MCI和轻度AD患者。ADL量表在轻度AD患者显示损害,提示AD患者存在日常生活行为能力的损害。     

Patient versus informant reported quality of life in the earliest phases of Alzheimer's disease

OBJECTIVES: The study investigated if patient and informant reported Quality of Life (QoL) differed in early Alzheimer's disease (AD). In addition, we examined whether anosognosia had an impact on the agreement between patient and informant ratings of QoL and whether anosognosia, dementia severity, depression and behavioural symptoms were significantly correlated to QoL in early AD. METHODS: From a prospective research program including newly referred patients (age >60 years and MMSE > or = 20), 48 patients with very early AD were included. QoL was assessed using the QoL-AD and EQ-5D scales. Anosognosia was rated on a categorical scale by an examiner. MMSE, Geriatric Depression Scale, Danish Adult Reading Test and Frontal Behavioural Inventory were also administered. RESULTS: On most QoL measures patients rated their QoL higher than their informants. Anosognosia was not associated with QoL but significantly with an inverse impact on the agreement between patient and informant ratings of QoL. Self-reported QoL was significantly correlated to depression but not to age, dementia severity, behavioural symptoms or memory impairment. Informant ratings of QoL were significantly correlated to behavioural symptoms and informant ratings on the EQ-5D Visual Analogue Scale were significantly correlated to patient reported depression. CONCLUSION: Patients with early AD generally reported higher QoL than their informants. This disagreement was associated with the presence of anosognosia. Self-reported QoL did not correlate with the MMSE score. Behavioural changes and depressive symptoms may be associated with low QoL.     

Alzheimer病和轻度认知功能障碍患者认知功能与局部脑血流灌注的相关性研究

目的研究Alzheimer病(AD)和轻度认知功能障碍(MCI)患者的认知功能与脑血流灌注的相关性。方法33例AD、17例MCI患者分别接受临床评估、神经心理学检查[包括简易精神状态检查法(MMSE)及临床记忆量表(CMS)]后进行单光子发射计算机断层(SPECT)检查。应用SPSS 10.0软件对神经心理学指标与脑血流灌注指标进行相关性分析。结果MMSE评分与双侧颞顶叶放射性计数值(RAR)呈正相关,MQ值与左颞叶、左丘脑RAR呈正相关。结论认知功能与脑血流灌注之间有良好相关性,二者结合可更客观地评价脑功能改变,提高判定疾病的准确性。     

Frontal Behavioural Inventory in the differential diagnosis of dementia

Objective –  To evaluate diagnostic properties of the Frontal Behavioural Inventory (FBI) in patients suffering from different forms of dementia.
Methods –  The FBI was administered with other psychometric tests investigating cognitive performances and behavioral scales to the caregivers of 35 patients with the frontal variant of frontotemporal dementia (fv-FTD), 22 patients with Alzheimer's disease (AD) and 15 with vascular dementia (VaD). All patients were comparable for degree of dementia severity and level of executive impairment.
Results –  The FBI showed high concurrent validity, internal consistency and good inter-rater and test–retest reliability. The discriminant validity was also very high. A new FBI cut-off score of 23 gave 97% sensitivity and 95% specificity in distinguishing fv-FTD from non-FTD patients. Conversely, the Neuropsychiatic Inventory (NPI) score was unable to differentiate fv-FTD from AD.
Conclusions –  The FBI is a neurobehavioral tool suitable to distinguish fv-FTD from other forms of dementia also when data from cognitive testing or other behavioral scales fail to support the differential diagnosis.     

Functional connectivity variations in mild cognitive impairment: associations with cognitive function

Participants with mild cognitive impairment (MCI) have a higher likelihood of developing Alzheimer's disease (AD) compared to those without MCI, and functional magnetic resonance neuroimaging (fMRI) used with MCI participants may prove to be an important tool in identifying early biomarkers for AD. We tested the hypothesis that functional connectivity differences exist between older adults with and without MCI using resting-state fMRI. Data were collected on over 200 participants of the Rush Memory and Aging Project, a community-based, clinical-pathological cohort study of aging. From the cohort, 40 participants were identified as having MCI, and were compared to 40 demographically matched participants without cognitive impairment. MCI participants showed lesser functional connectivity between the posterior cingulate cortex and right and left orbital frontal, right middle frontal, left putamen, right caudate, left superior temporal, and right posterior cingulate regions; and greater connectivity with right inferior frontal, left fusiform, left rectal, and left precentral regions. Furthermore, in an alternate sample of 113, connectivity values in regions of difference correlated with episodic memory and processing speed. Results suggest functional connectivity values in regions of difference are associated with cognitive function and may reflect the presence of AD pathology and increased risk of developing clinical AD.     

Three-dimensional gray matter atrophy mapping in mild cognitive impairment and mild Alzheimer disease

BACKGROUND: Alzheimer disease (AD) is the most common form of dementia worldwide. Mild cognitive impairment (MCI) is the recent terminology for patients with cognitive deficiencies in the absence of functional decline. Most patients with MCI harbor the pathologic changes of AD and demonstrate transition to dementia at a rate of 10% to 15% per year. Patients with AD and MCI experience progressive brain atrophy. OBJECTIVE: To analyze the structural magnetic resonance imaging data for 24 patients with amnestic MCI and 25 patients with mild AD using an advanced 3-dimensional cortical mapping technique. DESIGN: Cross-sectional cohort design. Patients/ METHODS: We analyzed the structural magnetic resonance imaging data of 24 amnestic MCI (mean MMSE, 28.1; SD, 1.7) and 25 mild AD patients (all MMSE scores, >18; mean MMSE, 23.7; SD, 2.9) using an advanced 3-dimensional cortical mapping technique. RESULTS: We observed significantly greater cortical atrophy in patients with mild AD. The entorhinal cortex, right more than left lateral temporal cortex, right parietal cortex, and bilateral precuneus showed 15% more atrophy and the remainder of the cortex primarily exhibited 10% to 15% more atrophy in patients with mild AD than in patients with amnestic MCI. CONCLUSION: There are striking cortical differences between mild AD and the immediately preceding cognitive state of amnestic MCI. Cortical areas affected earlier in the disease process are more severely affected than those that are affected late. Our method may prove to be a reliable in vivo disease-tracking technique that can also be used for evaluating disease-modifying therapies in the future.     

Cognitive decline and amyloid accumulation in patients with mild cognitive impairment

Background/Aims: The relationship between baseline (11)C-Pittsburgh compound B ((11)C-PIB) uptake and cognitive decline during a 2-year follow-up was studied in 9 patients with mild cognitive impairment (MCI) who converted to Alzheimer's disease (AD) and 7 who remained with MCI. Methods: (11)C-PIB PET scan was conducted at baseline and cognitive assessment both at baseline and at follow-up. To obtain quantitative regional values of (11)C-PIB uptake, automated region of interest analysis was done using spatially normalized parametric ratio (region-to-cerebellar cortex) images. Results: At baseline, there were statistically significant differences in (11)C-PIB uptake, but not in cognitive test performances between the converters and nonconverters. Memory and executive function declined only in the converters during follow-up. In the converters, lower baseline frontal (11)C-PIB uptake was associated with faster decline in verbal learning. Higher baseline uptake in the caudate nucleus was related to faster decline in memory consolidation, and higher temporal uptake was associated with decline in executive function. Conclusion: Higher (11)C-PIB uptake in the caudate nucleus and temporal lobe was related to decline in memory and executive functions, whereas lower frontal uptake was related to decline in verbal learning. The results indicate that in prodromal AD, frontal amyloid accumulation reaches its maximum in the MCI stage, characterized by memory problems without full-blown dementia.     

Confabulation, but not executive dysfunction discriminate AD from frontotemporal dementia

We examined confabulation and performance on frontal/executive tasks in Alzheimer's disease (AD) patients and patients with a diagnosis of probable frontotemporal dementia (FTD). Twenty-two patients with probable AD, 10 patients with probable FTD and 32 normal control subjects entered the study. Executive functions were assessed with the Modified Card Sorting test; a verbal fluency test; the Cognitive Estimation test; and the Stroop test. Confabulations were assessed with a modified version of the Confabulation Battery. The Confabulation Battery included 10 questions tapping each of the following domains: Episodic Memory (memories of personal past episodes), Semantic Memory (knowledge of famous facts and famous people), and Personal Future (personal plans). The results revealed that both AD patients and FTD patients were clearly and equally impaired on tests of executive functions. Both patients' groups confabulated across the three tasks of the Confabulation Battery, but FTD patients confabulated significantly more than AD patients on Episodic Memory and Personal Future. The results failed to provide any evidence of a correlation between the performance on frontal/executive tasks and the tendency to produce confabulatory reports. According to our results, confabulation, more than a deficit of frontal/executive functions, discriminate between AD and FTD. Therefore, screening for confabulation and, possibly, for other types of memory distortions may constitute a useful additional clinical tool in order to discriminate AD from FTD.     

The Frontal Behavioural Inventory (Italian version) differentiates frontotemporal lobar degeneration variants from Alzheimer's disease

Abstract The objective was to evaluate the construct validity of the Italian version of the Frontal Behavioural Inventory (FBI) and its usefulness in the differential diagnosis of dementias. Standard criteria were used in the clinical diagnosis of dementias in 83 patients and 33 agematched healthy volunteers. The FBI scale was translated from English into Italian language and back-translated. Cronbach's alpha, inter-rater and test-retest reliability, FBI convergent validity and discriminant analysis were calculated. FBI profile was compared between patients affected by frontotemporal lobar degeneration (FTLD) and Alzheimer's disease (AD). The FBI showed a high internal consistency and inter-rater reliability and it distinguished normal behavioural conditions from those presented in FTLD or AD. An 86.8% diagnostic accuracy was calculated by the discriminant analysis, selecting only age at disease onset and FBI, and particularly distinguishing behavioural variants within the FTLD spectrum. FTLD patients showed a characteristic behavioural profile. The FBI might be a reliable and useful diagnostic tool for dementias in clinical practice.     

Regional cerebral blood flow measured by99mTc-HMPAO SPECT differs in subgroups of Alzheimer's disease

Summary Alzheimer's disease (AD) is a heterogeneous entity. Identifying AD subtypes might have impact in patients' response to different treatment strategies. We designed a study to examine regional cerebral blood flow (rCBF) in AD subtypes. To identify AD subtypes, we performed a cluster analysis including performance on memory, language, visuospatial, praxis, and executive functions. The rCBF measured by^99mTc-HMPAO SPECT was referred to the cerebellum. We examined 35 patients fulfilling the NINCDS-ADRDA criteria of probable AD and 13 age and sex-matched healthy cognitively intact controls. AD patients were at the early stage of the disease, their mean Mini-Mental Status (MMS) score (S.D.) was 22.5 (3.6). The cluster analysis revealed two AD subgroups: AD1 (N=12) and AD2 (N=23). The subgroups did not differ in age, sex, or global clinical severity as assessed by MMS and Brief Cognitive Rating Scale (BCRS). Both subgroups had equally impaired memory. The AD2 group was inferior to the AD1 group on verbal, visuospatial, praxic, and executive functions. The AD1 group showed reduced rCBF ratios in the temporal and parietal cortices and the amygdala compared to controls. The AD2 group differed from controls in the rCBF ratios of frontal, temporal, parietal, occipital, basal ganglia, and amygdaloid regions bilateral and from AD1 in the rCBF ratios of frontal and temporal cortices. In AD patients, the rCBF ratios did not correlate with MMS or BCRS scores. In contrast, several significant correlations were found between decreases rCBF ratios and impairment of memory and other cognitive functions. In conclusion, a cluster analysis on neuropsychological test performance identified two AD subgroups that differed on the neuropsychological profile and on the rCBF in spite of similar global clinical severity.     

Japanese version of the Test Your Memory as a screening test in a Japanese memory clinic

A self-administered cognitive test (Test Your Memory, TYM) is designed as a screening test for the detection of Alzheimer disease (AD). We compared the diagnostic utility of the Japanese version of the TYM (TYM-J) in AD and mild cognitive impairment (MCI) with that of the Mini-Mental State Examination (MMSE) and Alzheimer's Disease Assessment Scale—Cognitive Subscale Japanese version (ADAS-Jcog). We studied 79 patients with mild AD, 46 with MCI and 34 normal controls. The sensitivity and specificity of each test in the diagnosis of AD and MCI were compared. The average total TYM-J scores were 45.7 in controls, 41.7 in MCI, and 35.7 in AD. The TYM-J scores showed good correlations with other neuropsychological tests. The receiver operating characteristic analysis demonstrated that the TYM-J could better discriminate AD from controls and MCI from controls than the other tests. With each optimal cut-off score of the TYM-J, the sensitivity and specificity were 96% and 91% for diagnosing AD, and 76% and 74% for diagnosing MCI, respectively. The TYM-J is useful for the diagnosis of AD and MCI, and can be applied as a screening test in a Japanese memory clinic.     

The frontal assessment battery does not differentiate frontotemporal dementia from Alzheimer's disease

BACKGROUND: An early differentiation of Alzheimer's disease (AD) from frontotemporal dementia (FTD) is important, since these conditions are essentially different regarding prognosis and therapeutical approach. Until now, no single test is available which allows a reliable differentiation. The Frontal Assessment Battery (FAB) has been found to have good reliability in identifying an executive deficit in frontal syndromes and in extrapyramidal disorders. The ability of the FAB to distinguish AD from FTD in mildly demented patients is less clearly assessed. METHODS: We compared FAB scores in a consecutive series of 33 FTD (frontal variant) and 85 AD patients. RESULTS: FAB global scores in the two groups were very similar, also when considering only mildly demented subgroups [Mini Mental State Examination (MMSE) score > or = 20; 20 FTD and 38 AD patients]. Considering FAB subscores, only the 'go-no go' subtest showed a significant difference, reflecting a poorer inhibitory motor control in AD patients. FAB scores in the two groups of patients correlated with global cognitive decline (MMSE), and with executive and visuospatial test scores, showing good concurrent validity. CONCLUSION: The FAB does not differentiate patients with AD from those with FTD, like all other executive tests. However, it may be useful in the examination of executive function in AD, FTD and several other pathological conditions.     

Behavioral quantitation is more sensitive than cognitive testing in frontotemporal dementia

OBJECTIVE: To compare behavioral and cognitive testing in the clinical diagnosis of frontotemporal dementia (FTD). METHODS: A clinically defined cohort of FTD (n = 52) is compared with 52 Alzheimer disease (AD) patients on a Frontal Behavioral Inventory (FBI) and cognitive tests (e.g., Mini-Mental State Examination, Mattis Dementia Rating Scale, Western Aphasia Battery, Wechsler Intelligence Scale, Wechsler Memory Scale). Fourteen patients with FTD had autopsy confirmation, and their tests are also compared with the rest of the FTD population. RESULTS: The FTD and AD groups were matched in sex, duration, and severity of dementia. The total scores on the FBI showed the largest difference. Mini-Mental State Examination and Mattis Dementia Rating Scale total scores did not discriminate between the two groups. Memory subscores were lower in the AD group, and conceptualization and language-related scores were worse in the FTD group. Milder and earlier affected patients, who could carry on a large battery of neuropsychological tests, were much better distinguished by the FBI scores on discriminant function analysis. In contrast to 78% by the cognitive tests, 98% of the FTD and AD patients were differentiated by the FBI. CONCLUSIONS: Although memory scores were lower in AD and language scores in the FTD population, many of the cognitive tests do not distinguish between FTD and AD. On the other hand, a behavioral inventory is a useful adjunct in the diagnosis of FTD. Postmortem validation was carried out in a sizeable subset of the population, showing similar behavioral and cognitive data.     

Differences in Cognitive Profile between TIA, Stroke and Elderly Memory Research Subjects: A Comparison of the MMSE and MoCA

Background: The Montreal Cognitive Assessment (MoCA) appears more sensitive to mild cognitive impairment (MCI) than the Mini-Mental State Examination (MMSE): over 50% of TIA and stroke patients with an MMSE score of ≥27 ('normal' cognitive function) at ≥6 months after index event, score <26 on the MoCA, a cutoff which has good sensitivity and specificity for MCI in this population. We hypothesized that sensitivity of the MoCA to MCI might in part be due to detection of different patterns of cognitive domain impairment. We therefore compared performance on the MMSE and MoCA in subjects without major cognitive impairment (MMSE score of ≥24) with differing clinical characteristics: a TIA and stroke cohort in which frontal/executive deficits were expected to be prevalent and a memory research cohort. Methods: The MMSE and MoCA were done on consecutive patients with TIA or stroke in a population-based study (Oxford Vascular Study) 6 months or more after the index event and on consecutive subjects enrolled in a memory research cohort (the Oxford Project to Investigate Memory and Ageing). Patients with moderate-to-severe cognitive impairment (MMSE score of <24), dysphasia or inability to use the dominant arm were excluded. Results: Of 207 stroke patients (mean age ± SD: 72 ± 11.5 years, 54% male), 156 TIA patients (mean age 71 ± 12.1 years, 53% male) and 107 memory research subjects (mean age 76 ± 6.6 years, 46% male), stroke patients had the lowest mean ± SD cognitive scores (MMSE score of 27.7 ± 1.84 and MoCA score of 22.9 ± 3.6), whereas TIA (MMSE score of 28.4 ± 1.7 and MoCA score of 24.9 ± 3.3) and memory subject scores (MMSE score of 28.5 ± 1.7 and MoCA score of 25.5 ± 3.0) were more similar. Rates of MoCA score of <26 in subjects with normal MMSE ( ≥27) were lowest in memory subjects, intermediate in TIA and highest after stroke (34 vs. 48 vs. 67%, p < 0.001). The cerebrovascular patients scored lower than the memory subjects on all MoCA frontal/executive subtests with differences being most marked in visuoexecutive function, verbal fluency and sustained attention (all p < 0.0001) and in stroke versus TIA (after adjustment for age and education). Stroke patients performed worse than TIA patients only on MMSE orientation in contrast to 6/10 subtests of the MoCA. Results were similar after restricting analyses to those with an MMSE score of ≥27. Conclusions: The MoCA demonstrated more differences in cognitive profile between TIA, stroke and memory research subjects without major cognitive impairment than the MMSE. The MoCA showed between-group differences even in those with normal MMSE and would thus appear to be a useful brief tool to assess cognition in those with MCI, particularly where the ceiling effect of the MMSE is problematic.     

A retrospective study of the behavioural and psychological symptoms of mid and late phase Alzheimer's disease

AIM: To document the behavioural and psychological symptoms in patients with a diagnosis of established Alzheimer's disease (AD) for at least 3 years. METHODS: Patients with a > or =3 year history of AD (NINCDS/ADRDA) were recruited from old age psychiatrist and elderly care memory clinics. Information regarding duration of symptoms and non-cognitive symptomatology was obtained during interview with a carer or next-of-kin who had contact with the patient at least 3 times a week and for at least 3 years. MMSE, FAST and NPI including caregiver distress, were used to assess cognition, function and behavioural/psychological disturbance respectively. With each non-cognitive symptom the carer was asked to estimate its onset. RESULTS: The mean age of patients was 77 years and duration of illness 87 months. Mean MMSE was 8/30 and FAST score 6d. Of the psychological symptoms occurring at any stage, depression (56%), delusions (55%) and anxiety (52%) were most common, with hallucinations, elation and disinhibition occurring less frequently. In general, behavioural changes were more common with apathy occurring in 88% of patients, motor behaviour in 70%, aggression in 66%, irritability and appetite changes in 60% and sleep disturbance in 54%. All symptoms except apathy became less common when the carer was asked if they were still present in the last month. Mean onset of psychological symptoms was 47 months. Mean onset of behavioural symptoms was 48 months. Behavioural disturbance seemed to cause more care-giver distress than psychological change. CONCLUSION: The results show behavioural and psychological symptoms in AD are common and distressing for carers. They appear to require a consistent period of neurodegeneration in order to emerge.     

Delusions increase functional impairment in Alzheimer's disease

Background/Aims: Delusions in Alzheimer's disease (AD) may be associated with functional impairment. No studies to date have used functional instruments sensitive to changes in frontal executive function, possibly underestimating the impact. Methods: Patients with AD with and without delusions were administered cognitive tests and questionnaires to assess depression and quality of life. Caregivers were administered questionnaires to assess functional impairment, caregiver burden and behavioural symptoms. Results: AD patients with delusions (n = 19) when compared to AD patients without delusions (n = 19) matched for age, education and global cognitive function were significantly more functionally impaired based on performance on the Disability Assessment for Dementia Scale (p < 0.005). Conclusion: AD patients with delusions have significantly worse functional performance.     

Anosognosia in very mild Alzheimer's disease but not in mild cognitive impairment

OBJECTIVE: To study awareness of cognitive dysfunction in patients with very mild Alzheimer's disease (AD) and subjects with mild cognitive impairment (MCI). METHODS: A complaint interview covering 13 cognitive domains was administered to 82 AD and 79 MCI patients and their caregivers. The patient groups were comparable according to age and education, and Mini Mental State Examination (MMSE) scores were > or =24 in all cases. The discrepancy between the patients' and caregivers' estimations of impairments was taken as a measure of anosognosia. RESULTS: Self-reports of cognitive difficulties were comparable for AD and MCI patients. However, while in comparison to caregivers MCI patients reported significantly more cognitive impairment (p < 0.05), AD patients complained significantly less cognitive dysfunctions (p < 0.001). CONCLUSIONS: While most MCI patients tend to overestimate cognitive deficits when compared to their caregiver's assessment, AD patients in early stages of disease underestimate cognitive dysfunctions. Anosognosia can thus be regarded as a characteristic symptom at a stage of very mild AD (MMSE > or =24) but not MCI. Accordingly, medical history even in mildly affected patients should always include information from both patient and caregiver.     

Screening for cognitive impairment: a triage for outpatient care

The current increase in aged individuals in number and proportion of the general population warrants dependable strategies to improve early detection of cognitive impairment. It was the goal of the present study to develop a triage for bedside testing and outpatient services. In a prospective clinical cohort study at the outpatient Memory Clinic, University of Ulm, Germany, 232 subjects were diagnosed with Alzheimer's disease [AD; NINCDS-ADRDA criteria; n = 66; age 65.9 +/- 7.3 years (mean +/- SD); Mini Mental State Examination (MMSE) score 23.4 +/- 4.1], mild cognitive impairment (MCI; criteria of Petersen et al.; n = 48; age 66.4 +/- 7.1 years; MMSE score 28.3 +/- 1.5), and major depressive disorder (DSM-IV criteria; n = 61; age 63.4 +/- 8.0 years; MMSE score 28.6 +/- 1.6). Diagnosis was secured with extensive neuropsychological, clinical, radiological, and laboratory investigations. Six brief screening tests including the Memory Impairment Screen (MIS), Letter Sorting Test (LST), Verbal Fluency (VF), and Clock Drawing Test (CDT) were assessed independently from the diagnostic procedure. We compared single items and composite scores. LST yielded a diagnostic accuracy of 0.81 and 0.62 for AD and MCI patients versus controls, respectively. With the MIS, diagnostic accuracy was 0.89 and 0.71, respectively. With a combination of LST, MIS, VF, and CDT, a sensitivity for AD and MCI patients of 1.00 and 0.83 was achieved. Thus, single-item screening (e.g. LST, VF) taking little more than 1 min and suitable for bedside testing or brief screening in the general practitioner's office yields diagnostic accuracy comparable to standard laboratory tests for other diseases. A composite of screening tests suitable for application in general outpatient care in neurological and psychiatric services reliably detects patients with AD and MCI.     

SPECT Follow-Up Study of Cerebral Blood Flow Changes During Donepezil Therapy in Patients with Alzheimer''s Disease

BACKGROUND AND PURPOSE: Treatment with acetylcholinesterase inhibitors (AchEIs) is beneficial for patients with Alzheimer's disease (AD). But the clinical response varies. Functional neuroimaging techniques might allow objective evaluation of the topographic correlates of the effect of therapy on brain functioning. We attempted to evaluate the possible correlation between regional cerebral blood flow (rCBF) differences in patients with AD and response to donepezil hydrochloride (Donepezil) therapy. METHODS: The subjects of this study were 51 consecutive patients with AD receiving Donepezil who underwent SPECT at baseline and 10-14 months later. We divided the patients into stabilized (n = 19) and nonstabilized (n = 32) subgroups based on changes in the Mini Mental State Examination (MMSE) score. Analysis of single-photon emission computed tomography (SPECT) data was done using 3-dimensional stereotactic surface projections (3D-SSP) and the stereotactic extraction estimation (SEE) method. We compared differences in rCBF between the two subgroups at baseline and follow-up, and between the baseline and follow-up in each subgroup. RESULTS: Significant correlation was recognized between the mean Z score changes of the left frontal lobe, left limbic lobe, and MMSE change. There were no significant baseline differences in rCBF in any region of the brain between the two subgroups. At the study endpoint, the nonstabilized subgroup showed lower rCBF in the lateral and medial frontal lobes, limbic lobe, lower lateral temporal lobe, and cingulate gyrus compared to the stabilized subgroup. Both patient groups showed a significant post-treatment increase over baseline values in the frontal lobe, and the stabilized group had more extensive and intense increases in the lateral and medial frontal lobes and orbital surface. CONCLUSIONS: Our study suggests that the diversity of clinical responses to Donepezil therapy in patients with AD is associated with rCBF changes, mainly in the frontal lobe. SPECT may be a promising tool to assess the impact of AchEI therapy on the brain function of patients with AD.     

Brief informant screening test for mild cognitive impairment and early Alzheimer's disease

BACKGROUND/AIMS: Recent research has attempted combinations of instruments to improve screening accuracy for mild cognitive impairment (MCI) and early Alzheimer's disease (AD). We compared Mini-Mental State Examination (MMSE), Immediate and Delayed Recall (Logical Memory I and II; LM-I and LM-II, respectively), a single-item informant report of memory problem (IRMP), and a four-item Instrumental Activities of Daily Living (4IADL) scale, and combinations of these tests. METHOD: The tests were administered together with Clinical Dementia Rating (CDR) to subjects who were cognitively intact (CDR = 0, n = 88), and with diagnoses of MCI (CDR = 0.5, n = 37) and early AD (CDR = 1-2, n = 19). RESULTS: Screening accuracy (receiver operating characteristic area under curve, AUC) for identifying MCI or MCI-AD was lowest for MMSE (AUC 67.6% for MCI or 77.9% for MCI-AD), and better for IRMP (79.5 or 83.2%), 4IADL (76.9 or 84.7%), LM-I (81.2 or 87.1%) and LM-II (86.1 or 90.8%). Combining IRMP, 4IADL and LM-II was most accurate (AUC 91.7% for MCI or 94.5% for MCI-AD); sensitivity: 86.5 or 89.3%; specificity: 86.4 or 88.6%. However, combining IRMP and 4IADL gave nearly as good accuracy (AUC 87.2 or 91.6%); sensitivity: 86.5 or 85.7%; specificity: 79.5 or 85.2%. CONCLUSION: A brief instrument combining an IRMP and 4IADL items is potentially useful in screening for MCI and early AD.