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1.  MRI Volume of the Angular Gyri Predicts Financial Skill Deficits in Patients with Amnestic Mild Cognitive Impairment 
OBJECTIVES
Persons with amnestic mild cognitive impairment (MCI) have demonstrated subtle impairments in IADLs including financial abilities, although the underlying brain changes related to these IADL impairments is poorly understood. The purpose of this investigation was to better understand how brain atrophy in MCI as measured by MRI volumetrics could impact IADLs such as financial abilities.
DESIGN
Controlled, matched sample, cross-sectional analysis regressing MRI volumetrics with financial performance measures.
SETTING
University medical and research center.
PARTICIPANTS
Thirty-eight MCI patients and 28 older adult controls.
MEASUREMENTS
MRI volumetric measurement of the hippocampi, angular gyri, precunei, and medial frontal lobes. Participants also completed neuropsychological tests and the Financial Capacity Instrument (FCI).
RESULTS
We performed correlations between FCI scores and MRI volumes in the MCI group. Patients with MCI performed significantly below controls on the FCI and had significantly smaller hippocampi. Among MCI patients, performance on the FCI was moderately correlated with angular gyri and precunei volumes. Regression models demonstrated that angular gyri volumes were predictive of FCI scores. Tests of mediation showed that the relationship of angular gyri volume with FCI score was partially mediated by measures of arithmetic and possibly attention.
CONCLUSION
Impaired financial abilities in amnestic MCI correspond with volume of the angular gyri as mediated by arithmetic knowledge. The findings suggest that early neuropathology within the lateral parietal region in MCI leads to a breakdown of cognitive abilities that impact everyday financial skills. The findings have implications for diagnosis and clinical care of patients with MCI and AD.
doi:10.1111/j.1532-5415.2009.02679.x
PMCID: PMC3711192  PMID: 20374402
magnetic resonance imaging; mild cognitive impairment; financial capacity; angular gyrus; hippocampus; precuneus
2.  White Matter Abnormalities and Cognition in a Community Sample 
White matter hyperintensities (WMH) can compromise cognition in older adults, but differences in sampling, WMH measurements, and cognitive assessments contribute to discrepant findings across studies. We examined linear and nonlinear effects of WMH volumes on cognition in 253 reasonably healthy adults. After adjusting for demographic characteristics and total brain volumes, WMH burden was not associated with cognition in those aged 20–59. In participants aged 60 and older, models accounted for ≥58% of the variance in performance on tests of working memory, processing speed, fluency, and fluid intelligence, and WMH volumes accounted for variance beyond that explained by age and other demographic characteristics. Larger increases in WMH burden over 5 years also were associated with steeper cognitive declines over the same interval. Results point to both age-related and age-independent effects of WMH on cognition in later life and suggest that the accumulation of WMH might partially explain normal age-related declines in cognition.
doi:10.1093/arclin/acp037
PMCID: PMC2765350  PMID: 19617597
White matter hyperintensities; Aging; Cognition; Cardiovascular disease
3.  Racial and Sex Differences in Associations between Activities of Daily Living and Cognition Among Community-Dwelling Older Adults 
Background/Objectives
Appropriate management of older adults includes assessment of cognition and understanding its relationship to function. The aim of this analysis was to examine the association between function measured by activities of daily living, both basic (BADL) and instrumental (IADL), and cognition assessed by MMSE scores among older African American and non-Hispanic White community-dwelling men and women.
Design
Cross-sectional study assessing associations between self-reported BADL and IADL difficulty and MMSE scores for race/sex specific groups.
Setting
Homes of community-dwelling older adults.
Participants
A random sample of 974 African American and non-Hispanic White Medicare beneficiaries age 65 years and older living in west-central Alabama, participating in the University of Alabama at Birmingham (UAB) Study of Aging, but excluding those with reported diagnoses of dementia or with missing data.
Measurements
Function, based on self-reported difficulty in performing Basic and Instrumental Activities of Daily Living (BADL and IADL); Cognition, using the Mini-Mental State Exam (MMSE); Multivariable, linear regression models were used to test the association of function and cognition by race and sex-specific groups after adjusting for covariates.
Results
MMSE scores were modestly correlated with BADL and IADL in all four race/sex-specific group with Pearson r values ranging from −0.189 for non-Hispanic white women and −0.429 for African American men. Correlations of MMSE with BADL or IADL difficulty in any of the race/sex-specific groups were no longer significant after controlling for socio-demographic factors and comorbidities.
Conclusion
MMSE was not significantly associated with functional difficulty among older African American and non-Hispanic white men and women in the Deep South after adjusting for socio-demographic factors and comorbidities, suggesting a mediating role in the relationship between cognition and function.
PMCID: PMC3909884  PMID: 24479147
function; basic and instrumental activities of daily living; cognitive screening; MMSE; race, ethnicity, sex, and gender differences
4.  Impairment of activities of daily living and incident heart failure in community-dwelling older adults 
European Journal of Heart Failure  2012;14(6):581-587.
Aims
Instrumental activities of daily living (IADLs) are tasks that are necessary for independent community living. These tasks often require intact physical and cognitive function, the impairment of which may adversely affect health in older adults. In the current study, we examined the association between IADL impairment and incident heart failure (HF) in community-dwelling older adults.
Methods and results
Of the 5795 community-dwelling adults, aged ≥65 years, in the Cardiovascular Health Study, 5511 had data on baseline IADL and were free of prevalent HF. Of these, 1333 (24%) had baseline IADL impairment, defined as self-reported difficulty with one or more of the following tasks: using the telephone, preparing food, performing light and heavy housework, managing finances, and shopping. Propensity scores for IADL impairment, estimated for each of the 5511 participants, were used to assemble a cohort of 1038 pairs of participants with and without IADL impairment who were balanced on 42 baseline characteristics. Centrally adjudicated incident HF occurred in 26% and 21% of matched participants with and without IADL impairment, respectively, during >12 years of follow-up [matched hazard ratio (HR) 1.33; 95% confidence interval (CI) 1.11–1.59; P = 0.002]. Unadjusted and multivariable-adjusted HRs for incident HF before matching were 1.77 (95% CI 1.56–2.01; P < 0.001) and 1.33 (95% CI 1.15–1.54; P < 0.001), respectively. IADL impairment was also associated with all-cause mortality (matched HR 1.19; 95% CI 1.06–1.34; P = 0.004).
Conclusion
Among community-dwelling older adults free of baseline HF, IADL impairment is a strong and independent predictor of incident HF and mortality.
doi:10.1093/eurjhf/hfs034
PMCID: PMC3359859  PMID: 22492539
Instrumental activities of daily living; Incident heart failure; Propensity score
5.  High “Normal” Blood Glucose Is Associated with Decreased Brain Volume and Cognitive Performance in the 60s: The PATH through Life Study 
PLoS ONE  2013;8(9):e73697.
Context
Type 2 diabetes is associated with cerebral atrophy, cognitive impairment and dementia. We recently showed higher glucose levels in the normal range not to be free of adverse effects and to be associated with greater hippocampal and amygdalar atrophy in older community-dwelling individuals free of diabetes.
Objective
This study aimed to determine whether blood glucose levels in the normal range (<6.1 mmol/L) were associated with cerebral volumes in structures other than the hippocampus and amygdale, and whether these glucose-related regional volumes were associated with cognitive performance.
Design, Setting and Participants
210 cognitively healthy individuals (68–73 years) without diabetes, glucose intolerance or metabolic syndrome were assessed in the large, community-based Personality and Total Health Through Life (PATH) study.
Main Outcome Measure
Baseline blood glucose levels in the normal range (3.2–6.1 mmol/l) were used to determine regional brain volumes and associated cognitive function at wave 3.
Results
Higher blood glucose levels in the normal range were associated with lower grey/white matter regional volumes in the frontal cortices (middle frontal gyrus, inferior frontal gyrus precentral gyrus). Moreover, identified cerebral regions were associated with poorer cognitive performance and the structure-function associations were gender specific to men.
Conclusion
These findings stress the need to re-evaluate what is considered as healthy blood glucose levels, and consider the role of higher normal blood glucose as a risk factor for cerebral health, cognitive function and dementia. A better lifetime management of blood glucose levels may contribute to improved cerebral and cognitive health in later life and possibly protect against dementia.
doi:10.1371/journal.pone.0073697
PMCID: PMC3762736  PMID: 24023897
6.  Mild cognitive deficits and everyday functioning among older adults in the community: The Monongahela-Youghiogheny Healthy Aging Team (MYHAT) Study 
Objective
A key component of successful aging in old age is the ability to independently perform instrumental activities of daily living (IADLs). We examined the ability to perform multiple IADL tasks in relation to mild cognitive impairment (MCI) defined on purely neuropsychological grounds.
Design
Cross-sectional study.
Setting
Population-based cohort in Southwestern Pennsylvania.
Participants
1,737 community-dwelling adults aged 65 years and older.
Measurements
Classification of MCI based on performance with reference to norms in the cognitive domains of memory, language, attention, executive and visuospatial function. The ability to perform seven IADL tasks (travel, shopping, meal preparation, housework, taking medications, handling personal finances, and telephone use) as assessed by the Older Americans Resources and Services (OARS) scale.
Results
Those with cognitively defined MCI were more likely to be dependent in at least one IADL task, and in each individual IADL task, than cognitively normal participants. Better memory and executive functioning were associated with lower odds of IADL dependence in MCI. Across the subtypes of MCI, those with the multiple-domain amnestic subtype were the most likely to be dependent in all IADL tasks; with better executive functioning associated with lower risk of dependence in select IADL tasks in this group.
Conclusions
Mild impairment in cognition is associated with difficulty performing IADL tasks at the population level. Understanding these associations may help improve prediction of the outcomes of MCI. It may also allow appropriate targeting of cognitive interventions in MCI to potentially help preserve functional independence.
doi:10.1097/JGP.0b013e3182423961
PMCID: PMC3445790  PMID: 22337146
cognition; mild cognitive impairment; everyday functioning; instrumental activities of daily living; epidemiology; community; population
7.  Effects of Varying Diagnostic Criteria on Prevalence of Mild Cognitive Impairment in a Community Based Sample 
Mild cognitive impairment (MCI) is proposed to be a prodrome to dementia in some older adults. However, the presentation of MCI in the community can differ substantially from clinic-based samples. The aim of the current study is to demonstrate the effects of different operational definitions of MCI on prevalence estimates in community-dwelling older adults. A consecutive series of 200 participants aged 65 and over from the Adult Changes in Thought (ACT) community-based cohort were approached to undergo comprehensive neuropsychological and medical evaluation; 159 were included in the final analyses. Nondemented subjects were categorized using various diagnostic criteria for MCI. In a novel approach, neuropsychological test scores were evaluated using an individualized benchmark as a point of test comparison, as well as traditional methods that entail comparison to age-based normative data. Diagnostic criteria were further subdivided by severity of impairment (1.0 vs. 1.5 standard deviations [sd] below the benchmark) and extent of impairment (based on a single test or an average of tests within a cognitive domain). MCI prevalence rates in the sample were highly dependent on these diagnostic factors, and varied from 11% to 92% of the sample. Older groups tended to show higher prevalence rates, although this was not the case across all diagnostic schemes. The use of an individualized benchmark, less severe impairment cutoff, and impairment on only a single test all produced higher rates of MCI. Longitudinal follow-up will determine whether varying diagnostic criteria improves sensitivity and specificity of the MCI diagnosis as a predictor for dementia.
doi:10.3233/JAD-2011-101821
PMCID: PMC3146555  PMID: 21368379
Age related memory disorders; aging; cognition; Alzheimer's disease; dementia; diagnosis; epidemiology; individual differences; neuropsychological tests; prevalence; normative
8.  Vitamin B12, cognition, and brain MRI measures 
Neurology  2011;77(13):1276-1282.
Objective:
To investigate the interrelations of serum vitamin B12 markers with brain volumes, cerebral infarcts, and performance in different cognitive domains in a biracial population sample cross-sectionally.
Methods:
In 121 community-dwelling participants of the Chicago Health and Aging Project, serum markers of vitamin B12 status were related to summary measures of neuropsychological tests of 5 cognitive domains and brain MRI measures obtained on average 4.6 years later among 121 older adults.
Results:
Concentrations of all vitamin B12–related markers, but not serum vitamin B12 itself, were associated with global cognitive function and with total brain volume. Methylmalonate levels were associated with poorer episodic memory and perceptual speed, and cystathionine and 2-methylcitrate with poorer episodic and semantic memory. Homocysteine concentrations were associated with decreased total brain volume. The homocysteine-global cognition effect was modified and no longer statistically significant with adjustment for white matter volume or cerebral infarcts. The methylmalonate-global cognition effect was modified and no longer significant with adjustment for total brain volume.
Conclusions:
Methylmalonate, a specific marker of B12 deficiency, may affect cognition by reducing total brain volume whereas the effect of homocysteine (nonspecific to vitamin B12 deficiency) on cognitive performance may be mediated through increased white matter hyperintensity and cerebral infarcts. Vitamin B12 status may affect the brain through multiple mechanisms.
doi:10.1212/WNL.0b013e3182315a33
PMCID: PMC3179651  PMID: 21947532
9.  Specific Measures of Executive Function Predict Cognitive Decline in Older Adults 
Decline in executive function has been noted in the prodromal stage of Alzheimer’s disease (AD) and may presage more global cognitive declines. In this prospective longitudinal study, five measures of executive function were used to predict subsequent global cognitive decline in initially nondemented older adults. Of 71 participants, 15 demonstrated significant decline over a 1-year period on the Dementia Rating Scale (Mattis, 1988) and the remaining participants remained stable. In the year before decline, the decline group performed significantly worse than the no-decline group on two measures of executive function: the Color-Word Interference Test (CWIT; inhibition/switching condition) and Verbal Fluency (VF; switching condition). In contrast, decliners and non-decliners performed similarly on measures of spatial fluency (Design Fluency switching condition), spatial planning (Tower Test), and number-letter switching (Trail Making Test switching condition). Furthermore, the CWIT inhibition-switching measure significantly improved the prediction of decline and no-decline group classification beyond that of learning and memory measures. These findings suggest that some executive function measures requiring inhibition and switching provide predictive utility of subsequent global cognitive decline independent of episodic memory and may further facilitate early detection of dementia.
doi:10.1017/S1355617711001524
PMCID: PMC3314335  PMID: 22115028
Executive functions; Global cognition; Switching; Prodromal Alzheimer’s disease; Mild cognitive impairment; Prediction
10.  Associations between Level and Change in Physical Function and Brain Volumes 
PLoS ONE  2013;8(11):e80386.
Background
Higher levels of fitness or physical function are positively associated with cognitive outcomes but the potential underlying mechanisms via brain structure are still to be elucidated in detail. We examined associations between brain structure and physical function (contemporaneous and change over the previous three years) in community-dwelling older adults.
Methodology/Principal Findings
Participants from the Lothian Birth Cohort 1936 (N=694) underwent brain MRI at age 73 years to assess intracranial volume, and the volumes of total brain tissue, ventricles, grey matter, normal-appearing white matter, and white matter lesions. At ages 70 and 73, physical function was assessed by 6-meter walk, grip strength, and forced expiratory volume. A summary ‘physical function factor’ was derived from the individual measures using principal components analysis. Performance on each individual physical function measure declined across the three year interval (p<0.001). Higher level of physical function at ages 70 and 73 was associated with larger total brain tissue and white matter volumes, and smaller ventricular and white matter lesion volumes (standardized β ranged in magnitude from 0.07 to 0.17, p<0.001 to 0.034). Decline in physical function from age 70 to 73 was associated with smaller white matter volume (0.08, p<0.01, though not after correction for multiple testing), but not with any other brain volumetric measurements.
Conclusions/Significance
Physical function was related to brain volumes in community-dwelling older adults: declining physical function was associated with less white matter tissue. Further study is required to explore the detailed mechanisms through which physical function might influence brain structure, and vice versa.
doi:10.1371/journal.pone.0080386
PMCID: PMC3827194  PMID: 24265818
11.  The Adverse Impact of Type 2 Diabetes on Brain Volume in Heart Failure 
Objective
Heart failure (HF) is associated with structural brain abnormalities, including atrophy in multiple brain regions. Type 2 diabetes mellitus (T2DM) is a prevalent comorbid condition in HF and is associated with abnormalities on neuroimaging in other medical and elderly samples. The current study examined whether comorbid T2DM exacerbates brain atrophy in older adults with HF.
Methods
Seventy-five older adults with HF underwent echocardiogram, and completed a brief cognitive test battery. Participants then underwent brain magnetic resonance imaging (MRI) to quantify total brain volumes, cortical lobar volumes, and white matter hyperintensities (WMH).
Results
Approximately 30% of HF patients had a comorbid T2DM diagnosis. A series of MANCOVA analyses adjusting for medical and demographic characteristics and intracranial volume showed that HF patients with T2DM had smaller total brain, gray matter, and subcortical gray matter volume than those without such history. No between group differences emerged for WMH. Persons with T2DM also had smaller cortical lobar volumes, including in frontal, temporal, and parietal lobes. Follow-up analyses revealed smaller total and cortical lobar brain volumes and WMH were associated with poorer performance on measures of global cognitive status, attention, executive functions, and memory.
Conclusions
T2DM is associated with smaller total and cortical lobar brain volumes in patients with HF and these structural brain indices were associated with cognitive test performance. Prospective studies that directly monitor glucose levels are needed to confirm our findings and clarify the mechanisms by which T2DM adversely impacts brain atrophy in this population.
doi:10.1080/13803395.2013.771617
PMCID: PMC3633205  PMID: 23419083
Brain; cognitive function; heart failure; type 2 diabetes; neuroimaging
12.  Differential Benefits of Memory Training for Minority Older Adults in the SeniorWISE Study 
The Gerontologist  2010;50(5):632-645.
Purpose: Cognitive training improves mental abilities in older adults, but the benefit to minority elders is unclear. We conducted a subgroup analysis of subjects in the SeniorWISE (Wisdom Is Simply Exploration) trial to examine this issue. Design and Methods: SeniorWISE was a Phase 3 randomized trial that enrolled 265 nondemented community-dwelling older adults aged 65 years and older between 2001 and 2006. Participants were randomly assigned to 12 hr of either memory or health training. Results: The sample was 79% female, 71% Caucasian, 17% Hispanic, and 12% African American. On the Rivermead Behavioural Memory Test (RBMT), 28% of the sample scored normal, 47% scored poor, and 25% impaired. Memory performance changed differently over time depending on the demographic characteristics of participants. Both Hispanics and Blacks performed better than Whites on visual memory, and Blacks performed better over time on instrumental activities of daily living. On all performance measures, lower pretest scores were associated with relatively greater improvements over time. Implications: Our analyses suggested that minority participants received differential benefits from the memory training; however, this remains speculative because the 3 ethnic groups in the sample were not equivalent in size. The question of why Black and Hispanic participants often made greater improvements needs further exploration.
doi:10.1093/geront/gnq017
PMCID: PMC2948826  PMID: 20203096
Differential benefits of training; Minority elderly adults; Memory training; Cognitive performance
13.  Everyday Cognition: Age and Intellectual Ability Correlates 
Psychology and aging  1999;14(4):627-644.
The primary aim of this study was to examine the relationship between a new battery of everyday cognition measures, which assessed 4 cognitive abilities within 3 familiar real-world domains, and traditional psychometric tests of the same basic cognitive abilities. Several theoreticians have argued that everyday cognition measures are somewhat distinct from traditional cognitive assessment approaches, and the authors investigated this assertion correlationally in the present study. The sample consisted of 174 community-dwelling older adults from the Detroit metropolitan area, who had an average age of 73 years. Major results of the study showed that (a) each everyday cognitive test was strongly correlated with the basic cognitive abilities; (b) several basic abilities, as well as measures of domain-specific knowledge, predicted everyday cognitive performance; and (c) everyday and basic measures were similarly related to age. The results suggest that everyday cognition is not unrelated to traditional measures, nor is it less sensitive to age-related differences.
PMCID: PMC2904910  PMID: 10632150
14.  Vascular Burden and Cognitive Functioning in Depressed Older Adults 
Background
Vascular burden is known to contribute to geriatric depression and cognitive impairment. The objective of our study was to evaluate the relationship between vascular burden and pattern of cognitive impairment in older adults with depression.
Methods
Ninety-four community-dwelling older adults (mean age = 70.8 years; SD = 7.63) diagnosed with major depression were recruited to participate in the tai chi complementary use study aimed to improve antidepressant response to an antidepressant medication. All participants received comprehensive evaluations of depression, apathy, and vascular risk factors, and completed a battery of cognitive measures of memory, cognitive control, verbal fluency, and attention.
Results
The severity of vascular burden was significantly correlated with depression severity and impaired performance on measures of cognitive control (i.e., inhibition/mental flexibility), and attention, but not memory or verbal fluency. Neither the severity of comorbid apathy nor medical illness burden was related to cognitive impairment.
Conclusions
Vascular burden in older depressed adults contributes to cognitive impairment, particularly in domains of attention and cognitive control. Our findings suggest that aggressive treatment of vascular risk factors may reduce risk for further cognitive decline in depressed older adults.
doi:10.1097/JGP.0b013e31822ccd64
PMCID: PMC3889859  PMID: 21857219
Cerebrovascular risk factors; cognitive impairment; geriatric depression; vascular disease
15.  Medial Temporal Lobe Volume Predicts Elders' Everyday Memory 
Psychological science  2013;24(7):1113-1122.
Deficits in memory for everyday activities are common complaints among healthy and demented older adults. The medial temporal lobes and dorsolateral prefrontal cortex are both affected by aging and early-stage Alzheimer's disease, and are known to influence performance on laboratory memory tasks. We investigated whether the volume of these structures predicts everyday memory. Cognitively healthy older adults and older adults with mild Alzheimer's-type dementia watched movies of everyday activities and completed memory tests on the activities. Structural MRI was used to measure brain volume. Medial temporal but not prefrontal volume strongly predicted subsequent memory. Everyday memory depends on segmenting activity into discrete events during perception, and medial temporal volume partially accounted for the relationship between performance on the memory tests and performance on an event-segmentation task. The everyday-memory measures used in this study involve retrieval of episodic and semantic information as well as working memory updating. Thus, the current findings suggest that during perception, the medial temporal lobes support the construction of event representations that determine subsequent memory.
doi:10.1177/0956797612466676
PMCID: PMC3936320  PMID: 23630222
perception; memory; cognitive neuroscience; aging
16.  Profile of hippocampal volumes and stroke risk varies by neuropsychological definition of mild cognitive impairment 
Wide-ranging conceptual and diagnostic approaches to defining mild cognitive impairment (MCI) have led to highly variable prevalence and progression rates. We sought to examine whether bilateral hippocampal volumes and cerebrovascular risk factors in individuals characterized by two different neuropsychological definitions of MCI subtypes would also differ. Participants were 65 nondemented, community-dwelling, older adults, ages 62–91 years, drawn from a larger group of individuals enrolled in a longitudinal study of normal aging. A comprehensive neuropsychological definition of MCI that required the presence of more than one impaired score in a cognitive domain resulted in expected anatomical results; hippocampal volumes were significantly smaller in the aMCI group as compared to cognitively normal or nonamnestic MCI participants. However, a typical definitional scheme for classifying MCI based only on the presence of one impaired score within a cognitive domain did not result in hippocampal differences between groups. Global stroke risk factors did not differ between the two definitional schemes, although the relationship between stroke risk variables and neuropsychological performance did vary by diagnostic approach. The comprehensive approach demonstrated associations between stroke risk and cognition, whereas the typical approach did not. Use of more sophisticated clinical decision-making and diagnostic approaches that incorporate comprehensive neuropsychological assessment techniques is supported by this convergence of neuropsychological, neuropathological, and stroke risk findings.
doi:10.1017/S1355617709090638
PMCID: PMC2864786  PMID: 19570306
Mild cognitive impairment; Neuroimaging; Neuropsychology; Older adults; Memory; Executive functioning; Stroke risk; Diagnosis; Amnestic; Nonamnestic
17.  Quantification of five neuropsychological approaches to defining mild cognitive impairment 
Objectives
Operational definitions of cognitive impairment have varied widely in diagnosing mild cognitive impairment (MCI). Identifying clinical subtypes of MCI has further challenged diagnostic approaches, since varying the components of the objective cognitive assessment can significantly impact diagnosis. Therefore, we investigated the applicability of diagnostic criteria for clinical subtypes of MCI in a naturalistic research sample of community elders and quantified the variability in diagnostic outcomes that results from modifying the neuropsychological definition of objective cognitive impairment.
Design
Cross-sectional and longitudinal study
Setting
San Diego, CA, Veterans Administration Hospital
Participants
90 nondemented, neurologically normal, community-dwelling older adults were initially assessed and 73 were seen for follow-up approximately 17 months later.
Measurements
Participants were classified via consensus diagnosis as either normally aging or having MCI via each of five diagnostic strategies, which varied the cutoff for objective impairment as well as the number of neuropsychological tests considered in the diagnostic process.
Results
A range of differences in the percentages identified as MCI versus cognitively normal were demonstrated, depending on the classification criteria employed. A substantial minority of individuals demonstrated diagnostic instability over time as well as across diagnostic approaches. The single domain non-amnestic subtype diagnosis was particularly unstable (e.g., prone to reclassification as normal at follow up).
Conclusion
Our findings provide empirical support for a neuropsychologically derived operational definition of clinical subtypes of MCI and point to the importance of using comprehensive neuropsychological assessments. Diagnoses, particularly involving non-amnestic MCI, were variable over time. The applicability and utility of this particular MCI subtype warrants further investigation.
doi:10.1097/JGP.0b013e31819431d5
PMCID: PMC2743175  PMID: 19390294
mild cognitive impairment; clinical subtypes; neuropsychology; diagnosis; longitudinal
18.  Neuropsychological Predictors of Dementia in Late-Life Major Depressive Disorder 
Objective
Major Depressive Disorder (MDD) is a likely risk factor for dementia, but some cases of MDD in older adults may actually represent a prodrome of this condition. The purpose of this study was to use neuropsychological test scores to predict conversion to dementia in a sample of depressed older adults diagnosed as nondemented at time of neuropsychological testing.
Design
Longitudinal, with mean follow-up of 5.45 years.
Setting
Outpatient depression treatment study at Duke University
Participants
30 nondemented individuals depressed at time of neuropsychological testing and later diagnosed with incident dementia; 149 nondemented individuals depressed at time of neuropsychological testing and a diagnosis of cognitively normal.
Methodology
All participants received clinical assessment of depression, were assessed to rule out prevalent dementia at time of study enrollment, completed neuropsychological testing at time of study enrollment, and were diagnosed for cognitive disorders on an annual basis.
Results
Non-demented, acutely depressed older adults who converted to dementia during the study period exhibited broadly lower cognitive performances at baseline than acutely depressed individuals who remained cognitively normal. Discriminant function analysis indicated that 2 neuropsychological tests, CERAD Recognition Memory and Trail Making B, best predicted dementia conversion.
Conclusions
Depressed older adults with cognitive deficits in the domains of memory and executive functions during acute depression are at higher risk for developing dementia. Some cases of late-life depression may reflect a prodrome of dementia in which clinical manifestation of mood changes may co-occur with emerging cognitive deficits.
doi:10.1016/j.jagp.2012.12.009
PMCID: PMC3376682  PMID: 23395197
geriatric depression; dementia; neuropsychology; memory; executive function
19.  Neuropathologic correlates of cognition in a population-based sample 
Many cognitively normal older adults have underlying neuropathologic changes of Alzheimer’s disease (AD), vascular brain injury (VBI), or Lewy body disease (LBD), which confer an increased risk of dementia. The current study focused on the association between multiple neuropathologic indices and performance on specific cognitive domains in a community sample of older adults. Of 438 participants in the Adult Changes in Thought population-based study of brain aging who were autopsied, 363 subjects had cognitive testing at their final study visit and were included. Associations were measured between performance on the Cognitive Abilities Screening Instrument prior to death and neuropathologic endpoints, including AD neuropathologic changes, LBD, cerebral amyloid angiopathy, and measures of VBI. Braak stage for neurofibrillary tangles, lower brain weight, and VBI as measured by cerebral cortical microvascular lesions (μVBI) explained a significant proportion of the variance associated with global cognitive test performance (R2=0.31, p< 0.0001) both in the entire sample and when analysis was restricted to non-demented subjects (R2= 0.23, p< 0.0001). Specific cognitive domains were differentially related to neuropathologic lesion type: memory and executive function with AD pathologic changes and cortical μVBI, executive function with subcortical μVBI, and visuospatial construction with LBD. Thus, neuropathologic lesions of LBD and μVBI are associated with poorer cognitive performance over and above AD neuropathologic changes in subjects without dementia in this cohort. These findings underscore that cognitive impairment is a complex convergent trait that has important implications for clinical investigation and medical management of older adults.
doi:10.3233/JAD-130281
PMCID: PMC3737376  PMID: 23666176
Alzheimer’s disease; brain; cerebrovascular disorders; cognition; dementia; Lewy bodies; pathologic processes
20.  Poor balance and lower gray matter volume predict falls in older adults with mild cognitive impairment 
BMC Neurology  2013;13:102.
Background
The risk of falling is associated with cognitive dysfunction. Older adults with mild cognitive impairment (MCI) exhibit an accelerated reduction of brain volume, and face an increased risk of falling. The current study examined the relationship between baseline physical performance, baseline gray matter volume and falls during a 12-month follow-up period among community-dwelling older adults with MCI.
Methods
Forty-two older adults with MCI (75.6 years, 43% women) underwent structural magnetic resonance imaging and baseline physical performance assessment, including knee-extension strength, one-legged standing time, and walking speed with normal pace. ‘Fallers’ were defined as people who had one or more falls during the 12-month follow-up period.
Results
Of the 42 participants, 26.2% (n = 11) experienced at least one fall during the 12-month follow-up period. Fallers exhibited slower walking speed and shorter one-legged standing time compared with non-fallers (both p < .01). One-legged standing time (sec) (standardized odds ratio [95% confidence interval]: 0.89 [0.81, 0.98], p = .02) was associated with a significantly lower rate of falls during the 12-month follow-up after adjusting for age, sex, body mass index, and history of falling in the past year at baseline. Voxel-based morphometry was used to examine differences in baseline gray matter volume between fallers and non-fallers, revealing that fallers exhibited a significantly greater reduction in the bilateral middle frontal gyrus and superior frontal gyrus.
Conclusions
Poor balance predicts falls over 12 months, and baseline lower gray matter densities in the middle frontal gyrus and superior frontal gyrus were associated with falls in older adults with MCI. Maintaining physical function, especially balance, and brain structural changes through many sorts of prevention strategies in the early stage of cognitive decline may contribute to decreasing the risk of falls in older adults with MCI.
doi:10.1186/1471-2377-13-102
PMCID: PMC3750260  PMID: 23915144
21.  Cognitive Correlates of Functional Performance in Older Adults: Comparison of Self-Report, Direct Observation, and Performance-Based Measures 
Neuropsychologists are often asked to answer questions about the effects of cognitive deficits on everyday functioning. This study examined the relationship between and the cognitive correlates of self-report, performance-based, and direct observation measures commonly used as proxy measures for everyday functioning. Participants were 88 community-dwelling, cognitively healthy older adults (age 50–86 years). Participants completed standardized neuropsychological tests and questionnaires, and performed eight activities of daily living (e.g., water plants, fill a medication dispenser) while under direct observation in a campus apartment. All proxy measures of everyday function were sensitive to the effects of healthy cognitive aging. After controlling for age, cognitive predictors explained a unique amount of the variance for only the performance-based behavioral simulation measure (i.e., Revised Observed Tasks of Daily Living). The self-report instrumental activities of daily living (IADL) and the performance-based everyday problem-solving test (i.e., EPT) did not correlate with each other; however, both were unique predictors of the direct observation measure. These findings suggest that neuropsychologists must be cautious in making predictions about the quality of everyday activity completion in cognitively healthy older adults from specific cognitive functions. The findings further suggest that a self-report of IADLs and the performance-based EPT may be useful measures for assessing everyday functional status in cognitively healthy older adults.
doi:10.1017/S1355617711000865
PMCID: PMC3736729  PMID: 21729400
Activities of daily living; Cognitive correlates; Functional status; Aging; Instrumental activities of daily living; Everyday functioning
22.  Everyday Cognition in older adults 
The recently developed Everyday Cognition scales (ECog) measure multiple cognitively-relevant functional domains (e.g. Everyday Memory, Everyday Language, Everyday Visuospatial abilities and three everyday executive domains). The present study further evaluated the validity of the ECog by examining its relationship with objective measures of neuropsychological function, and neurobiological markers of disease as reflected by structural neuroimaging. Participants included 474 older adults (244 normals, 142 with MCI, 88 with dementia). The neuropsychological domains measured were episodic memory, semantic memory, spatial ability, and executive functioning. Brain MRI volumes included total brain (BV), hippocampus (HC) and dorsolateral prefrontal cortex (DLPFC). Neuropsychological measures of episodic memory and executive function were most consistently related to the ECog domains; spatial abilities had a specific relationship to the Everyday Visuospatial ECog domain. HC and BV volumes were related to most ECog domains, while DLPFC volume was independently related to two everyday executive domains (Everyday Planning and Everyday Organization). The pattern of associations varied somewhat as a function of diagnosis. Episodic memory and HC had more consistent associations with the ECog domains in older adults with MCI/dementia than in cognitively normal elderly.
doi:10.1017/S1355617712001609
PMCID: PMC3818105  PMID: 23369894
Activities of daily living; Instrumental Activities of daily living; Functional abilities; MCI; Dementia; Neuroimaging; Episodic memory; Executive function
23.  Sleep Onset/Maintenance Difficulties and Cognitive Function in Nondemented Older Adults: the Role of Cognitive Reserve 
Background
This study examined the relationship between cognitive function and sleep onset/maintenance difficulties (SO/MD) in nondemented older adults. We hypothesized that SO/MD negatively impacts cognition and that older adults with lower education would be especially vulnerable to its effects.
Methods
The sample comprised 549 older adults from the Einstein Aging Study (EAS), a community-based sample. Participants completed neuropsychological assessment and a sleep questionnaire. Univariate ANCOVAs were performed with cognitive performance as a dependent variable, SO/MD (present or absent) and education (lower:≤12 years; higher:>12 years) as between-subjects factors, and age, ethnicity, gender, depression, and cardiovascular comorbidies as covariates.
Results
Participants were an average age of 79.7±5.0 years (range=71–97). Fifty-seven percent (n=314) of the sample met criteria for SO/MD. Among participants with SO/MD, those with lower education performed more poorly on a test of category fluency than participants with higher education (means: 35.2 vs. 41.0, p<0.001); among older adults without SO/MD, educational attainment had no measurable effect on cognition (SO/MD × education interaction (F(1,536)=14.5, p=0.00)).
Conclusions
Consistent with the cognitive reserve hypothesis, older adults with lower education appear selectively vulnerable to the negative effects of sleep onset/maintenance difficulties on tests of verbal fluency.
doi:10.1017/S1355617711001901
PMCID: PMC3682475  PMID: 22317892
Sleep; Neuropsychology; Cognitive Reserve; Elderly; Education; Depression
24.  Longitudinal Changes in Memory and Executive Functioning are Associated with Longitudinal Change in Instrumental Activities of Daily Living in older adults 
The Clinical neuropsychologist  2008;23(3):446-461.
Impaired everyday function is a diagnostic criterion for dementia, and a determinant of healthcare utilization and caregiver burden. Although many previous studies have demonstrated a cross-sectional relationships between cognition (particularly executive functions and memory) and everyday function in older adults, very little is known about longitudinal relationships between these domains. This study examined the association between longitudinal change in episodic memory (MEM) and executive functioning (EXEC) and change in everyday function. Participants were a cognitively heterogeneous group of 100 elderly persons including those with normal cognition, as well as those with mild cognitive impairment and dementia. They were followed for an average of five years. Random effects modeling showed that change in both MEM and EXEC were independently associated with rate of change in informant-rated instrumental activities of daily living (IADLs), even after controlling for age, education, and gender. Findings indicate that declines in MEM and EXEC over time make unique and independent contributions to declines in older adults’ ability to function in daily life.
doi:10.1080/13854040802360558
PMCID: PMC2881703  PMID: 18821181
Memory; Executive functioning; Everyday Function; dementia; Alzheimer’s disease
25.  Longitudinal Relationships between Subjective Fatigue, Cognitive Function, and Everyday Functioning in Old Age 
Background
The present study examined the prospective relationships between subjective fatigue, cognitive function, and everyday functioning.
Methods
A cohort study with secondary data analysis was conducted using data from 2,781 community-dwelling older adults without dementia who were enrolled to participate in the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) randomized intervention trial. Measures included demographic and health information at baseline, and annual assessments of subjective fatigue, cognitive function (i.e., speed of processing, memory, and reasoning), and everyday functioning (i.e., everyday speed and everyday problem-solving) over 5 years.
Results
Four distinct classes of subjective fatigue were identified using growth mixture modeling: one group complaining fatigue “some of the time” at baseline but “most of the time” at 5-year follow-up (increased fatigue), one complaining fatigue “a good bit of the time” constantly over time (persistent fatigue), one complaining fatigue “most of the time” at baseline but “some of the time” at 5-year follow-up (decreased fatigue), and the fourth complaining fatigue “some of the time” constantly over time (persistent energy). All domains of cognitive function and everyday functioning declined significantly over five years; and the decline rates, but not the baseline levels, differed by the latent class of subjective fatigue. Except for the decreased fatigue class, there were different degrees of significant associations between the decline rates of subjective fatigue and all domains of cognitive function and everyday functioning in other classes of subjective fatigue.
Conclusion
Future interventions should address subjective fatigue when managing cognitive and functional abilities in community-dwelling older adults.
doi:10.1017/S1041610212001718
PMCID: PMC3552486  PMID: 23083533
subjective fatigue; cognition; everyday functioning; ACTIVE

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