Ozioma C. Okonkwo

Mild Cognitive Impairment and Everyday Function: Evidence of Reduced Speed in Performing Instrumental Activities of Daily Living

Objective Mild cognitive impairment (MCI) may involve subtle functional losses that are not detected with typical self- or informant-report assessments of daily function. Information about the nature of functional difficulties in MCI can be used to augment common clinical assessment procedures, and aspects of function that are affected in MCI can serve as meaningful endpoints for intervention trials. Design Cross-sectional case and comparison group study. Setting University medical center. Participants Fifty participants with MCI and 59 cognitively normal participants. Measurements The authors compared the groups on dimensions of both speed and accuracy in performing instrumental activities of daily living (IADLs), using a standardized Timed IADL measure that evaluates five functional domains commonly encountered in everyday life (telephone use, locating nutrition information on food labels, financial abilities, grocery shopping, medication management). Results Across Timed IADL domains, MCI participants demonstrated accuracy comparable with cognitively normal participants but took significantly longer to complete the functional activities, controlling for depressive symptoms (p Conclusion These results suggest that slower speed of task performance is an important component and perhaps an early marker of functional change in MCI that would not be detected using traditional measurements of daily function. Future research should address the question of whether performance-based functional measures, as well as simple queries regarding whether functional activities take longer than usual to complete, may improve the prediction of future cognitive decline and disease progression among those individuals in whom MCI represents impending dementia.

Medical decision-making capacity in patients with mild cognitive impairment

Objectives: To empirically assess the capacity of patients with amnestic mild cognitive impairment (MCI) to consent to medical treatment under different consent standards (Ss). Methods: Participants were 56 healthy controls, 60 patients with MCI, and 31 patients with mild Alzheimer disease (AD). Each participant was administered the Capacity to Consent to Treatment Instrument (CCTI) and a comprehensive neuropsychological battery. Group differences in performance on the CCTI and neuropsychological variables were examined. In addition, the capacity status (capable, marginally capable, or incapable) of each MCI participant on each CCTI standard was examined using cut scores derived from control performance. Results: Patients with MCI performed comparably to controls on minimal consent standards requiring merely expressing a treatment choice (S1) or making the reasonable treatment choice [S2], but significantly below controls on the three clinically relevant standards of appreciation (S3), reasoning (S4), and understanding (S5). In turn, the MCI group performed significantly better than the mild AD group on [S2], S4, and S5. Regarding capacity status, patients with MCI showed a progressive pattern of capacity compromise (marginally capable and incapable outcomes) related to stringency of consent standard. Conclusions: Patients with amnestic mild cognitive impairment (MCI) demonstrate significant impairments on clinically relevant abilities associated with capacity to consent to treatment. In obtaining informed consent, clinicians and researchers working with patients with MCI must consider the likelihood that many of these patients may have impairments in consent capacity related to their amnestic disorder and related cognitive impairments. GLOSSARY: AD = Alzheimer disease; ADRC = Alzheimers Disease Research Center; CCTI = Capacity to Consent to Treatment Instrument; CVLT-II = California Verbal Learning Test, second edition; DRS-2 = Dementia Rating Scale, 2nd edition; GDS = Geriatric Depression Scale; MCI = mild cognitive impairment; MDC = medical decision-making capacity; MMSE = Mini-Mental State Examination; Ss = consent standards; WAIS-III = Wechsler Adult Intelligence Scale, third edition; WMS-III = Wechsler Memory Scale, third edition; WMS-R = Wechsler Memory Scale, revised edition; WRAT-3 = Wide Range Achievement Test, third edition.

Association of Insulin Resistance With Cerebral Glucose Uptake in Late Middle–Aged Adults at Risk for Alzheimer Disease

IMPORTANCE Converging evidence suggests that Alzheimer disease (AD) involves insulin signaling impairment. Patients with AD and individuals at risk for AD show reduced glucose metabolism, as indexed by fludeoxyglucose F 18-labeled positron emission tomography (FDG-PET). OBJECTIVES To determine whether insulin resistance predicts AD-like global and regional glucose metabolism deficits in late middle-aged participants at risk for AD and to examine whether insulin resistance-predicted variation in regional glucose metabolism is associated with worse cognitive performance. DESIGN, SETTING, AND PARTICIPANTS This population-based, cross-sectional study included 150 cognitively normal, late middle-aged (mean [SD] age, 60.7 [5.8] years) adults from the Wisconsin Registry for Alzheimers Prevention (WRAP) study, a general community sample enriched for AD parental history. Participants underwent cognitive testing, fasting blood draw, and FDG-PET at baseline. We used the homeostatic model assessment of peripheral insulin resistance (HOMA-IR). Regression analysis tested the statistical effect of HOMA-IR on global glucose metabolism. We used a voxelwise analysis to determine whether HOMA-IR predicted regional glucose metabolism. Finally, predicted variation in regional glucose metabolism was regressed against cognitive factors. Covariates included age, sex, body mass index, apolipoprotein E ε4 genotype, AD parental history status, and a reference region used to normalize regional uptake. MAIN OUTCOMES AND MEASURES Regional glucose uptake determined using FDG-PET and neuropsychological factors. RESULTS Higher HOMA-IR was associated with lower global glucose metabolism (β = -0.29; P < .01) and lower regional glucose metabolism across large portions of the frontal, lateral parietal, lateral temporal, and medial temporal lobes (P < .05, familywise error corrected). The association was especially robust in the left medial temporal lobe (R2 = 0.178). Lower glucose metabolism in the left medial temporal lobe predicted by HOMA-IR was significantly related to worse performance on the immediate memory (β = 0.317; t148 = 4.08; P < .001) and delayed memory (β = 0.305; t148 = 3.895; P < .001) factor scores. CONCLUSIONS AND RELEVANCE Our results show that insulin resistance, a prevalent and increasingly common condition in developed countries, is associated with significantly lower regional cerebral glucose metabolism, which in turn may predict worse memory performance. Midlife may be a critical period for initiating treatments to lower peripheral insulin resistance to maintain neural metabolism and cognitive function.

Cognitive Correlates of Financial Abilities in Mild Cognitive Impairment

OBJECTIVES: To investigate the cognitive correlates of financial abilities in mild cognitive impairment (MCI).

Declining financial capacity in mild cognitive impairment A 1-year longitudinal study

Objective: To investigate 1-year change in financial capacity in relation to conversion from amnestic mild cognitive impairment (MCI) to dementia. Methods: Seventy-six cognitively healthy older controls, 25 patients with amnestic MCI who converted to Alzheimer-type dementia during the study period (MCI converters), and 62 patients with MCI who did not convert to dementia (MCI nonconverters) were administered the Financial Capacity Instrument (FCI) at baseline and 1-year follow-up. Performance on the FCI domain and global scores was compared within and between groups using multivariate repeated-measures analyses. Results: At baseline, controls performed better than MCI converters and nonconverters on almost all FCI domains and on both FCI total scores. MCI converters performed below nonconverters on domains of financial concepts, cash transactions, bank statement management, and bill payment and on both FCI total scores. At 1-year follow-up, MCI converters showed significantly greater decline than controls and MCI nonconverters for the domain of checkbook management and for both FCI total scores. The domain of bank statement management showed a strong trend. For both the checkbook and bank statement domains, MCI converters showed declines in procedural skills, such as calculating the correct balance in a checkbook register, but not in conceptual understanding of a checkbook or a bank statement. Conclusions: Declining financial skills are detectable in patients with mild cognitive impairment (MCI) in the year before their conversion to Alzheimer disease. Clinicians should proactively monitor patients with MCI for declining financial skills and advise patients and families about appropriate interventions.

Fornix integrity and hippocampal volume predict memory decline and progression to Alzheimer's disease

The fornix is the predominant outflow tract of the hippocampus, a brain region known to be affected early in the course of Alzheimers disease (AD). The aims of the present study were to: (1) examine the cross‐sectional relationship between fornix diffusion tensor imaging (DTI) measurements (fractional anisotropy [FA], mean diffusivity [MD], axial diffusivity, and radial diffusivity), hippocampal volume, and memory performance, and (2) compare fornix DTI measures with hippocampal volumes as predictors of progression and transition from amnestic mild cognitive impairment to AD dementia.

Amyloid burden and neural function in people at risk for Alzheimer's Disease

To determine the relationship between amyloid burden and neural function in healthy adults at risk for Alzheimers Disease (AD), we used multimodal imaging with [C-11]Pittsburgh compound B positron emission tomography, [F-18]fluorodeoxyglucose, positron emission tomography , and magnetic resonance imaging, together with cognitive measurement in 201 subjects (mean age, 60.1 years; range, 46-73 years) from the Wisconsin Registry for Alzheimers Prevention. Using a qualitative rating, 18% of the samples were strongly positive Beta-amyloid (Aβ+), 41% indeterminate (Aβi), and 41% negative (Aβ-). Aβ+ was associated with older age, female sex, and showed trends for maternal family history of AD and APOE4. Relative to the Aβ- group, Aβ+ and Aβi participants had increased glucose metabolism in the bilateral thalamus; Aβ+ participants also had increased metabolism in the bilateral superior temporal gyrus. Aβ+ participants exhibited increased gray matter in the lateral parietal lobe bilaterally relative to the Aβ- group, and no areas of significant atrophy. Cognitive performance and self report cognitive and affective symptoms did not differ between groups. Amyloid burden can be identified in adults at a mean age of 60 years and is accompanied by glucometabolic increases in specific areas, but not atrophy or cognitive loss. This asymptomatic stage may be an opportune window for intervention to prevent progression to symptomatic AD.

Amyloid burden is associated with self-reported sleep in nondemented late middle-aged adults

Midlife may be an ideal window for intervention in Alzheimers disease (AD). To determine whether sleep is associated with early signs of AD neuropathology (amyloid deposition) in late midlife, we imaged brain amyloid deposits using positron emission tomography with [C-11]Pittsburgh Compound B (PiB), and assessed sleep with the Epworth Sleepiness Scale and the Medical Outcomes Study Sleep Scale in 98 cognitively healthy adults (aged 62.4 ± 5.7 years) from the Wisconsin Registry for Alzheimers Prevention. We used multiple regressions to test the extent to which sleep scores predicted regional amyloid burden. Participants reporting less adequate sleep, more sleep problems, and greater somnolence on the Medical Outcomes Study had greater amyloid burden in AD-sensitive brain regions (angular gyrus, frontal medial orbital cortex, cingulate gyrus, and precuneus). Amyloid was not associated with reported sleep amount, symptoms of sleep-disordered breathing, trouble falling asleep, or Epworth Sleepiness Scale. Poor sleep may be a risk factor for AD and a potential early marker of AD or target for preventative interventions in midlife.

The Four-Factor Model of Depressive Symptoms in Dementia Caregivers : A Structural Equation Model of Ethnic Differences

Previous studies have suggested that 4 latent constructs (depressed affect, well-being, interpersonal problems, somatic symptoms) underlie the item responses on the Center for Epidemiological Studies Depression (CES-D) Scale. This instrument has been widely used in dementia caregiving research, but the fit of this multifactor model and the explanatory contributions of multifactor models have not been sufficiently examined for caregiving samples. The authors subjected CES-D data (N = 1,183) from the initial Resources for Enhancing Alzheimers Caregiver Health Study to confirmatory factor analysis methods and found that the 4-factor model provided excellent fit to the observed data. Invariance analyses suggested only minimal item-loading differences across race subgroups and supported the validity of race comparisons on the latent factors. Significant race differences were found on 3 of the 4 latent factors both before and after controlling for demographic covariates. African Americans reported less depressed affect and better well-being than White caregivers, who reported better well-being and fewer interpersonal problems than Hispanic caregivers. These findings clarify and extend previous studies of race differences in depression among diverse samples of dementia caregivers.

Visual attention and self-regulation of driving among older adults

BACKGROUND With the number of older drivers increasing, self-regulation of driving has been proposed as a viable means of balancing the autonomy of older adults against the sometimes competing demand of public safety. In this study, we investigate self-regulation of driving among a group of older adults with varying functional abilities. METHOD Participants in the study comprised 1,543 drivers aged 75 years or older. They completed an objective measure of visual attention from which crash risk was estimated, and self-report measures of driving avoidance, driving exposure, physical functioning, general health status, and vision. Crash records were obtained from the State Department of Public Safety. RESULTS Overall, participants were most likely to avoid driving in bad weather followed by driving at night, driving on high traffic roads, driving in unfamiliar areas, and making left-hand turns across oncoming traffic. With the exception of driving at night, drivers at higher risk of crashes generally reported greater avoidance of these driving situations than lower risk drivers. However, across all driving situations a significant proportion of higher risk drivers did not restrict their driving. In general, self-regulation of driving did not result in reduced social engagement. CONCLUSION Some older drivers with visual attention impairments do not restrict their driving in difficult situations. There is a need for physicians and family members to discuss driving behaviors with older adults routinely to ensure their safety. The association between visual attention and driving restriction also has implications for interventions aimed at preserving mobility in the elderly.