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1.  Cardiac Disease Increases Risk of Non-amnestic Mild Cognitive Impairment: Stronger impact in women 
JAMA neurology  2013;70(3):374-382.
Objective
Non-amnestic mild cognitive impairment (naMCI), a putative precursor of vascular and other non-Alzheimer’s disease dementias, is hypothesized to have a vascular etiology. We investigated the association of cardiac disease with amnestic (aMCI) and non-amnestic (naMCI) MCI.
Design
A prospective, population-based, cohort study with a median 4.0 years of follow-up.
Setting
Olmsted County, Minnesota.
Participants
Participants were evaluated at baseline and every 15 months using the Clinical Dementia Rating scale, a neurological evaluation, and neuropsychological testing. A diagnosis of normal cognition, MCI, or dementia was made by consensus. Cardiac disease at baseline was assessed from the participant’s medical records.
Main outcome measures
Incident MCI, aMCI, naMCI.
Results
Among 1,450 subjects free of MCI or dementia at baseline, 366 developed MCI. Cardiac disease was associated with an increased risk of naMCI (hazard ratio [HR] 95% confidence interval; 1.77 [1.16–2.72]). However, the association varied by sex (P for interaction = .02). Cardiac disease was associated with an increased risk of naMCI (HR, 3.07 [1.58–5.99]) in women, but not in men (HR, 1.16 [0.68–1.99]. Cardiac disease was not associated with any MCI or aMCI.
Conclusion
Cardiac disease is an independent risk factor for naMCI, within sex comparisons showed a stronger association in women. Prevention and management of cardiac disease and vascular risk factors may reduce the risk of naMCI.
doi:10.1001/jamaneurol.2013.607
PMCID: PMC3734560  PMID: 23358884
2.  What is the quality of life in the oldest old? 
International psychogeriatrics / IPA  2011;23(6):1003-1010.
Background
Maintaining and improving quality of life has become a major focus in geriatric medicine, but the oldest old have received limited attention in clinical investigations. We aimed to investigate the relationship between self-perceived and caregiver-perceived quality of life (QOL), cognitive functioning, and depressive symptoms in the oldest old.
Methods
This IRB-approved prospective study recruited community dwellers aged 90–99 years old. Collected data included neurological evaluation, DSM III-R criteria for dementia, Mini-Mental State Examination (MMSE), Dementia Rating Scale (DRS), Geriatric Depression Scale (GDS), Record of Independent Living (ROIL), and QOL assessment using the Linear Analogue Self Assessment (LASA).
Results
Data on 144 subjects (56 cognitively normal (normal), 13 mild cognitive impairment (MCI), 41 dementia (DEM), 34 dementia with stroke and parkinsonism (DEMSP)) over a three-year period were analyzed. Mean ages ranged from 93 to 94 years, and the majority were female with at least high school education. Overall functional ability was higher in groups without dementia (p < 0.0001). All subjects reported high overall QOL (range 6.76–8.3 out of 10), regardless of cognitive functioning. However, caregivers perceived the subjects’ overall QOL to be lower with increasing severity of cognitive impairment (p < 0.0001). Lower GDS scores correlate with higher self-perceived overall QOL (ρ = −0.38, p < 0.0001).
Conclusions
In our community sample of the oldest old, there was a fairly high level of overall QOL, whether or not cognitive impairment exists. Individuals perceive their QOL better than caregivers do, and the difference in subjects’ and caregivers’ perception is more pronounced for the groups with dementia. QOL is more strongly correlated with depressive symptoms than with dementia severity.
doi:10.1017/S1041610210002462
PMCID: PMC3924179  PMID: 21281556
geriatric; well being; cognition; depression; dementia; stroke; parkinsonism; MCI
3.  ApoE and Quality of Life in Nonagenarians 
Objectives
ApoE ε4 is associated with adverse health conditions that negatively impact the quality of life (QOL). The relationship between ApoE ε4 and QOL has not been explored in the oldest old. Our study aimed to examine ApoE in the oldest old, and explore its association with QOL.
Design
Cross-sectional cohort study.
Setting
A medium sized community in Olmsted County, Minnesota, USA.
Participants
90–99 year old individuals living independently or in long term care environments.
Measurements
We collected demographic information and measured cognitive function (Short Test of Mental Status [STMS], Mini-Mental State Examination [MMSE], Mattis Dementia Rating Scale [DRS]), QOL (Linear Analogue Self Assessment [LASA]) and ApoE distribution. Subjects were classified as cognitively normal, mild cognitive impairment (MCI), dementia (DEM), or dementia with stroke and/or parkinsonism (DEMSP). Regression model was used to assess the predictors of QOL.
Results
121 subjects (45 cognitively normal, 13 MCI, 34 DEM, 29 DEMSP) aged 90–99,106 (87.6 %) females, were included. Frequency of ApoE ε3 allele was highest [194 (80.2%): ε2/3 18, ε3/3 77, ε3/4 22] followed by ApoE ε4 [25 (10.3%): ε2/4 3, ε3/4 22] and ApoE ε2 [23 (9.5%; ε2/2 1, ε2/3 18, ε2/4 3]. None of the subjects carried ApoE ε4/4 genotype. QOL was similar between ApoE ε4 carrier and non-carriers. Physical well-being, emotional well-being, intellectual well-being, social connectedness and coping ability were positively associated with QOL, whereas male gender, DEMSP, pain frequency and pain severity were negatively associated.
Conclusions
The most common ApoE in the oldest old was ε3/3 genotype and ε3 allele. No association was found between ApoE ε4 and QOL. However, those with high physical, emotional and intellectual well being, social connectedness and coping ability had the highest overall QOL.
doi:10.1016/j.jamda.2012.06.012
PMCID: PMC3461124  PMID: 22863665
Well being; oldest old; apolipoprotein E
4.  Vegetables, Unsaturated Fats, Moderate Alcohol Intake, and Mild Cognitive Impairment 
Background/Aims
To investigate associations of the Mediterranean diet (MeDi) components and the MeDi score with mild cognitive impairment (MCI).
Methods
Participants (aged 70–89 years) were clinically evaluated to assess MCI and dementia, and completed a 128-item food frequency questionnaire.
Results
163 of 1,233 nondemented persons had MCI. The odds ratio of MCI was reduced for high vegetable intake [0.66 (95% CI = 0.44–0.99), p = 0.05] and for high mono-plus polyunsaturated fatty acid to saturated fatty acid ratio [0.52 (95% CI = 0.33–0.81), p = 0.007], adjusted for confounders. The risk of incident MCI or dementia was reduced in subjects with a high MeDi score [hazard ratio = 0.75 (95% CI = 0.46–1.21), p = 0.24].
Conclusion
Vegetables, unsaturated fats, and a high MeDi score may be beneficial to cognitive function.
doi:10.1159/000305099
PMCID: PMC2889256  PMID: 20502015
Mild cognitive impairment; Dietary intake; Moderate alcohol intake; Unsaturated fatty acids; Mediterranean diet; Longitudinal; Prevalence studies; Incidence studies; Population-based
5.  Association of Prior Stroke with Cognitive Function and Cognitive Impairment: A Population-based Study 
Archives of neurology  2009;66(5):614-619.
Background
Defining the nature of the contribution of stroke to cognitive impairment remains challenging.
Methods
We randomly selected Olmsted County, MN residents aged 70–89 years on October 1, 2004 and invited eligible non-demented subjects to participate. Participants (n = 2,050) were evaluated with an informant interview, a neurological evaluation, and neuropsychological testing. Neuropsychological testing included 9 tests to assess memory, attention and executive function, visuospatial cognition and language. Subjects were diagnosed by consensus as cognitively normal, MCI (either amnestic (a-) or non-amnestic (na-)), or dementia. A history of stroke was obtained from the subject and confirmed in the medical record. We computed the odds ratios (OR) for a clinical diagnosis of MCI or for scoring in the lowest quartile on each cognitive domain.
Results
There were 1640 cognitively normal and 329 MCI subjects, 241 a-MCI and 88 na-MCI. In fully adjusted models with non-demented subjects only, a history of stroke was associated with a higher odds ratio (OR) of na-MCI (OR= 2.85, 95% CI 1.61 – 5.04) than a-MCI (OR= 1.77, 95% CI 1.14 – 2.74). A history of stroke was also associated with impaired function in each cognitive domain except memory. The association was strongest for attention and executive function (OR=2.48, 95% CI 1.73 – 3.53). APOE e4 genotype was associated only with a-MCI and with impaired memory function.
Conclusions
In this population-based sample of non-demented persons, a history of stroke was particularly associated with na-MCI and with impairment in non-memory cognition. APOE e4 genotype was associated with memory impairment and a-MCI.
doi:10.1001/archneurol.2009.30
PMCID: PMC3050015  PMID: 19433661
6.  Metabolic Syndrome, Inflammation, and Non-Amnestic Mild Cognitive Impairment in Older Persons: A Population-Based Study 
The metabolic syndrome (MetS) is more strongly associated with cognitive impairment in the presence of inflammation. This suggests that the association of MetS with mild cognitive impairment (MCI) may vary with the etiology and the subtype of MCI. This study investigated the association between MetS with or without inflammation and MCI (amnestic [a-MCI] and non-amnestic [na-MCI]). We studied a randomly selected sample of 1969 subjects (ages 70 to 89 years) from Olmsted County, MN, using the Clinical Dementia Rating Scale, a neurological evaluation, and neuropsychological testing. Data for participants were reviewed for a diagnosis of normal cognition, MCI, or dementia. Clinical components of MetS were ascertained by interview and confirmed from the medical records; biochemical measurements were assayed from a blood draw. We compared 88 na-MCI cases and 241 a-MCI cases with 1640 cognitively normal subjects. MetS was not associated with either na-MCI or a-MCI. High C-reactive protein (CRP highest tertile vs lowest tertile) was associated with na-MCI (odds ratio [OR] = 1.85; 95% confidence interval [CI] = 1.05, 3.24) but not with a-MCI, after adjusting for sex, age, and years of education. The combination of MetS and high CRP (compared to no Mets and lowest CRP tertile) was associated with na-MCI (OR = 2.31; 95% CI = 1.07, 5.00), but not with a-MCI (OR = 0.96; 95% CI = 0.59, 1.54). The combined presence of MetS and high levels of inflammation is associated with na-MCI in this elderly cohort, and suggests etiologic differences in MCI subtypes.
doi:10.1097/WAD.0b013e3181a4485c
PMCID: PMC2837096  PMID: 19568151
metabolic syndrome; insulin resistance; mild cognitive impairment; C-reactive protein; inflammation; cross-sectional study
7.  COMPARATIVE DIAGNOSTIC UTILITY OF DIFFERENT MR MODALITIES IN MILD COGNITIVE IMPAIRMENT AND ALZHEIMER’S DISEASE 
This study compares diagnostic accuracy of magnetic resonance (MR)-based hippocampal volumetry, single voxel (SV) 1H MR Spectroscopy (MRS) and MR diffusion weighted imaging (DWI) measurements in discriminating patients with amnestic mild cognitive impairment (MCI), Alzheimer’s disease (AD) and normally aging elderly. Sixty-one normally aging elderly, 24 MCI, and 22 AD patients underwent MR-based hippocampal volumetry, 1H MRS, and DWI. 1H MRS voxels were placed over both of the posterior cingulate gyri and N-acetyl aspartate (NAA) / creatine (Cr), myoinositol (MI) /Cr and NAA /MI ratios were obtained. Apparent diffusion coefficient (ADC) maps were derived from DWI and hippocampal borders were traced to measure hippocampal ADC. At 80% specificity, the most sensitive single measurement to discriminate MCI (79 %) and AD (86 %) from controls was hippocampal volumes. The most sensitive single measurement to discriminate AD from MCI was posterior cingulate gyrus NAA /Cr (67 %). At high specificity (>85 –90%) combinations of MR measures had superior diagnostic sensitivity compared to any single MR measurement for the AD vs. control and control vs. MCI comparisons. The MR measures that best discriminate more from less affected individuals along the cognitive continuum from normal to AD vary with disease severity. Selection of imaging measures used for clinical assessment or monitoring efficiency of therapeutic intervention should be tailored to the clinical stage of the disease.
PMCID: PMC2796574  PMID: 12411762
Alzheimer’s disease; mild cognitive impairment; 1H MRS; diffusion weighted imaging; hippocampal volumetry; MRI
8.  Age, family history, and memory and future risk for cognitive impairment 
Purpose
To provide a clinical tool for calculating a patient's future risk for developing cognitive impairment based on age, family history, and AVLT retention.
Participants
1019 cognitively normal persons followed for an average of 5 years. 159 participants were eventually diagnosed with cognitive impairment.
Results
Risk of developing cognitive impairment increases with age and family history, but decreases with better memory performance. A nomogram is provided for calculation of relative risk of developing cognitive impairment in combinations of age, family history, and memory performance.
Conclusions
These results enhance clinicians' ability to provide information to a patient about risk of cognitive impairment.
doi:10.1080/13803390802020443
PMCID: PMC2750804  PMID: 18608678
cognitive decline; dementia; risk; AVLT; family history
9.  The Mayo Clinic Study of Aging: Design and Sampling, Participation, Baseline Measures and Sample Characteristics 
Neuroepidemiology  2008;30(1):58-69.
Background
The objective of this study was to establish a prospective population-based cohort to investigate the prevalence, incidence and risk factors for mild cognitive impairment (MCI) and dementia.
Methods
The Olmsted County, Minn., population, aged 70–89 years on October 1, 2004, was enumerated using the Rochester Epidemiology Project. Eligible subjects were randomly selected and invited to participate. Participants underwent a comprehensive in-person evaluation including the Clinical Dementia Rating Scale, a neurological evaluation and neuropsychological testing. A consensus diagnosis of normal cognition, MCI or dementia was made by a panel using previously published criteria. A subsample of subjects was studied via telephone interview.
Results
Four hundred and two subjects with dementia were identified from a detailed review of their medical records but were not contacted. At baseline, we successfully evaluated 703 women aged 70–79 years, 769 women aged 80–89 years, 730 men aged 70–79 years and 517 men aged 80–89 years (total n = 2,719). Among the participants, 2,050 subjects were evaluated in person and 669 via telephone.
Conclusions
Strengths of the study are that the subjects were randomly selected from a defined population, the majority of the subjects were examined in person, and MCI was defined using published criteria. Here, we report the design and sampling, participation, baseline measures and sample characteristics.
doi:10.1159/000115751
PMCID: PMC2821441  PMID: 18259084
Cognitive impairment; Prevalence; Incidence; Risk factors; Cohort studies; Data collection instruments

Results 1-9 (9)