Sarah Tomaszewski Farias

Progression of Mild Cognitive Impairment to Dementia in Clinic- vs Community-Based Cohorts

BACKGROUND Mild cognitive impairment is increasingly recognized as an important public health problem associated with increased risk of developing dementia. Annual conversion rates, however, vary across different studies with clinic samples showing higher rates of conversion than community-based samples. OBJECTIVES To establish whether the rates of conversion from mild cognitive impairment to dementia differed according to recruitment source and, if so, to investigate factors that might explain this discrepancy. DESIGN Rates and predictors of conversion were examined in a prospective longitudinal study at a single center. SETTING Among the participants, 46% were recruited from a clinical setting and 54% were recruited directly through community outreach. PARTICIPANTS One hundred eleven individuals with mild cognitive impairment were followed up longitudinally for an average of 2.4 years (range, 0.5-4.0 years). MAIN OUTCOME MEASURES Conversion from mild cognitive impairment to dementia. RESULTS During the follow-up period, 28 individuals progressed to dementia with a mean (SD) time to conversion of 2.19 (0.72) years. The clinic sample had an annual conversion rate of 13%, whereas the community sample had an annual conversion rate of 3%. In a Cox proportional hazards model, clinic recruitment source alone was associated with an increased hazard of incident dementia (hazard ratio = 3.50; 95% confidence interval, 1.31-9.18; P = .01). When other variables were added to the model, only baseline functional impairment as measured by the Clinical Dementia Rating Scale (and no demographic, cognitive, or neuroimaging variables or mild cognitive impairment subtype) accounted for the differences in conversion rates across the 2 cohorts. CONCLUSIONS These findings add to the growing literature to suggest that the degree of functional impairment at baseline is an important predictor of conversion to dementia and may help explain differences in findings between epidemiological and clinic-based studies.

The Measurement of Everyday Cognition (ECog): Scale Development and Psychometric Properties

This article describes the development and validation of an instrument to assess cognitively mediated functional abilities in older adults, Everyday Cognition (ECog). The ECog is an informant-rated questionnaire comprised of multiple subscales. Confirmatory factor analysis (CFA) was used to examine its factor structure. Convergent validity was evaluated by comparing it to established measures of everyday function. External validity was evaluated by comparing ECog results across different clinical groups [cognitively normal, mild cognitive impairment (MCI), dementia]. CFA supported a seven-factor model including one global factor and six domain-specific factors (Everyday Memory, Language, Visuospatial Abilities, Planning, Organization, and Divided attention). The ECog correlated with established measures of functional status and global cognition, but only weakly with age and education. The clinical groups performed differently in each domain. In addition to the global factor, the Everyday Memory factor independently differentiated MCI from Normal, while the Everyday Language domain differentiated Dementia from MCI. Different subtypes of MCI also showed different patterns. Results suggest the ECog shows promise as a useful tool for the measurement of general and domain-specific everyday functions in the elderly.

Longitudinal Changes in Memory and Executive Functioning are Associated with Longitudinal Change in Instrumental Activities of Daily Living in older adults

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 relationship 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 5 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.

The relationship between neuropsychological performance and daily functioning in individuals with Alzheimer's disease: ecological validity of neuropsychological tests

The current study examined the relationship between neuropsychological test performance and functional status in 42 individuals diagnosed with Alzheimers disease. A comprehensive battery of cognitive tests was employed in order to assess a wide range of neuropsychological abilities. Functional status was measured through the use of both a performance-based scale of activities of daily living (an expanded version of the Direct Assessment of Functional Status; DAFS, Loewenstein et al., 1989), and by a caregiver/informant-based rating scale (Instrumental Activities of Daily Living; IADL, Lawton & Brody, 1969). Findings suggest that neuropsychological functioning is moderately predictive of functional status. Using multiple regression analyses, neuropsychological variables accounted for 25% of the variance in the IADL and 50% of the variance in the DAFS. Individual domains of both functional measures were also significantly predicted by the neuropsychological variables. The findings provide evidence of a relationship between neuropsychological test performance and ADLs in an Alzheimer disease patient population.

Cognitive and neuroimaging predictors of instrumental activities of daily living.

Impaired ability to conduct daily activities is a diagnostic criterion for dementia and a determinant of healthcare services utilization and caregiver burden. What predicts decline in instrumental activities of daily living (IADLs) is not well understood. This study examined measures of episodic memory, executive function, and MRI brain volumes in relation to baseline IADLs and as predictors of rate of IADL change. Participants were 124 elderly persons with cognitive function between normal and moderate dementia both with and without significant small vessel cerebrovascular disease. Random effects modeling showed that baseline memory and executive function (EXEC) were associated with baseline IADL scores, but only EXEC was independently associated with rate of change in IADLs. Whereas hippocampal and cortical gray matter volumes were significantly associated with baseline IADL scores, only hippocampal volume was associated with IADL change. In a model including cognitive and neuroimaging predictors, only EXEC independently predicted rate of decline in IADL scores. These findings indicate that greater executive dysfunction at initial assessment is associated with more rapid decline in IADLs. Perhaps executive function is particularly important with respect to maintaining IADLs. Alternatively, executive dysfunction may be a sentinel event indicating widespread cortical involvement and poor prognosis.

Video-EEG telemetry can be a crucial tool for neurologists experienced in epilepsy when diagnosing seizure disorders

We retrospectively reviewed the charts of 121 patients consecutively admitted to our epilepsy-monitoring unit (VET) during the period of 01 July 2001 to 31 December 2002. We excluded patients with a confirmed diagnosis of epilepsy who were admitted for invasive pre-surgical monitoring. Medical records were reviewed to collect demographic and clinical information that lead to the initial referral for VET by neurologists with expertise in epilepsy or by an epileptologist. We identified 29 patients (24%), whose diagnosis changed after VET. Their seizure duration ranged from 1 to 46 years. A diagnosis of epileptic seizures (ES) was made in four of the patients who were initially felt to have nonepileptic seizures (NES). The diagnosis of NES was made in 22 patients who were initially felt to have ES. All of these 29 patients had failed at least two or more antiepileptic drugs (AEDs). A misclassification of epilepsy syndrome was found in three patients. Eleven of the NES patients had risk factors that would increase the likelihood of ES, including significant head injury (n=6), febrile seizures (n=2), meningioencephalitis (n=2), and tumours (n=1). Four of these 11 patients had abnormal interictal EEGs. We conclude that VET is crucial in establishing a diagnosis in patients with seizures. Without VET, patients can be misclassified or receive ineffective treatment, even when being treated by specialists in epilepsy. Thus, VET, can help facilitate the most appropriate type of therapy in difficult to control patients.

Differences in Brain Volume, Hippocampal Volume, Cerebrovascular Risk Factors, and Apolipoprotein E4 Among Mild Cognitive Impairment Subtypes

OBJECTIVES To evaluate demographics, magnetic resonance imaging (MRI) measures, and vascular risk among mild cognitive impairment (MCI) subtypes. DESIGN Cross-sectional study. SETTING Both clinics and the community. PARTICIPANTS A total of 153 subjects with MCI, 218 cognitively normal older individuals (controls), and 68 patients with Alzheimer disease. MAIN OUTCOME MEASURES Classification of subjects with MCI according to current subtype diagnostic convention based on neuropsychological performance, estimates of vascular risk based on medical history, research MRI unless there was a specific contraindication, and apolipoprotein E genotype. RESULTS Of the 153 subjects with MCI, 65 were diagnosed with amnestic single-domain, 46 with amnestic multiple-domain, 27 with nonamnestic single-domain, and 15 with nonamnestic multiple-domain MCI. Analyses of control, MCI, and Alzheimer disease cases revealed significant differences in brain and hippocampal volumes between each group. Post hoc analyses of MRI measures among the MCI subtypes found that patients with amnestic single-domain MCI had significantly less brain atrophy and that hippocampal volume differed significantly from controls for the 2 amnestic forms of MCI. Apolipoprotein E genotype prevalence was significantly greater in the amnestic and nonamnestic subtypes of MCI. Conversely, the nonamnestic subtypes were more likely to have increased vascular risk and to be African American. CONCLUSIONS Amnestic forms of MCI appear to have demographic, genetic, and MRI findings suggestive of Alzheimer disease pathology, whereas the nonamnestic forms of MCI have findings suggestive of vascular disease. Importantly, however, all subjects with MCI showed evidence of brain injury, and the biological differences among subtypes are relatively subtle beyond the memory vs nonmemory groupings.

Psychogenic nonepileptic seizures: acute change in event frequency after presentation of the diagnosis.

Seizure frequency during inpatient video EEG monitoring was examined before and after the diagnosis of psychogenic nonepileptic seizures (PNES) was presented to patients (N=22). A control group of 10 patients with epileptic seizures (ES) were also followed from pre- to postdiagnosis. The number of PNES or ES within the 24-hour period prior to diagnosis was compared with the number of events that occurred within the 24-hour period after presentation of the diagnosis. Findings indicate that patients with PNES had a significant decrease in the frequency of events after diagnosis, while those with ES showed no change in event frequency after diagnosis. Eighteen of twenty-two patients with PNES had no further events during an acute follow-up period. Results suggest that providing patients with a diagnosis of PNES appears to reduce the acute frequency of PNES and may be an important first step in the long-term remediation of PNES. Long-term follow-up is needed to determine if such feedback alters the course of the disorder.

Heterogeneity of cognitive trajectories in diverse older persons.

This study examined trajectories of cognitive change in psychometrically matched measures of episodic memory, semantic memory, and executive function in an ethnically, demographically, and cognitively diverse sample of older persons. Individual rates of change showed considerable heterogeneity in each domain. Baseline clinical diagnosis predicted differential change in semantic memory and executive function, dementia > mild cognitive impairment (MCI) > normal, but average decline in verbal episodic memory was similar across all 3 diagnostic groups. There was substantial overlap of distributions of cognitive change across baseline diagnostic groups for all 3 measures. Cognitive change was strongly related to change in clinical diagnosis. Rapid and similar change was present for all 3 cognitive measures in patients with dementia and in those with normal cognition and those with MCI who progressed clinically. In cognitively normal patients, verbal episodic memory change was greater than change in the other two domains. Global status, measured by the Clinical Dementia Rating scale (Morris, 1993), predicted change in semantic memory and executive function, whereas APOE genotype predicted change in verbal episodic memory, and age had no effect on rates of change in any domain independent of global status and APOE. Results show important limitations in using cross-sectional diagnosis to predict prognosis and suggest that research to identify robust predictors of cognitive change across the full spectrum from normal to dementia is needed for better early identification of diseases that cause progressive decline.

Dementia in fragile X-associated tremor/ataxia syndrome (FXTAS): Comparison with Alzheimer's disease†

Neurocognitive deficits in fragile X‐associated tremor/ataxia syndrome (FXTAS) involve attentional control, working memory, executive functioning, and declarative and procedural learning. To date, no studies comparing FXTAS with other dementias have been done. We characterize the dementia in FXTAS, comparing it with Alzheimers disease. Retrospective chart review of 68 adults (50 men, 18 women) with FXTAS. 20 men with FXTAS dementia were matched by age, gender, and education to patients with mild Alzheimers dementia (AD). Neuropsychological measures were compared between the two groups: Boston Naming Test (BNT), phonemic fluency (Controlled Oral Word Association Test), digit span forward (DSF) and backward (DSB). Comparisons were based on analysis of covariance and t‐tests to assess significant differences between groups. 50% of men with FXTAS and no women were cognitively impaired. On mean scores of verbal fluency (22.83 in FXTAS vs. 28.83 in AD, P = 0.112), working memory (DSB, 4.80 in AD vs. 5.41 in FXTAS, P = 0.359), and language (BNT, 48.54 in AD vs. 54.20 in FXTAS, P = 0.089), there were no significant differences. Digit span forward, measuring attention, was significantly higher in subjects with FXTAS dementia (8.59, vs. 7.10 in AD, P = 0.010). Individuals with FXTAS have significant cognitive deficits, on the order of those in AD although the cognitive profiles in these dementias are not similar. Further research is needed to outline the neuropsychiatric profile in FXTAS and the correlation of genetic markers with the progression and severity of cognitive loss.