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An exploration of subgroups of mild cognitive impairment based on cognitive, neuropsychiatric and functional features: analysis of data from the National Alzheimer's Coordinating Center.

ABSTRACT: To empirically expand the existing subtypes of mild cognitive impairment (MCI) by incorporating information on neuropsychiatric and functional features, and to assess whether cerebrovascular disease (CVD) risk factors are associated with any of these subgroups.Latent class analysis using 1,655 patients with MCI.Participants in the Uniform Data Set (UDS) from 29 National Institutes of Health-supported Alzheimer's Disease Centers.Patients with a consensus diagnosis of MCI from each center and with a Mini-Mental State Examination score of 22 or greater.UDS cognitive battery, Neuropsychiatric Inventory Questionnaire, and Functional Assessment Questionnaire administered at initial visit.Seven empirically based subgroups of MCI were identified: 1) minimally impaired (relative frequency, 12%); 2) amnestic only (16%); 3) amnestic with functional and neuropsychiatric features (16%); 4) amnestic multidomain (12%); 5) amnestic multidomain with functional and neuropsychiatric features (12%); 6) functional and neuropsychiatric features (15%); and 7) executive function and language impairments (18%). Two of these subgroups with functional and neuropsychiatric features were at least 3.8 times more likely than the minimally impaired subgroup to have a Rosen-Hachinski score of 4 or greater, an indicator of probable CVD.Findings suggest that there are several distinct phenotypes of MCI characterized by prominent cognitive features, prominent functional features, and neuropsychiatric features or a combination of all three. Subgroups with functional and neuropsychiatric features are significantly more likely to have CVD, which suggests that there may be distinct differences in disease etiology from the other phenotypes.

SUBMITTER: Hanfelt JJ

PROVIDER: S-EPMC3202691 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature

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An exploration of subgroups of mild cognitive impairment based on cognitive, neuropsychiatric and functional features: analysis of data from the National Alzheimer's Coordinating Center.

Hanfelt John J JJ Wuu Joanne J Sollinger Ann B AB Greenaway Melanie C MC Lah James J JJ Levey Allan I AI Goldstein Felicia C FC

The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry 20111101 11

<h4>Objectives</h4>To empirically expand the existing subtypes of mild cognitive impairment (MCI) by incorporating information on neuropsychiatric and functional features, and to assess whether cerebrovascular disease (CVD) risk factors are associated with any of these subgroups.<h4>Design</h4>Latent class analysis using 1,655 patients with MCI.<h4>Setting</h4>Participants in the Uniform Data Set (UDS) from 29 National Institutes of Health-supported Alzheimer's Disease Centers.<h4>Participants</ ...[more]

PMID: 22024618

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Project description:BackgroundNeuropsychiatric symptoms (NPSs) are common in Alzheimer's disease (AD). NPSs contribute to patients' distress, caregiver burden, and institutionalization. White matter hyperintensities (WMHs) appear on magnetic resonance imaging, usually indicative of cerebrovascular disease. WMHs have been associated with certain NPSs. We aimed to assess the relationship between WMH and NPS severity in mild cognitive impairment (MCI) due to AD (MCI-AD) and in AD and to assess the ability of WMHs to predict NPS progression. Data were obtained from the National Alzheimer's Coordinating Center.MethodsA total of 252 participants (114 with MCI-AD and 138 with AD) were used in this study. Baseline WMHs were quantified using an automated segmentation technique. NPSs were measured using the Neuropsychiatric Inventory. Mixed-effect models and correlations were used to determine the relationship between WMHs and NPSs.ResultsLongitudinal mixed-effect models revealed a significant relationship between increase in Neuropsychiatric Inventory total scores and baseline WMHs (p = .014). There was a significant relationship between baseline WMHs and an increase in delusions (p = .023), hallucinations (p = .040), agitation (p = .093), depression (p = .017), and irritability (p = .002). Correlation plot analysis showed that baseline whole-brain WMHs predicted change in future Neuropsychiatric Inventory total scores (r = .169, p = .008) and predicted change in future agitation severity scores (r = .165, p = .009). WMHs in the temporal lobes (r = .169, p = .008) and frontal lobes (r = .153, p = .016) contributed most to this change.ConclusionsDepression, irritability, and agitation are common NPSs and very distressful to patients and caregivers. Our findings of increased NPS severity over time in MCI-AD and AD with increased WMHs have important implications for treatment, arguing for aggressive treatment of vascular risk factors in patients with MCI-AD or AD.

Project description:BACKGROUND:Longitudinal investigations are needed to improve understanding of the contributions of cerebral small vessel disease to the clinical manifestation of Alzheimer's disease, particularly in the early disease stages. This study leveraged the National Alzheimer's Coordinating Center Uniform Data Set to longitudinally examine the association between white matter hyperintensities and neuropsychological, neuropsychiatric, and functional decline among participants with normal cognition. METHODS:The sample included 465 participants from the National Alzheimer's Coordinating Center Uniform Data Set who had quantitated volume of white matter hyperintensities from fluid-attenuated inversion recovery MRI, had normal cognition at the time of their MRI, and were administered the National Alzheimer's Coordinating Center Uniform Data Set neuropsychological test battery within 1?year of study evaluation and had at least two post-MRI time points of clinical data. Neuropsychiatric status was assessed by the Geriatric Depression Scale-15 and Neuropsychiatric Inventory-Questionnaire. Clinical Dementia Rating Sum of Boxes defined functional status. For participants subsequently diagnosed with mild cognitive impairment (MCI) or dementia, their impairment must have been attributed to Alzheimer's disease (AD) to evaluate the relationships between WMH and the clinical presentation of AD. RESULTS:Of the 465 participants, 56 converted to MCI or AD dementia (average follow-up?=?5?years). Among the 465 participants, generalized estimating equations controlling for age, sex, race, education, APOE ?4, and total brain and hippocampal volume showed that higher baseline log-white matter hyperintensities predicted accelerated decline on the following neuropsychological tests in rank order of effect size: Trails B (p?<?0.01), Digit Symbol Coding (p?<?0.01), Logical Memory Immediate Recall (p?=?0.02), Trail Making A (p?<?0.01), and Semantic Fluency (p?<?0.01). White matter hyperintensities predicted increases in Clinical Dementia Rating Sum of Boxes (p?<?0.01) and Geriatric Depression Scale-15 scores (p?=?0.01). Effect sizes were comparable to total brain and hippocampal volume. White matter hyperintensities did not predict diagnostic conversion. All effects also remained after including individuals with non-AD suspected etiologies for those who converted to MCI or dementia. CONCLUSIONS:In this baseline cognitively normal sample, greater white matter hyperintensities were associated with accelerated cognitive, neuropsychiatric, and functional decline independent of traditional risk factors and MRI biomarkers for Alzheimer's disease.

Dataset Information

An exploration of subgroups of mild cognitive impairment based on cognitive, neuropsychiatric and functional features: analysis of data from the National Alzheimer's Coordinating Center.

Publications

An exploration of subgroups of mild cognitive impairment based on cognitive, neuropsychiatric and functional features: analysis of data from the National Alzheimer's Coordinating Center.

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