Patterns of Word-List Generation in Mild Cognitive Impairment and Alzheimer's Disease

Patients with amnestic mild cognitive impairment (aMCI) have been described as exhibiting greater impairment on tests of category fluency than letter fluency. This has been offered as evidence that this condition represents pre-clinical Alzheimer's disease (AD). We hypothesized that this pattern of differential impairment is dependent on the specific semantic categories and initial letters selected, and is not specific to AD and aMCI. A total of 40 cognitively normal older adults, 74 MCI patients—25 “amnestic single domain” (aMCI), 27 “amnestic multiple domain”, and 22 non-amnestic—and 29 AD patients were tested with multiple forms of semantic-category and initial-letter fluency tasks. The pattern of deficits within and across groups was highly dependent on the specific categories and letters chosen. Overall, aMCI patients did not demonstrate greater impairment in category than letter fluency. In fact, the level and pattern of their performance resembled that of cognitively normal older adults much more than AD patients. MCI patients with deficits in multiple cognitive domains performed most like AD patients. These findings indicate that verbal fluency performance is highly influenced by the specific tasks used, and impairment on semantic fluency is not characteristic of pure amnestic MCI.     

阿尔茨海默病嗅觉障碍的研究

目的 :研究阿尔茨海默病 (AD)患者嗅觉障碍。方法 :配对的AD患者和正常老年人各 3 0例 ,分别行简易智能状态检查(MMSE)、日常生活活动量表 (ADL)、图片识别试验、气味感知阈值、图片介导的气味识别试验及气味再认记忆试验检查。结果 :AD组的气味感知、气味识别和气味再认记忆功能较正常对照组差 (P <0 0 1) ;相关分析显示 ,AD组患者的嗅觉障碍与MMSE总分密切相关 (P <0 0 5 ) ;结论 :AD患者的嗅觉功能全面受损 ,嗅觉障碍是疾病的早期症状 ,是认知障碍的简单反映     

The profile of executive functioning in amnestic mild cognitive impairment: disproportionate deficits in inhibitory control

Amnestic mild cognitive impairment (aMCI) represents a group of individuals who are highly likely to develop Alzheimer's disease (AD). Although aMCI is typically conceptualized as involving predominantly deficits in episodic memory, recent studies have demonstrated that deficits in executive functioning may also be present, and thorough categorization of cognitive functioning in MCI may improve early diagnosis and treatment of AD. We first provide an extensive review of neuropsychology studies that examined executive functioning in MCI. We then present data on executive functioning across multiple sub-domains (divided attention, working memory, inhibitory control, verbal fluency, and planning) in 40 aMCI patients (single or multiple domain) and 32 normal elderly controls (NECs). MCI patients performed significantly worse than NECs in all 5 sub-domains, and there was impairment (>1.0 SD below the mean of NECs) in all sub-domains. Impairment on each test was frequent, with 100% of MCI patients exhibiting a deficit in at least one sub-domain of executive functioning. Inhibitory control was the most frequently and severely impaired. These results indicate that executive dysfunction in multiple sub-domains is common in aMCI and highlights the importance of a comprehensive neuropsychological evaluation for fully characterizing the nature and extent of cognitive deficits in MCI.     

Odor identification in mild cognitive impairment subtypes

The current study examined odor identification using the Brief Smell Identification Test (BSIT) in mild cognitive impairment (MCI) subtypes (17 "amnestic MCI", 46 "amnestic-plus MCI", and 25 "MCI other"). Performance in participants with MCI was compared to that of participants with Alzheimer's disease (AD, n=44) and healthy elderly (n=21). MCI participants performed worse than controls, but better than those with AD. MCI subtypes did not differ. The magnitude of difference between MCI participants and controls was modest, raising some question of the clinical utility of the BSIT in early detection of MCI and early differential diagnosis.     

Behavioral regulation: factor analysis and application of the Behavioral Dyscontrol Scale in dementia and mild cognitive impairment

BACKGROUND: Executive dysfunction is a hallmark of both Dementia of the Alzheimer's Type (AD) and Vascular Dementia (VaD). A complete neuropsychological battery contains measures of executive function, but the focus tends to be on cognitive processes with verbal or written output. The Behavioral Dyscontrol Scale (BDS) is purported to be a measure of executive function that addresses control over voluntary motor behavior. Previous factor analyses revealed three-factor solutions using a variety of patient populations. Our goals were to examine the factor structure in a sample of geriatric outpatients and to apply that factor structure to detect possible differences between AD, VaD, amnestic Mild Cognitive Impairment (MCI), non-amnestic MCI, and normal controls. METHODS: An exploratory factor analysis was performed on 260 outpatient evaluations from 2002-2006. Only the seven items requiring motor responses were included. RESULTS: A two-factor solution emerged. We named the factors Motor Problem-Solving and Simple Motor Repetitive Behaviors. For the first factor, the AD and VaD groups differed from the MCI groups and normal controls, but did not differ from each other. There were no differences between the control, amnestic MCI, and non-amnestic MCI groups. There were no differences between the groups for the second factor. CONCLUSION: It was concluded that voluntary control of behavior that requires problem-solving for complex tasks may help differentiate dementia from mild cognitive impairment and normal aging.     

Multiple cognitive deficits in amnestic mild cognitive impairment

OBJECTIVE: To determine if more widespread cognitive deficits are present in a narrowly defined group of patients with the amnestic form of mild cognitive impairment (MCI). METHODS: From a larger sample of patients clinically diagnosed as meeting the criteria of Petersen et al. for amnestic MCI, we selected 22 subjects who had Clinical Dementia Rating scores of zero on all domains besides memory and orientation. These MCI subjects with presumably isolated memory impairments were compared to 35 age-matched normal controls and 33 very mild Alzheimer's disease (AD) patients on a battery of neuropsychological tests. RESULT: In addition to the expected deficits in episodic memory, the amnestic MCI group performed less well than the controls but better than the AD group on design fluency, category fluency, a set shifting task and the Stroop interference condition. Over half the amnestic MCI group (vs. none of the normal controls) scored at least 1 standard deviation below control means on 4 or more of the nonmemory cognitive tasks. CONCLUSIONS: Isolated memory impairment may be fairly uncommon in clinically diagnosed amnestic MCI patients, even when the criteria for amnestic MCI are fairly narrow. Additional cognitive impairments are likely to include fluency and executive functioning. These more diffuse deficits argue for comprehensive cognitive assessments, even when the patient and family are reporting only memory decline, and are consistent with the increase in attention paid to the heterogeneity of MCI.     

Nonepisodic memory deficits in amnestic MCI.

OBJECTIVE: To (a) compare patients with amnestic Mild Cognitive Impairment (MCI), mild Alzheimer disease (AD), and a group of healthy elderly persons on nonepisodic memory measures; (b) examine which measures are independent of level of education in the groups studied. BACKGROUND: Episodic memory impairment is a cardinal feature of preclinical AD. However, a number of other cognitive measures are also sensitive to the preclinical stage of AD and deficits in multiple domains characterize AD several years before clinical diagnosis. MATERIALS AND METHODS: Patients with amnestic MCI (N=31), patients with mild probable AD (N=15), and healthy elderly controls (N=27) were compared on nonepisodic memory tasks measuring fluid intelligence, working memory, processing speed, verbal fluency, and visual-perceptual and motor functions. Amnestic MCI patients were selected based on clinical criteria and a subgroup was also selected based on psychometric criteria. RESULTS: Multivariate analyses of covariance, controlling for the effects of age, education, and sex, showed that fluid intelligence, working memory, processing speed, semantic fluency, visual-perceptual function, and complex motor function were significantly worse in the MCI than the elderly control group. Working memory, processing speed, semantic fluency, and complex motor tasks were significantly worse in the mild probable AD than the MCI group. The analyses were corroborated using the psychometrically derived MCI group. CONCLUSIONS: (a) Performance on multiple nonepisodic memory measures is affected in the preclinical stage of AD, indicating that broad cognitive impairment characterizes that stage. (b) Complex motor tasks were independent of level of education in our sample, and may have practical utility in the early detection of dementia.     

Loss of awareness of hyposmia is associated with mild cognitive impairment in Parkinson's disease

BackgroundHyposmia is a common non-motor symptom in Parkinson's disease (PD). However, patients with PD are sometimes unaware of their olfactory dysfunction, resulting in an under-diagnosis of this symptom. To determine whether the loss of awareness of hyposmia results from cognitive impairment in patients with PD, we investigated the relationship between the degree of hyposmia self-awareness and the cognitive status of non-demented PD patients.MethodsThirty-one non-demented patients with PD and 20 healthy controls (HC) were assessed via a self-reported olfactory questionnaire and an odor identification test. PD patients were sub-classified as having mild cognitive impairment (PD-MCI) or as cognitively normal (PD-CN) (according to the current PD-MCI criteria). We compared the degree of hyposmia self-awareness between the PD-MCI and PD-CN groups.ResultsThe PD-MCI group scored the lowest on the odor identification test among all groups, whereas PD-MCI patients tended to rate their olfactory function higher on the self-reported olfactory questionnaire than PD-CN patients. Differences in the scores of subjective and objective olfactory measures between the PD-MCI and PD-CN groups were significant (p = 0.0069).ConclusionsThe loss of awareness of hyposmia is closely associated with mild cognitive impairment (MCI) in PD patients.     

Three-dimensional patterns of hippocampal atrophy in mild cognitive impairment

OBJECTIVE: To measure hippocampal volumes in patients diagnosed as having subtypes of mild cognitive impairment (MCI) relative to those of elderly control subjects and those of patients with Alzheimer disease (AD) using 3-dimensional mesh reconstructions. DESIGN: A magnetic resonance imaging volumetric study of MCI subgroups (MCI, amnesic subtype [MCI-A]; and MCI, multiple cognitive domain subtype) using 3-dimensional mesh reconstructions of the structure. SETTING: Referral dementia clinic. SUBJECTS: Twenty-six subjects with MCI (MCI-A, n = 6; and MCI, multiple cognitive domain subtype, n = 20), 20 subjects with AD, and 20 controls who were equivalent in age, education, and sex distributions. MAIN OUTCOME MEASURES: Three-dimensional parametric mesh models of the hippocampus and total hippocampal volumes. RESULTS: The hippocampi of the patients with AD were significantly atrophic relative to those of the healthy controls. The MCI, multiple cognitive domain subtype, group did not differ from the controls, yet was significantly different from the MCI-A and the AD groups. The MCI-A patients had significant hippocampal atrophy compared with the controls, and did not differ significantly from the patients with AD. CONCLUSION: These data add to the growing evidence that there are multiple forms of MCI, that they have distinct neuropathological correlates, and that MCI, multiple cognitive domain subtype, is not a more advanced form of the MCI-A subtype.     

Olfactory identification in non-demented elderly population and in mild cognitive impairment: a comparison of performance in clinical odor identification versus Boston Naming Test

Performance in olfactory identification was studied in mild cognitive impairment (MCI), using slightly expanded standard clinical approach to study the olfactory nerve. Four hundred and eighty-six cognitively normal individuals and 72 individuals with MCI underwent spontaneous and cued odor identification and delayed odor recall. Performance in these was compared with the performance in the CERAD version of the Boston Naming Test (BNT). The individuals with MCI scores significantly worse in all tests compared with controls, but the performance in tests assessing odor were less impaired than performance in the BNT. Standard assessment of olfactory nerve function is not sufficient to study cognitive impairment in MCI.     

Defining mild cognitive impairment in Parkinson's disease

Our purpose was to characterize a state of mild cognitive impairment (MCI) in Parkinson's disease (PD) (PD‐MCI) that would be analogous to the MCI that is posited as a precursor of Alzheimer's disease (AD). We categorized 86 PD subjects in a brain bank population as either cognitively normal (PD‐CogNL), PD‐MCI using criteria that included a 1.5 standard deviation or greater deficit upon neuropsychological testing consistently across at least one cognitive domain without dementia, and PD dementia (PD‐D) using DSM‐IV criteria. Twenty‐one percent of our PD sample met criteria for PD‐MCI, 62% were PD‐CogNL, and 17% had PD‐D. The mean duration of PD and MMSE scores of the PD‐MCI group were intermediate and significantly different from both PD‐CogNL and PD‐D. The cognitive domain most frequently abnormal in PD‐MCI was frontal/executive dysfunction followed by amnestic deficit. Single domain PD‐MCI was more common than PD‐MCI involving multiple domains. We conclude that a stage of clinical cognitive impairment in PD exists between PD‐CogNL and PD‐D, and it may be defined by applying criteria similar to the MCI that is posited as a precursor of AD. Defining PD‐MCI offers an opportunity for further study of cognitive impairment in PD and targets for earlier therapeutic intervention. © 2007 Movement Disorder Society     

A clinical memory battery for screening for amnestic mild cognitive impairment in an elderly chinese population

Amnestic mild cognitive impairment (MCI) might be more likely to progress to Alzheimer’s disease than single non-memory MCI and multiple domain MCI. After excluding those who did not conform to the inclusion criteria of amnestic MCI or healthy controls, a neuropsychologic battery that included the Mini-Mental State Examination, Clinical Dementia Rating, Chinese version of the Montreal Cognitive Assessment, Instrumental Activities of Daily Living scale and Auditory Verbal Learning Test was performed on 150 amnestic MCI and 150 normal control patients. The Chinese version of the Montreal Cognitive Assessment was measured for its test-retest reliability, sensitivity and specificity. Blood was collected for apolipoprotein E (APOE) genotyping. Compared with the control group, the amnestic MCI group performed significantly worse on all neuropsychological tests, and non-APOE-??4 carriers in the amnestic MCI group performed better than APOE-??4 carriers in the amnestic MCI group. The set of neuropsychological tests in our study could distinguish amnestic MCI participants from normal elderly participants accurately. APOE did have a role in amnestic MCI patients, but the magnitude and mechanism of its influence are not fully understood.     

Olfaction and apathy in Alzheimer's disease,mild cognitive impairment,and healthy older adults

Objectives: Apathy is a prevalent neuropsychiatric manifestation in individuals with Alzheimer's disease (AD) that is associated with decreased social functioning and increased caregiver burden. Olfactory deficits are also commonly observed in AD, and prior work has indicated a link between increased apathy and olfactory dysfunction in individuals with Parkinson's disease. Here, we examined odor identification performance in patients with probable AD (n = 172), individuals with mild cognitive impairment (MCI; n = 112), and neurologically and psychiatrically healthy older adults (n = 132) and its relation to apathy, depression, and overall psychopathology. Method: Participants were administered the Sniffin’ Sticks odor identification test and measures assessing severity of apathy, depression, and overall neuropsychiatric symptomatology. Results: Consistent with previous research, AD and MCI patients were significantly worse at identifying odors than healthy older adults. Additionally, a sex by diagnosis interaction was observed. AD patients had significantly higher levels of apathy relative to MCI and control participants. Of note, across the entire sample odor identification deficits were correlated with level of apathy at the level of p < 0.01, but not with depression or neuropsychiatric symptom severity, when controlling for Mini-Mental State Examination (MMSE) score. Conclusion: Collectively, these data suggest that olfactory disturbance and apathy in AD may result from the progression of disease pathology in shared neural substrates.     

Taste in mild cognitive impairment and Alzheimer’s disease

In this prospective study we investigated the quantitative and qualitative taste function of patients with mild cognitive impairment (MCI) and Alzheimer’s disease (AD). 29 healthy, elderly subjects, 29 MCI and 30 AD patients were tested using a validated taste test, the “taste strips”. Additionally, odor identification, odor discrimination, odor threshold, the mini-mental state examination (MMSE) and Apo E epsilon 4 status were examined. Regarding taste, there was a significant reduction of total taste scores and also the score for individual tastes on either side of the tongue between controls and MCI/AD patients. There was no significant difference in the taste scores between MCI and AD patients. A taste test may be a useful procedure for differentiating between healthy subjects and patients with MCI/AD in a clinical context. For diagnosing MCI versus AD, further tests such as smell test, MMSE, Apo E epsilon 4 status, FDG-PET and MRI appear to be useful.     

Clinical referral patterns and cognitive profile in mild cognitive impairment

BACKGROUND: There is current interest in exploring the different subtypes of mild cognitive impairment (MCI), in terms of both their epidemiology and their cognitive profile. AIMS: To examine the frequency of MCI subtypes presenting to a memory clinic and to document detailed neuropsychological profiles of patients with the amnestic subtype. METHOD: Consecutive tertiary referrals (n=187) were psychiatrically evaluated; 45 patients met criteria for amnestic mild cognitive impairment (aMCI). A subgroup of 33 patients with aMCI as well as 21 healthy controls took part in a thorough neuropsychological examination. RESULTS: Of the patients who were examined in greater neuropsychological detail, ten had pure aMCI (none with visual memory impairment only). Fifteen met criteria for non-amnestic MCI. Fifteen had normal neuropsychological profiles. Using more than one test increased sensitivity to detect episodic memory impairment. CONCLUSIONS: Amnestic MCI is an important diagnosis in secondary and tertiary memory clinics. There is scope to improve the efficacy and sensitivity of the clinical assessment of this impairment.     

Predictive accuracy of MCI subtypes for Alzheimer's disease and vascular dementia in subjects with mild cognitive impairment: a 2-year follow-up study

AIM: The aim of this study was to investigate the prognostic accuracy of different subtypes of mild cognitive impairment (MCI): amnestic MCI, multiple domain MCI, and single non-memory domain MCI, for the development of Alzheimer's dementia (AD) and vascular dementia (VaD). PATIENTS: Nondemented patients from a memory clinic cohort (n = 118), and a stroke cohort (n = 80, older than 55 years and with a cognitive impairment). RESULTS: 'Multiple domain MCI' had the highest sensitivity for both AD (80.8%) and VaD (100%), and 'amnestic MCI' had the highest specificity (85.9% for AD, 100% for VaD). The positive predictive value was low for all subtypes (0.0-32.7%), whereas the negative predictive value was high (72.8-100%). DISCUSSION: The subtype 'multiple domain MCI' has high sensitivity in identifying people at risk for developing AD or VaD. The predictive accuracy of the MCI subtypes was similar for both AD and VaD.     

Neuropsychological characteristics of mild cognitive impairment subgroups

OBJECTIVE: To describe the neuropsychological characteristics of mild cognitive impairment (MCI) subgroups identified in the Cardiovascular Health Study (CHS) cognition study. METHODS: MCI was classified as MCI-amnestic type (MCI-AT): patients with documented memory deficits but otherwise normal cognitive function; and MCI-multiple cognitive deficits type (MCI-MCDT): impairment of at least one cognitive domain (not including memory), or one abnormal test in at least two other domains, but who had not crossed the dementia threshold. The MCI subjects did not have systemic, neurological, or psychiatric disorders likely to affect cognition. RESULTS: MCI-AT (n = 10) had worse verbal and non-verbal memory performance than MCI-MCDT (n = 28) or normal controls (n = 374). By contrast, MCI-MCDT had worse language, psychomotor speed, fine motor control, and visuoconstructional function than MCI-AT or normal controls. MCI-MCDT subjects had memory deficits, though they were less pronounced than in MCI-AT. Of the MCI-MCDT cases, 22 (78.5%) had memory deficits, and 6 (21.5%) did not. MCI-MCDT with memory disorders had more language deficits than MCI-MCDT without memory disorders. By contrast, MCI-MCDT without memory deficits had more fine motor control deficits than MCI-MCDT with memory deficits. CONCLUSIONS: The most frequent form of MCI was the MCI-MCDT with memory deficits. However, the identification of memory impaired MCI groups did not reflect the true prevalence of MCI in a population, as 16% of all MCI cases and 21.5% of the MCI-MCDT cases did not have memory impairment. Study of idiopathic amnestic and non-amnestic forms of MCI is essential for an understanding of the aetiology of MCI.     

Cognitive profiles in Alzheimer's disease and in mild cognitive impairment of different etiologies

There has been increasing interest in determining whether amnestic, nonamnestic and multiple-domain subtypes of mild cognitive impairment (MCI) reflect different disease etiologies. In this study, we examined the extent to which cognitive profiles of nondemented patients with MCI diagnosed with prodromal Alzheimer's disease (AD) differed from those MCI patients diagnosed with vascular disease. We also compared these diagnostic groups to mildly demented patients diagnosed with AD and normal elderly controls. Results indicate that a majority of both MCI-AD and MCI-vascular patients experienced amnestic features and that multiple-domain was the most common presentation. MCI-AD and MCI-vascular groups did not differ on neuropsychological measures tapping memory, language, visuospatial skills/praxis or executive function. Further both MCI groups could be distinguished from dementia patients with regards to performance on measures of memory but not on non-memory measures. Considerable variability was observed in the degree of memory impairment among MCI patients with scores as much as 6 standard deviations below expected mean values. MCI-AD and MCI-vascular patients frequently exhibit both common and overlapping amnestic and nonamnestic features. The implication of these findings for future clinical research is discussed.     

CERAD test performances in amnestic mild cognitive impairment and Alzheimer's disease

OBJECTIVES: The aim of the study was to examine the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) test performances cross-sectionally in patients suffering from amnestic mild cognitive impairment (MCI) and mild Alzheimer's disease (AD). Moreover, we wanted to determine the sensitivity to amnestic MCI and mild AD, as well as the specificity of different CERAD subtests in our study groups. MATERIAL AND METHODS: Fifteen healthy elderly individuals, 15 amnestic MCI patients and 15 probable AD patients suffering from mild dementia were tested with the CERAD neurocognitive dementia screening test. RESULTS: Significant differences were found in all CERAD tests except Constructional praxis (copy) and Clock drawing between the controls and the AD group. The MCI group was differentiated from the controls only in the Wordlist learning test. In the language tests the sensitivity to MCI and AD was quite low and the specificity very high. In the savings scores the sensitivity to AD was high, but the specificity rather low. The Wordlist recognition test screened no false positives using the current cut-off score and the sensitivity to AD was 0.6, but only one MCI patient was detected using the current cut-off score. Raising the cut-off score also raised the sensitivity to MCI without dramatic loss of specificity. Cut-off scores for the Wordlist learning test and Wordlist delayed recall, which have been found to differentiate normal aging from dementia, are lacking in the Finnish CERAD. The current data indicates that the Wordlist learning test might be relatively sensitive to MCI. CONCLUSIONS: The results indicate that the Finnish CERAD test battery with its current cut-off scores has low sensitivity to MCI, and using it as a sole cognitive screening instrument for MCI and preclinical dementia might result in false negatives.