Abnormality of gait as a predictor of non-Alzheimer's dementia.

BACKGROUND: Neurologic abnormalities affecting gait occur early in several types of non-Alzheimer's dementias, but their value in predicting the development of dementia is uncertain. METHODS: We analyzed the relation between neurologic gait status at base line and the development of dementia in a prospective study involving 422 subjects older than 75 years of age who lived in the community and did not have dementia at base line. Cox proportional-hazards regression analysis was used to calculate hazard ratios with adjustment for potential confounding demographic, medical, and cognitive variables. RESULTS: At enrollment, 85 subjects had neurologic gait abnormalities of the following types: unsteady gait (in 31 subjects), frontal gait (in 12 subjects), hemiparetic gait (in 11 subjects), neuropathic gait (in 11 subjects), ataxic gait (in 10 subjects), parkinsonian gait (in 8 subjects), and spastic gait (in 2 subjects). During follow-up (median duration, 6.6 years), there were 125 newly diagnosed cases of dementia, 70 of them cases of Alzheimer's disease and 55 cases of non-Alzheimer's dementia (47 of which involved vascular dementia and 8 of which involved other types of dementia). Subjects with neurologic gait abnormalities had a greater risk of development of dementia (hazard ratio, 1.96 [95 percent confidence interval, 1.30 to 2.96]). These subjects had an increased risk of non-Alzheimer's dementia (hazard ratio, 3.51 [95 percent confidence interval, 1.98 to 6.24]), but not of Alzheimer's dementia (hazard ratio, 1.07 [95 percent confidence interval, 0.57 to 2.02]). Of non-Alzheimer's dementias, abnormal gait predicted the development of vascular dementia (hazard ratio, 3.46 [95 percent confidence interval, 1.86 to 6.42]). Among the types of abnormal gait, unsteady gait predicted vascular dementia (hazard ratio, 2.61), as did frontal gait (hazard ratio, 4.32) and hemiparetic gait (hazard ratio, 13.13). CONCLUSIONS: The presence of neurologic gait abnormalities in elderly persons without dementia at base line is a significant predictor of the risk of development of dementia, especially non-Alzheimer's dementia.

Leisure activities and the risk of dementia in the elderly.

BACKGROUND: Participation in leisure activities has been associated with a lower risk of dementia. It is unclear whether increased participation in leisure activities lowers the risk of dementia or participation in leisure activities declines during the preclinical phase of dementia. METHODS: We examined the relation between leisure activities and the risk of dementia in a prospective cohort of 469 subjects older than 75 years of age who resided in the community and did not have dementia at base line. We examined the frequency of participation in leisure activities at enrollment and derived cognitive-activity and physical-activity scales in which the units of measure were activity-days per week. Cox proportional-hazards analysis was used to evaluate the risk of dementia according to the base-line level of participation in leisure activities, with adjustment for age, sex, educational level, presence or absence of chronic medical illnesses, and base-line cognitive status. RESULTS: Over a median follow-up period of 5.1 years, dementia developed in 124 subjects (Alzheimer's disease in 61 subjects, vascular dementia in 30, mixed dementia in 25, and other types of dementia in 8). Among leisure activities, reading, playing board games, playing musical instruments, and dancing were associated with a reduced risk of dementia. A one-point increment in the cognitive-activity score was significantly associated with a reduced risk of dementia (hazard ratio, 0.93 [95 percent confidence interval, 0.90 to 0.97]), but a one-point increment in the physical-activity score was not (hazard ratio, 1.00). The association with the cognitive-activity score persisted after the exclusion of the subjects with possible preclinical dementia at base line. Results were similar for Alzheimer's disease and vascular dementia. In linear mixed models, increased participation in cognitive activities at base line was associated with reduced rates of decline in memory. CONCLUSIONS: Participation in leisure activities is associated with a reduced risk of dementia, even after adjustment for base-line cognitive status and after the exclusion of subjects with possible preclinical dementia. Controlled trials are needed to assess the protective effect of cognitive leisure activities on the risk of dementia.

Decreased neprilysin immunoreactivity in Alzheimer disease, but not in pathological aging.

Although evidence suggests that extensive cortical beta-amyloid (Abeta) deposition is essential in Alzheimer disease (AD), it is also detected in nondemented elderly individuals with pathologic aging (PA). Given evidence that neutral endopeptidase (NEP) or neprilysin, a key enzyme for clearance of Abeta, is decreased in AD, the goal of the present study was to determine if NEP was also decreased in PA. We measured NEP immunoreactivity in frontal cortex of 12 AD and six PA cases and compared this with 10 normal (N) elderly individuals. None had any significant other pathology, and they were similar with respect to age, sex, and postmortem delay. In addition, Abeta1-40 and Abeta1-42 were measured by enzyme-linked immunosorbent assay (ELISA), whereas tau, synaptophysin, and alpha-synuclein were measured on Western blots. The AD cases had more neuritic plaques, neurofibrillary tangles, higher Braak stage, and more tau immunoreactivity in frontal cortex than both PA and N. In contrast, both PA and AD had more senile plaques and Abeta1-42 than N. NEP immunoreactivity was decreased in AD but not in PA. The decrease was unlikely the result of neuronal or synaptic loss because NEP immunoreactivity in frontotemporal degeneration with comparable degrees of synaptic loss as the AD cases was not different from control subjects. Although NEP enzyme activity was decreased in approximately half the AD cases, on average, it was not decreased compared with N or PA. The results add further evidence that PA is distinct from AD and indicate that decreased Abeta degradation by NEP is unlikely to contribute significantly to amyloid deposition in PA or, in many cases, of AD.

Screening for Alzheimer's disease: the memory impairment screen versus the conventional three-word memory test.

OBJECTIVES: To improve screening for Alzheimer's disease (AD) with the Memory Impairment Screen (MIS), a 4-minute, four-item delayed free and cued recall memory test with controlled learning and high discriminative validity. To assess the discriminative validity of the MIS for AD and to compare it with the conventional three-word memory test, a delayed free recall task, widely recommended as a dementia-screening test in clinical practice. DESIGN: Cross-sectional validation study nested within a longitudinal study of aging and dementia. The MIS and the standard three-word memory task were administered as part of a comprehensive neurological and neuropsychological evaluation. SETTING: Einstein Aging Study at the Albert Einstein College of Medicine, Bronx, New York. PARTICIPANTS: Two hundred forty community-dwelling older adults. MEASUREMENTS: Sensitivity, specificity, and positive predictive value (PPV) were calculated for the MIS and three-word memory test as screening tests for AD. RESULTS: In comparison with the three-word memory task, the MIS had higher sensitivity (.86 vs.65), higher specificity (.97 vs.85), and greater PPV (.80 vs.37) as a screen for AD. CONCLUSIONS: The MIS had high discriminative validity as a screening test for AD and substantially outperformed the three-word memory task. Given its validity and brevity, the MIS has important advantages as an AD screen for use in primary care.

Validity of divided attention tasks in predicting falls in older individuals: a preliminary study.

OBJECTIVES: Although cognitive impairment is known to be a major risk factor for falls in older individuals, the role of cognitive tests in predicting falls has not been established. Limited attentional resources may increase the risk for falls in older individuals. We examined the reliability and validity of divided attention tasks, walking while talking (WWT), in predicting falls. DESIGN: A prospective cohort study of 12-months' duration. SETTING: Community-based longitudinal aging study, the Einstein Aging Study. PARTICIPANTS: Sixty nondemented community-living subjects, aged 65 to 98 (mean age +/- standard deviation = 79.6 +/- 6.3). MEASUREMENTS: Simple and complex versions of the WWT task in addition to standard balance and cognitive assessments. The primary outcome was cumulative incidence of falls at 12 months. RESULTS: Thirteen subjects fell over the 12 months, four of whom had major injuries. The WWT task had good interrater reliability (r = 0.602, P <.001). Poor performance on simple (odds ratio (OR) = 7.02, 95% confidence interval (CI) = 1.7-29.4) and complex WWT tasks (OR = 13.7, 95% CI = 2.3-83.6) was highly predictive of falls. The simple task had a sensitivity of 46% and specificity of 89%. For the complex task, sensitivity was 39%, and specificity was 96%. CONCLUSIONS: The WWT is a reliable and valid test to identify older individuals at high risk for falls. Future studies with larger sample sizes and in different settings are needed to confirm the findings of this study.

Screening for dementia by telephone using the memory impairment screen.

OBJECTIVES: : To develop and assess telephone-based screening tests for dementia, especially Alzheimer's disease (AD). DESIGN: : A cross-sectional validation study nested within a longitudinal study of aging and dementia. SETTING: : The Einstein Aging Study of the Albert Einstein College of Medicine, Bronx, New York. PARTICIPANTS: : Three hundred elderly community volunteers living in Bronx County, 27 of whom were diagnosed with dementia based on in-person clinical evaluation. Of the 27 individuals with dementia, 18 had AD. MEASUREMENTS: : A telephone battery was administered that included the Memory Impairment Screen by telephone (MIS-T, a test of semantic memory), the Category Fluency Test (CF-T), and the Telephone Instrument for Cognitive Status (TICS). An in-person evaluation then followed that included a neurological examination, a neuropsychological battery, demographics, and medical history. RESULTS: : The telephone battery was well accepted. The MIS-T required 4 minutes; the CF-T, 3 minutes; and the TICS, 10 minutes. The MIS-T had excellent sensitivity and specificity when compared with the CF-T and the TICS. Using cutscores on all three tests that provide a sensitivity of 78%, specificity was significantly higher for the MIS-T (93%) than for the CF-T (78%, P<.05) or the TICS (80%, P<.05). Combining the MIS-T and CF-T improved discriminative validity but increased screening time and the complexity of scoring. Normative data for the MIS-T, the CF-T, and the TICS for use in settings with different base rates (prevalence) of dementia are presented in this study. CONCLUSION: : The MIS-T outperforms the CF-T and the TICS as a valid and time-efficient telephone screen for dementia. For applications that require optimal efficiency and accuracy, the MIS-T is recommended.

The effects of Alzheimer's disease on item output in verbal fluency tasks.

We collected category fluency data from several moderate-to-large samples of participants at three different sites: the New York University Aging and Dementia Center, the Oregon Health Services Aging and Dementia Research Center, and the Einstein Aging Study at the Albert Einstein College of Medicine. These data were analyzed by calculating the average relative frequency (e.g., typicality) of the category members generated by each participant. Alzheimer's disease (AD) patients recalled fewer atypical members of common taxonomic categories than did the elderly control group. In addition, the probability of producing an item declined at a greater rate for AD patients than for the elderly control group over the duration of the task. According to sequential sampling models, this latter result implies that the rate at which AD patients search memory must be slower than the search rate of the elderly controls.

Detecting dementia with the Hopkins Verbal Learning Test and the Mini-Mental State Examination.

The Hopkins Verbal Learning Test (HVLT) and the Mini-Mental State Examination (MMSE) were administered to 323 non-demented elderly and 70 individuals who meet DSM-IV criteria for dementia in order to compare the validity of these two measures for detecting mild dementia and for the two most common dementia subtypes, Alzheimer's disease (AD) and vascular dementia (VaD). The study was conducted in an elderly, ethnically diverse community-dwelling population. Sensitivity, specificity, positive and negative predictive values were calculated over a range of clinically relevant cut scores for each test. We analyzed the influence of age, education, reading ability and sex on test performance using logistic regression models. When sensitivity is held constant at 0.69, the specificity for the HVLT total recall was 0.89 and the MMSE 0.82 for all dementias (P=.10). Age, sex and education did not significantly influence test performance for either test in this sample. Results were similar for AD and VaD. However, while adding a measure of reading ability to the regression models did not affect the overall dementia model, it resulted in improved specificities when combined with the MMSE for AD and combined with the HVLT for VaD. Additional tests such as reading ability can improve discrimination of dementia subtypes. The modest sensitivity of either the HVLT or the MMSE alone suggests that further neuropsychological evaluation is required to confirm dementia diagnosis.

Category size effects in semantic and letter fluency in Alzheimer's patients.

Many studies have found that patients with Alzheimer's disease (AD) perform significantly worse than normal controls on verbal fluency tasks. Moreover, some studies have found that AD patients' deficits compared to controls are more severe for semantic fluency (e.g., vegetables) than for letter fluency (e.g. words that begin with F). These studies, however, have not taken category size into account. A comparison of AD patients and age-matched controls on three semantic and three letter categories revealed that both the size and type of a category significantly predicted AD patients' deficits on verbal fluency tasks. These results suggest that the verbal fluency of AD patients will be most attenuated on large semantic categories.

Walking while talking: effect of task prioritization in the elderly.

OBJECTIVE: To examine the effect of 2 instructions on the same walking while talking (WWT) task on task prioritization by nondisabled subjects. DESIGN: Cross-sectional survey with within subject comparisons. SETTING: Community-based sample. PARTICIPANTS: Older adults (N=189; mean age, 80.2+/-4.9y), who did not meet criteria from the Diagnostic and Statistical Manual, Fourth Edition, for dementia and were able to independently perform activities of daily living. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Verbal and gait measures on the same WWT task with 2 different instructions: paying attention to both talking and walking (WWT-C) and paying attention only to talking (WWT-T). RESULTS: Task prioritization effects were seen on walking but not on talking. Compared with their baseline normal walking velocity (without talking), subjects slowed down more on WWT-T (median change, 28.3%) than WWT-C (median change, 26.4%). Comparing the 2 WWT conditions, velocity and cadence was slower during WWT-T compared with WWT-C, with longer stride length. Verbal output was not significantly different on the 2 conditions. CONCLUSIONS: Changing instructions while maintaining the same cognitive and motor tasks on WWT in older adults result in task prioritization effects.

Retention weighted recall improves discrimination of Alzheimer's disease.

Impaired recall for early items (primacy) and late items (recency) on word list recall tests are seen in Alzheimer's disease (AD). We compared conventional scoring on the Telephone Instrument for Cognitive Status (TICS) recall list with scorings based on retention-weighted recall (RWR: each item weighted by its serial position) in older adults participating in a community-based aging study. Subjects with mild AD (N=18) did not differ from those without dementia (N=231) with respect to recency (46% vs. 59%, p = 0.2), but had impaired primacy (2% vs. 39%, p < .001) on word recall on the TICS. RWR scoring improved the effect size (1.52 SD) compared to conventional scoring (1.08 SD). With a fixed sensitivity of 85%, specificity was lower using conventional scoring (56%) than RWR (76%) scoring. Our findings suggest that optimized RWR scoring of word list free recall can improve detection of mild AD compared to conventional scoring.

Doctoral clinical geropsychology training in a primary care setting.

Most older adults diagnosed with a mental disorder receive treatment in primary care settings that lack personnel skilled in geropsychological diagnosis and treatment. The Ferkauf Older Adult Program of Yeshiva University endeavors to bridge this gap by providing training in geriatric psychology, through coursework and diverse clinical practica, to clinical psychology doctoral students within a large urban professional psychology program. In an innovative effort to provide the most disadvantaged elderly with comprehensive mental health treatment and maximize trainee exposure to an interdisciplinary treatment model, the program also pairs selected doctoral psychology trainees with medical residents to optimize integrated mental health service delivery for primary care elderly. The program has the following core objectives: (1) Infuse the mental health and aging knowledge base into the regular graduate curriculum; (2) Provide interdisciplinary training in geropsychological diagnostic and consultative services within an urban primary care setting; (3) Provide interdisciplinary training in the practice of psychological and neuropsychological evaluation of elderly; (4) Provide training in geropsychological psychotherapeutic intervention, including individual, couples/family, and brief/psycho-educational therapies with outpatient older adults. These objectives are achieved by pooling the resources of a graduate school of psychology, a local public hospital, and an academic medical center to achieve educational and clinical service goals.