Multiple-domain aMCI Research Articles

White Matter Abnormalities in Two Different Subtypes of Amnestic Mild Cognitive Impairment.

White matter (WM) degeneration has been found during the course of cognitive decline in both Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI), however, it is unclear whether there are different WM microstructural abnormalities between two subtypes of aMCI, including single domain aMCI (aMCI-s) and multiple domain aMCI (aMCI-m). Thirty-two patients of aMCI single-domain (aMCI-s), twenty-three patients of aMCI multiple-domain (aMCI-m) and twenty-three healthy normal controls (NC) participated in this study. Neuropsychological measures and diffusion tensor imaging (DTI) data were acquired from each subject and tract-based spatial statistics (TBSS) was implemented. It was found that both aMCI groups showed significantly reduced fractional anisotropy (FA) in the right superior longitudinal fasciculus (SLF) than NC. It was also identified that, as compared to aMCI-m, aMCI-s showed significantly decreased FA in the left SLF, left uncinate fasciculus (UF) and left inferior longitudinal fasciculus (ILF), while significantly increased FA in the left anterior thalamic radiation (ATR). The correlation analysis showed that FA values in the regions with group difference were significantly correlated with cognitive functions as measured by Boston naming test and trail making test. These results suggested that the variations of aMCI may be differentiated by FA indexes and DTI may help to understand why specific signs and symptoms occur in patients.

Effects of Tai Chi on Cognition and Fall Risk in Older Adults with Mild Cognitive Impairment: A Randomized Controlled Trial.

To examine whether combined center- and home-based Tai Chi training can improve cognitive ability and reduce physiological fall risk in older adults with amnestic mild cognitive impairment (a-MCI). Randomized controlled trial. Chiang Mai, Thailand. Adults aged 60 and older who met Petersen's criteria for multiple-domain a-MCI (N = 66). Three weeks center-based and 12 weeks home-based Tai Chi (50 minutes per session, 3 times per week). Cognitive tests, including Logical Memory (LM) delayed recall, Block Design, Digit Span forward and backward, and Trail-Making Test Part B-A (TMT B-A), and fall risk index using the Physiological Profile Assessment (PPA). At the end of the trial, performance on LM, Block Design, and TMT B-A were significantly better for the Tai Chi group than the control group after adjusting for baseline test performance. The Tai Chi group also had significantly better composite PPA score and PPA parameter scores: knee extension strength, reaction time, postural sway, and lower limb proprioception. Combined center- and home-based Tai Chi training three times per week for 15 weeks significantly improved cognitive function and moderately reduced physiological fall risk in older adults with multiple-domain a-MCI. Tai Chi may be particularly beneficial to older adults with this condition.

Impairment of fine motor dexterity in mild cognitive impairment and Alzheimer's disease dementia: association with activities of daily living.

Objective:Cognitive impairment is a hallmark of mild cognitive impairment (MCI) and Alzheimer’s disease dementia (AD). Although the cognitive profile of these patients and its association with activities of daily living (ADLs) is well documented, few studies have assessed deficits in fine motor dexterity and their association with ADL performance. The objective of this research paper is to evaluate fine motor dexterity performance among MCI and AD patients and to investigate its association with different aspects of ADLs.Methods:We assessed normal aging controls, patients with multiple- and single-domain amnestic MCI (aMCI), and patients with mild AD. Fine motor dexterity was measured with the Nine-Hole Peg Test and cognitive functioning by the Mattis Dementia Rating Scale. We analyzed the data using general linear models.Results:Patients with AD or multiple-domain aMCI had slower motor responses when compared to controls. AD patients were slower than those with single-domain aMCI. We found associations between cognition and instrumental ADLs, and between fine motor dexterity and self-care ADLs.Conclusion:We observed progressive slowing of fine motor dexterity along the normal aging-MCI-AD spectrum, which was associated with autonomy in self-care ADLs.

The effects of healthy aging, amnestic mild cognitive impairment, and Alzheimer's disease on recollection and familiarity: a meta-analytic review.

It is well established that healthy aging, amnestic Mild Cognitive Impairment (aMCI), and Alzheimer's Disease (AD) are associated with substantial declines in episodic memory. However, there is still debate as to how two forms of episodic memory - recollection and familiarity - are affected by healthy and pathological aging. To address this issue we conducted a meta-analytic review of the effect sizes reported in studies using remember/know (RK), receiver operating characteristic (ROC) and process dissociation (PD) methods to examine recollection and familiarity in healthy aging (25 published reports), aMCI (9 published reports), and AD (5 published reports). The results from the meta-analysis revealed that healthy aging is associated with moderate-to-large recollection impairments. Familiarity was not impaired in studies using ROC or PD methods but was impaired in studies that used the RK procedure. aMCI was associated with large decreases in recollection whereas familiarity only tended to show a decrease in studies with a patient sample comprised of both single-domain and multiple-domain aMCI patients. Lastly, AD was associated with large decreases in both recollection and familiarity. The results are consistent with neuroimaging evidence suggesting that the hippocampus is critical for recollection whereas familiarity is dependent on the integrity of the surrounding perirhinal cortex. Moreover, the results highlight the relevance of method selection when examining aging, and suggest that familiarity deficits might be a useful behavioral marker for identifying individuals that will develop dementia.

Longitudinal Effects of Metabolic Syndrome on Alzheimer and Vascular Related Brain Pathology

Background/Aims: This study examines the longitudinal effect of metabolic syndrome (MetS) on brain-aging indices among cognitively normal (CN) and amnestic mild cognitive impairment (aMCI) groups [single-domain aMCI (saMCI) and multiple-domain aMCI (maMCI)]. Methods: The study population included 739 participants (CN = 226, saMCI = 275, and maMCI = 238) from the Alzheimer's Disease Neuroimaging Initiative, a clinic-based, multi-center prospective cohort. Confirmatory factor analysis was employed to determine a MetS latent composite score using baseline data of vascular risk factors. We examined the changes of two Alzheimer's disease (AD) biomarkers, namely [¹⁸F]fluorodeoxyglucose (FDG)-positron emission tomography (PET) regions of interest and medial temporal lobe volume over 5 years. A cerebrovascular aging index, cerebral white matter (cWM) volume, was examined as a comparison. Results: The vascular risk was similar in all groups. Applying generalized estimating equation modeling, all brain-aging indices declined significantly over time. Higher MetS scores were associated with a faster decline of cWM in the CN and maMCI groups but with a slower decrement of regional glucose metabolism in FDG-PET in the saMCI and maMCI groups. Conclusion: At the very early stage of cognitive decline, the vascular burden such as MetS may be in parallel with or independent of AD pathology in contributing to cognitive impairment in terms of accelerating the disclosure of AD pathology.

The Sub-Classification of Amnestic Mild Cognitive Impairment Using MRI-Based Cortical Thickness Measures.

Background: Amnestic mild cognitive impairment (aMCI) is considered to be the transitional stage between healthy aging and Alzheimer’s disease (AD). Moreover, aMCI individuals with additional impairment in one or more non-memory cognitive domains are at higher risk of conversion to AD. Hence accurate identification of the sub-types of aMCI would enable earlier detection of individuals progressing to AD.Methods: We examine the group differences in cortical thickness between single-domain and multiple-domain sub-types of aMCI, and as well as with respect to age-matched controls in a well-balanced cohort from the Sydney Memory and Aging Study. In addition, the diagnostic value of cortical thickness in the sub-classification of aMCI as well as from normal controls using support vector machine (SVM) classifier is evaluated, using a novel cross-validation technique that can handle class-imbalance.Results: This study revealed an increased, as well as a wider spread, of cortical thinning in multiple-domain aMCI compared to single-domain aMCI. The best performances of the classifier for the pairs (1) single-domain aMCI and normal controls, (2) multiple-domain aMCI and normal controls, and (3) single and multiple-domain aMCI were AUC = 0.52, 0.66, and 0.54, respectively. The accuracy of the classifier for the three pairs was just over 50% exhibiting low specificity (44–60%) and similar sensitivity (53–68%).Conclusion: Analysis of group differences added evidence to the hypothesis that multiple-domain aMCI is a later stage of AD compared to single-domain aMCI. The classification results show that discrimination among single, multiple-domain sub-types of aMCI and normal controls is limited using baseline cortical thickness measures.

Visual memory profiling with CANTAB in mild cognitive impairment (MCI) subtypes

Although visual memory has been shown to be impaired in amnestic mild cognitive impairment (aMCI), the differences between MCI subtypes are not well defined. The current study attempted to investigate visual memory profiles in different MCI subtypes. One hundred and seventy volunteers aged older than 50 years performed several visual memory tests included in the CANTAB battery. Participants were classified into four groups: (1) multiple domain aMCI (mda-MCI) (32 subjects); (2) single domain aMCI (sda-MCI)(57 subjects); (3) multiple domain non amnestic MCI (mdna-MCI) (32 subjects); and (4) controls (54 healthy individuals without cognitive impairment). Parametric and non parametric analyses were performed to compare the groups and to obtain their corresponding memory profiles. The mda-MCI group exhibited impairments in both dimensions of episodic memory (recognition and recollection/recall), and also in learning and working memory, whereas the sda-MCI only showed impairment in recollection-delayed recall and learning. The mdna-MCI group displayed impairment in working memory but good preservation of learning and episodic memory. The CANTAB visual memory profiles may contribute to better cognitive characterization of patients with different MCI subtypes, allowing comparison across several processes involved in visual memory such as attention, recognition, recollection and working memory.

Enhancing Diagnostic Accuracy of aMCI in the Elderly: Combination of Olfactory Test, Pupillary Response Test, BDNF Plasma Level, and APOE Genotype

Background. Amnestic Mild Cognitive Impairment (aMCI) often progresses to Alzheimer's disease. There are clinical markers and biomarkers to identify the degenerative process in the brain. Objectives. To obtain the diagnostic values of olfactory test, pupillary response to tropicamide 0.01%, BDNF plasma level, and APOE ε4 in diagnosing aMCI. Methods. Cross-sectional, comparative analysis. Results. There were 109 subjects enrolled (aMCI: 51, normal cognition: 58) with age 64 ± 5.54 years. For diagnosing aMCI, cut-off point for the olfactory score was <7 out of 10 and >22% for pupil dilatation response. Low BDNF plasma level was related significantly with olfactory deficits and aMCI (P < 0.05). Four of five subjects with homozygote e4 presented with multiple-domain aMCI. This group displayed the lowest means of olfactory score and the highest means of pupillary hypersensitivity response (P < 0.0001). Combination of olfactory deficit and pupillary hypersensitivity response in detection of aMCI was beneficial with Sp 91% and PPV 87%. In conjunction with clinical markers, BDNF plasma level and presence of APOE e4+ improved Sp and PPV. Conclusions. Combination of olfactory test and pupillary response test was useful as diagnostic tool in aMCI. In conjunction with clinical markers, low level of BDNF plasma and presence of APOE e4 improved the diagnostic value.

Different Patterns of White Matter Disruption among Amnestic Mild Cognitive Impairment Subtypes: Relationship with Neuropsychological Performance

Amnestic mild cognitive impairment (aMCI) is recognized as the prodromal phase of Alzheimer's disease (AD). Evidence showed that patients with multiple-domain (MD) aMCI were at higher risk of converting to dementia and exhibited more severe gray matter atrophy than single-domain (SD) aMCI. The investigation of the microstructural abnormalities of white matter (WM) among different subtypes of aMCI and their relations with cognitive performances can help to understand the variations among aMCI subtypes and to construct potential imaging based biomarkers to monitor the progression of aMCI. Diffusion-weighted MRI data were acquired from 40 patients with aMCI (aMCI-SD: n = 19; aMCI-MD: n = 21) and 37 healthy controls (HC). Voxel-wise and atlas-based analyses of whole-brain WM were performed among three groups. The correlations between the altered diffusion metrics of the WM tracts and the neuropsychological scores in each subtype of aMCI were assessed. The aMCI-MD patients showed disrupted integrity in multiple WM tracts across the whole-brain when compared with HCs or with aMCI-SD. In contrast, only few WM regions with diffusion changes were found in aMCI-SD as compared to HCs and with less significance. For neuropsychological correlations, only aMCI-MD patients exhibited significant associations between disrupted WM connectivity (in the body of the corpus callosum and the right anterior internal capsules) and cognitive impairments (MMSE and Digit Symb-Coding scores), whereas no such correlations were found in aMCI-SD. These findings indicate that the degeneration extensively exists in WM tracts in aMCI-MD that precedes the development of AD, whereas underlying WM pathology in aMCI-SD is imperceptible. The results are consistent with the view that aMCI is not a uniform disease entity and presents heterogeneity in the clinical progression.

Association of diabetes with amnestic and nonamnestic mild cognitive impairment

BackgroundType 2 diabetes may increase the risk of amnestic mild cognitive impairment (aMCI) through Alzheimer's disease (AD)-related and vascular pathology and may also increase the risk of nonamnestic MCI (naMCI) through vascular disease mechanisms. We examined the association of type 2 diabetes with mild cognitive impairment (MCI) and MCI subtype (aMCI and naMCI) overall and by sex. MethodsParticipants were Olmsted County, Minnesota residents (70 years and older) enrolled in a prospective, population-based study. At baseline and every 15 months thereafter, participants were evaluated using the Clinical Dementia Rating scale, a neurological evaluation, and neuropsychological testing for a diagnosis of normal cognition, MCI, and dementia by a consensus panel. Type 2 diabetes was ascertained from the medical records of participants at baseline. ResultsOver a median 4.0 years of follow-up, 348 of 1450 subjects developed MCI. Type 2 diabetes was associated (hazard ratio [95% confidence interval]) with MCI (1.39 [1.08–1.79]), aMCI (1.58 [1.17–2.15]; multiple domain: 1.58 [1.01–2.47]; single domain: 1.49 [1.09–2.05]), and the hazard ratio for naMCI was elevated (1.37 [0.84–2.24]). Diabetes was strongly associated with multiple-domain aMCI in men (2.42 [1.31–4.48]) and an elevated risk of multiple domain naMCI in men (2.11 [0.70–6.33]), and with single domain naMCI in women (2.32 [1.04–5.20]). ConclusionsDiabetes was associated with an increased risk of MCI in elderly persons. The association of diabetes with MCI may vary with subtype, number of domains, and sex. Prevention and control of diabetes may reduce the risk of MCI and Alzheimer's disease.

Recognition of facial emotional expression in amnestic mild cognitive impairment.

We examined whether recognition of facial emotional expression would be affected in amnestic mild cognitive impairment (aMCI). A total of 50 elderly persons met the initial inclusion criteria; 10 were subsequently excluded (Geriatric Depression Score > 5). 22 subjects were classified with aMCI based on published criteria (single domain aMCI [SD-aMCI], n = 10; multiple domain aMCI [MD-aMCI], n = 12); 18 subjects were cognitively normal. All underwent standard neurological and neuropsychological evaluations as well as tests of facial emotion recognition (FER) and famous faces identification (FFI). Among normal controls, FFI was negatively correlated with Mini-Mental Status Examination scores and positively correlated with executive function. Among patients with aMCI, FER was correlated with attention/speed of processing. No other correlations were significant. In a multinomial logistic regression model adjusted for age, gender, and education, a poorer score on FER, but not on FFI, was associated with greater odds of being classified as MD-aMCI (odds ratio [OR], 3.82; 95% confidence interval [CI], 1.05-13.91; p = 0.042). This association was not explained by memory or global cognitive score. There was no association between FER or FFI and SD-aMCI (OR, 1.13; 95% CI, 0.36-3.57; p = 0.836). Therefore, FER, but not FFI, may be impaired in MD-aMCI. This implies that in MD-aMCI, the tasks of FER and FFI may involve segregated neurocognitive networks.

The Effect of Bilingualism on Amnestic Mild Cognitive Impairment

Previous reports have found that lifelong bilingualism is associated with a delay in the onset of dementia, including Dementia of the Alzheimer's Type (DAT). Because amnestic mild cognitive impairment (aMCI) is often a transition stage between normal aging and DAT, our aim in this paper was to establish whether this delay in symptom onset for bilinguals would also be seen in the onset of symptoms of aMCI and whether this delay would be consistent in different subtypes of aMCI. We examined the effect of bilingualism on the age of diagnosis in individuals with single- or multiple-domain aMCI who were administered a battery of neuropsychological tests and questionnaires about their language and social background. Our results showed an interaction between aMCI type and language history. Only individuals diagnosed with single-domain aMCI demonstrated a later age of diagnosis for bilinguals (M = 79.4 years) than monolinguals (M = 74.9 years). This preliminary evidence suggests that the early protective advantage of bilingualism may be specific to single-domain aMCI, which is the type of aMCI most specifically associated with progression to DAT.

Functional Disability Profiles in Amnestic Mild Cognitive Impairment

Background/Aims: Instrumental activities of daily living (IADL) can be impaired in mild cognitive impairment (MCI), and the severity of functional disability predicts Alzheimer’s disease (AD) in amnestic MCI (aMCI). This study investigated the functional profiles of aMCI in a Chinese population. Methods: The Disability Assessment for Dementia scores of 56 subjects with single-domain aMCI (sd-aMCI) and 94 with multiple-domain aMCI (md-aMCI) were compared with normal controls (n = 64) and mild AD patients (n = 102). Results: Both the sd-aMCI (2.5 ± 2.5) and md-aMCI (3.7 ± 3.5) groups had more impaired IADL items than the controls (0.7 ± 1.7). Their IADL scores were intermediate, between the control and AD groups. sd-aMCI subjects presented deficits in 7 IADL items involving the ‘meal preparation’, ‘telephoning’, ‘finance’, ‘medications’, ‘housework’, and ‘leisure’ subscales. md-aMCI subjects presented deficits in 14 IADL items involving all subscales of daily activities. The Mini-Mental State Examination and Modified Trail-Making Test Part B scores were the major neuropsychological correlates of IADL performance in aMCI. Conclusion: IADL can be impaired in both sd-aMCI and md-aMCI. Including the functional ability assessment in the evaluation of aMCI may help clinicians to provide appropriate suggestions to maintain daily functioning.

Single- and Multiple-Domain Amnestic Mild Cognitive Impairment: Two Sides of the Same Coin

Background: Amnestic mild cognitive impairment (aMCI) is considered a transition stage between normal aging and Alzheimer’s disease (AD). Two main clinical subtypes of aMCI have been identified: (1) single-domain aMCI (aMCI-SD), with isolated episodic memory impairments, and (2) multiple-domain aMCI (aMCI-MD), with episodic memory impairments and deficits in one or more other cognitive domains. Aims: To map the pattern of gray matter (GM) atrophy associated with aMCI-SD, aMCI-MD and mild AD. Methods: A group of aMCI-SD, aMCI-MD characterized by executive function disorders, mild AD and cognitively unimpaired subjects underwent a comprehensive neuropsychological assessment and a high-definition MR brain scan. Voxel-based morphometry analysis was used to characterize the GM tissue loss in each patient group, and the common pattern of GM atrophy in aMCI-SD and aMCI-MD. Results: aMCI-SD and aMCI-MD are characterized by a common pattern of GM atrophy within the medial temporal cortex, predisposing to AD and correlating with the severity of verbal memory symptoms. Moreover, the pattern of GM atrophy observed in aMCI-SD, aMCI-MD and mild AD revealed that, from an anatomical point of view, these three clinical syndromes could represent three severity points along the continuum between normal aging and AD.

Hippocampal Volumes, Proton Magnetic Resonance Spectroscopy Metabolites, and Cerebrovascular Disease in Mild Cognitive Impairment Subtypes

Although a majority of patients with amnestic mild cognitive impairment (aMCI) progress to Alzheimer disease, the natural history of nonamnestic MCI (naMCI) is less clear. Noninvasive imaging surrogates for underlying pathological findings in MCI would be clinically useful for identifying patients who may benefit from disease-specific treatments at the prodromal stage of dementia. To determine the characteristic magnetic resonance imaging (MRI) and proton MR spectroscopy (1H MRS) profiles of MCI subtypes. Case-control study. Community-based sample at a tertiary referral center. Ninety-one patients with single-domain aMCI, 32 patients with multiple-domain aMCI, 20 patients with single- or multiple-domain naMCI, and 100 cognitively normal elderly subjects frequency-matched by age and sex. Posterior cingulate gyrus 1H MRS metabolite ratios, hippocampal volumes, and cerebrovascular disease on MRI. Patients with single-domain aMCI were characterized by small hippocampal volumes and elevated ratios of myo-inositol to creatine levels. Patients with naMCI on average had normal hippocampal volumes and 1H MRS metabolite ratios, but a greater proportion (3 of 20 patients [15%]) had cortical infarctions compared with patients with single-domain aMCI (6 of 91 [7%]). For characterization of MCI subtypes, 1H MRS and structural MRI findings were complementary. The MRI and 1H MRS findings in single-domain aMCI are consistent with a pattern similar to that of Alzheimer disease. Absence of this pattern on average in patients with naMCI suggests that cerebrovascular disease and other neurodegenerative diseases may be contributing to the cognitive impairment in many individuals with naMCI.

Predicting Rapid Clinical Progression in Amnestic Mild Cognitive Impairment

Background/Aims: We investigated whether an initial neuropsychological assessment could predict rapid progression over 12 months, from amnestic mild cognitive impairment (aMCI) to Alzheimer’s disease (AD). Methods: A longitudinal study compared the neuropsychological profiles of 27 normal controls and 18 aMCI patients at baseline and 12 months. Results: At 12 months, 24 control subjects followed up remained cognitively normal. 7 aMCI patients (6 multiple-domain aMCI and 1 single-domain aMCI) progressed to AD, and 11 were non-progressors. Prognosis was best captured by a combination of associative learning, the paired associate learning task (PAL), and global cognition, the Addenbrooke’s Cognitive Examination (ACE). Conclusion: The PAL and ACE can sensitively detect meaningful differences in scores at baseline and may be used as prognostic indicators. Multiple-domain aMCI patients progressed rapidly to AD and may be more usefully labelled as early stage AD.

Mortality in amnestic mild cognitive impairment

To assess the hazard of death in persons with and without amnestic mild cognitive impairment (aMCI). From 1987 through 2003, persons with aMCI (n = 243) and an age- and gender-matched reference group of cognitively normal persons in Olmsted County, MN, were recruited through the Mayo Clinic Alzheimer's Disease Patient Registry and followed prospectively through 2004. Survival was estimated using Kaplan-Meier survival curves, and the hazard of death for the aMCI cohort vs the reference cohort was estimated using Cox proportional hazards models. Over a median follow-up of 5.7 years, persons with aMCI had increased mortality (hazard ratio [HR] = 1.7; 95% CI: 1.3 to 2.3) vs reference subjects. The hazard of death by aMCI subtype was 1.5 in persons with single-domain aMCI (95% CI: 1.1 to 2.1) and 2.9 in persons with multiple-domain aMCI (95% CI: 1.9 to 4.6) vs reference subjects. Analyses restricted to aMCI cases showed an interaction between aMCI subtype and APOE-epsilon4 allele status (p = 0.003). Among aMCI cases with an APOE-epsilon4 allele, there was no difference in mortality between single- and multiple-domain aMCI (HR = 1.2; 95% CI: 0.6 to 2.3). However, among aMCI cases with no APOE-epsilon4 allele, the hazard of death in multiple-domain aMCI was 4.6 (95% CI: 2.3 to 9.1) vs single-domain aMCI. Amnestic mild cognitive impairment is associated with increased mortality, which is greater in multiple-domain aMCI than in single-domain aMCI. Mortality in aMCI subtypes may vary by APOE-epsilon4 allele status.