Amnestic Mild Cognitive Impairment Group Research Articles

FMRI Activation Changes during Successful Episodic Memory Encoding and Recognition in Amnestic Mild Cognitive Impairment Relative to Cognitively Healthy Older Adults

Background/Aims: Previous functional MRI studies in individuals with amnestic mild cognitive impairment (AMCI), a putative, prodromal form of Alzheimer’s disease, reveal substantial regional changes in brain activation during episodic memory function. Methods: Functional MRI was applied to examine changes in brain activation during different stages of episodic memory function using a subsequent memory task in individuals with AMCI relative to older normal controls. Results: We found that the AMCI group displayed greater activation in the right hippocampus but less activation in the frontal cortex relative to the older normal control group during intentional encoding of items that were subsequently recognized. We observed nearly the opposite pattern of results for successful recognition. The AMCI group displayed less activation in the medial temporal cortex but greater activation in the frontal cortex. In addition, the AMCI group showed reduced activation in the medial temporal and frontal cortices during incidental encoding of novel information during recognition. Conclusion: The results of the present study suggest that brain activation differences in individuals with AMCI are modulated by the stage of episodic memory examined (i.e. intentional vs. incidental encoding vs. recognition). These observations may help to clarify some of the conflicting findings regarding brain activation changes in AMCI.

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

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. An exploratory factor analysis was performed on 260 outpatient evaluations from 2002-2006. Only the seven items requiring motor responses were included. 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. 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.

Patterns of Atrophy Differ Among Specific Subtypes of Mild Cognitive Impairment

In most patients, mild cognitive impairment (MCI) represents the clinically evident prodromal phase of dementia. This is most well established in amnestic MCI, which is most commonly a precursor to Alzheimer disease (AD). It follows, however, that subjects with MCI who have impairment in nonmemory domains may progress to non-AD degenerative dementias. To investigate patterns of cerebral atrophy associated with specific subtypes of MCI. Case-control study. Community-based sample at a tertiary referral center. One hundred forty-five subjects with MCI and 145 age- and sex-matched cognitively normal control subjects. Mild cognitive impairment was classified as amnestic, single cognitive domain; amnestic, multiple domain; nonamnestic, single domain; and nonamnestic, multiple domain. Subjects with nonamnestic single-domain MCI were classified into language, attention/executive, and visuospatial subgroups on the basis of specific cognitive impairment. Patterns of gray matter loss in the MCI groups compared with control subjects, assessed using voxel-based morphometry. Subjects in the amnestic single- and multiple-domain groups showed loss in the medial and inferior temporal lobes compared with control subjects, and those in the multiple-domain group also had involvement of the posterior temporal lobe, parietal association cortex, and posterior cingulate. Subjects in the nonamnestic single-domain group with language impairment showed loss in the left anterior inferior temporal lobe. The group with attention/executive deficits showed loss in the basal forebrain and hypothalamus. No coherent patterns of loss were observed in the other subgroups. The pattern of atrophy in the amnestic MCI groups is consistent with the concept that MCI in most of these subjects represents prodromal AD. However, the varying patterns in the language and attention/executive subgroups suggest that these subjects may have a different underlying disorder.

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.

Screening for amnestic mild cognitive impairment and early Alzheimer's disease with M@T (Memory Alteration Test) in the primary care population

To design and validate a new screening test for amnestic Mild Cognitive Impairment (A-MCI) and early stage Alzheimer's disease (AD). We develop a verbal episodic and semantic memory test: the Memory Alteration Test (M@T). Discriminative validity was assessed in a population sample of 400 aged individuals from primary care population centres in Barcelona, Spain, 50 patients with A-MCI according to Petersen et al. criteria, and 66 with early AD (Global Deterioration Scale-4 stage) according to the NINCDS-ADRDA criteria. The M@T is quick, 5-min, and easy to administer and to score. M@T mean scores were significantly different between all groups: 41.4 (SD = 4.9) in the primary care population, 31.5 (SD = 3.9) in the A-MCI group and 21.8 (SD = 4.9) in early AD. A cut-off score of 37 points had a sensitivity of 96% and a specificity of 79% for A-MCI diagnosis (AUC = 0.932). A cut-off score of 28 points had a sensitivity of 92% and a specificity of 98% for early AD diagnosis (AUC = 0.99) and a sensitivity of 87 % and specificity of 82% to differentiate between A-MCI and AD patients. The M@T provides efficient and valid screening for A-MCI and early stage AD, and discriminates between A-MCI and early AD patients.

P2-173: Impairment of spatial memory in patients with mild cognitive impairment precedes development of Alzheimer’s disease

Hippocampus dependent spatial navigation is impaired early among the cognitive functions, but has been little studied in Alzheimer's disease (AD) and in Mild Cognitive Impairment (MCI). Failure in real life space orientation is common in AD patients and may be an early symptom of hippocampal damage in MCI patients. To evaluate contribution of spatial memory testing as a potential biomarker in MCI and in AD. 37 patients were recruited among clients of our Memory Disorders Clinic and subsequently classified into 3 groups: probable AD (n=20), amnestic MCI (n=8), subjective memory complaints not fulfilling MCI criteria (SMC)(n=9). Results were referred to age and sex matched control group (n=15). Diagnosis of AD dementia was based on DSM IV and NINCDS– ADRDA criteria. Petersen's criteria for MCI were applied. MRI, MMSE and extensive neuropsychological testing were done in all subjects. Spatial memory was tested in an enclosed arena 2.9m in diameter with orientation cues on the wall and in a P.C. version with a map view of the arena projected on a monitor. The test called the Hidden Goal Task (HGT) was used—the subjects should locate a hidden goal inside of the arena in 4 subtests. Depending on the subtest, the subjects used the start position and/or cues on the wall for navigation to focus on either allocentric or egocentric navigation. The searching trajectory was recorded by an overhead camera and a P.C. tracking system. A significantly worse performance in AD group compared to controls (p <0.01) was proved; amnestic MCI group was significantly impaired in subtests focused on egocentric (p <0.05) and allocentric (p <0.01) orientation compared to controls, but less than in AD (p <0.05). SMC group wasn't significantly impaired in any of the subtests compared to controls. MMSE test correlated with HGT results (p <0.01). Spatial memory deficit in MCI patients is less profound than among AD patients, but it is qualitatively similar. Spatial memory testing can be profitable for the assessment of real life disability, longitudinal monitoring and prognosis of AD development in patients with amnestic MCI.

The functional anatomy of divided attention in amnestic mild cognitive impairment

Recent neuroimaging studies have demonstrated changes in brain function in cognitively normal subjects at increased risk of developing Alzheimer's disease. Amnestic mild cognitive impairment (AMCI) carries a high risk of developing into Alzheimer's disease. In AMCI altered cortical activation has been demonstrated during memory tasks, using functional MRI (fMRI). Memory and attention are closely related cognitive functions. It is unclear whether the memory impairment of AMCI is associated with attentional deficits of the sort likely to be revealed by tasks requiring divided attention. Ten older adults (mean age 72 years, range 57-81 years) with AMCI were compared with healthy matched controls on divided attention and passive sensory processing tasks using fMRI. During the divided attention task both groups activated similar regions of left hemispheric prefrontal and extrastriate visual cortex. However, the AMCI group had attenuated prefrontal activation compared with age matched controls. On the passive sensory processing task there was no difference between the AMCI and control groups. We conclude that there are changes in the functional network subserving divided attention in patients with AMCI as reflected in the attenuation of prefrontal cortical activation. These findings have implications for evaluating cognition in AMCI and also for monitoring the effects of future treatments in AMCI.

Quantitative and Qualitative Impairments in Semantic Fluency, but not Phonetic Fluency, as a Potential Risk Factor for Alzheimer's Disease

AbstractQualitative aspects of verbal fluency may be more useful in discerning the precise cause of any quantitative deficits in phonetic or category fluency, especially in the case of mild cognitive impairment (MCI), a possible intermediate stage between normal performance and Alzheimer's disease (AD). The aim of this study was to use both quantitative and qualitative (switches and clusters) methods to compare the phonetic and category verbal fluency performance of elderly adults with no cognitive impairment (n = 51), significant memory impairment (n = 16), and AD (n = 16). As expected, the AD group displayed impairments in all quantitative and qualitative measures of the two fluency tasks relative to their age- and education-matched peers. By contrast, the amnestic MCI group produced fewer animal names on the semantic fluency task than controls and showed normal performance on the phonetic fluency task. The MCI group's inferior category fluency performance was associated with a deficit in their category-switching rate rather than word cluster size. Overall, the results indicate that a semantic measure such as category fluency when used in conjunction with a test of episodic memory may increase the sensitivity for detecting preclinical AD. Future research using external cues and other measures of set shifting capacity may assist in clarifying the origin of the amnestic MCI-specific category-switching deficiency.

Subtle Memory Decline over 12 Months in Mild Cognitive Impairment

Objective: Screening of normal older persons for progressive memory decline is a worthwhile strategy in the pursuit of the earliest possible stages of pre-clinical Alzheimer’s disease (AD) or mild cognitive impairment (MCI). Reliable tests are needed to both detect MCI and measure the natural history of decline over months rather than years. We aimed to detect memory decline over 1 year in a group of older individuals with well-characterised amnestic MCI. Methods: The continuous learning task (CLT) from the CogState test battery was administered 8 times in 12 months to 15 individuals with MCI and 35 controls matched for age, education, IQ and gender. All subjects were recruited from an ongoing aging study. The rate of change in CLT performance over the year was compared between groups and also compared to that detected with a word list learning task and a computerised paired associate learning task. Results: At baseline, memory performance in the amnestic MCI group was significantly worse than controls on all memory tests. However, at 12 months the magnitude of the difference between the groups had increased significantly on the CLT due to decline in memory accuracy in the MCI group. No decline over 12 months was detectable on the routine memory tests. Conclusions: Subtle memory decline is detectable in amnestic MCI using reliable and sensitive tests of memory. Such measures may assist in the early identification of AD and also in trials of putative disease-modifying therapies to be conducted over as little as 12 months.