Anil K. Nair

Potential impact of amyloid imaging on diagnosis and intended management in patients with progressive cognitive decline.

Florbetapir F18 has been approved by the Food and Drug Administration for in vivo assessment of amyloid pathology in patients undergoing evaluation for Alzheimer disease (AD). The aim of this study was to determine the impact of amyloid imaging on the diagnoses and management of patients undergoing evaluation for cognitive decline. Patients were recruited to participate at 19 clinical sites. The site physician provided a provisional diagnosis, an estimate of their diagnostic confidence, and their plan for diagnostic evaluation and management both before and after receiving the results from amyloid imaging with florbetapir F18. Analyses compared the frequency of AD and non-AD diagnoses, plans for ancillary testing, and intended patient management before and after florbetapir imaging. A total of 229 patients participated in the trial (113 amyloid positive, 116 amyloid negative). After receiving the results of the florbetapir scan, diagnosis changed in 125/229, or 54.6% [95% confidence intervals (CI), 48.1%-60.9%], of cases, and diagnostic confidence increased by an average of 21.6% (95% CI, 18.3%-24.8%). A total of 199/229 or 86.9% (95% CI, 81.9%-90.7%) of cases had at least 1 change in their management plan. Intended cholinesterase inhibitor or memantine treatment increased by 17.7% (95% CI, 11.8%-25.8%) of all cases with positive scans and decreased by 23.3% (95% CI, 16.5%-31.8%) of all those with negative scans. Among subjects who had not yet undergone a completed work up, planned brain structural imaging (computed tomographic/magnetic resonance imaging) decreased by 24.4% (95% CI, 17.5%-32.8%) and planned neuropsychological testing decreased by 32.8% (95% CI, 25.0%-41.6%). In summary, amyloid imaging results altered physician’s diagnostic thinking, intended testing, and management of patients undergoing evaluation for cognitive decline.

Lower-Extremity Function in Cognitively Healthy Aging, Mild Cognitive Impairment, and Alzheimer's Disease

OBJECTIVE To examine differences in lower-extremity function in cognitive healthy older persons, older persons with mild cognitive impairment (MCI), and older persons with Alzheimers disease (AD). DESIGN Descriptive study. SETTING University Alzheimers disease clinical and research program. PARTICIPANTS Older persons (N=66) were studied (mean age, 76.7y); 22 were cognitively normal, 22 were diagnosed with probable MCI, 22 were diagnosed with probable AD. INTERVENTIONS Not applicable. MAIN OUTCOME MEASURES Lower-extremity function was assessed by the four-meter walk test (4MWT), Timed Up & Go (TUG) test, and sit-to-stand (STS) test. RESULTS Analysis of variance, adjusting for covariates, revealed that performance on the 4MWT was significantly lower in the MCI and AD groups as compared with controls. TUG test performance was worse in the AD group compared with controls. No significant group differences were found for STS performance. CONCLUSIONS These results suggest an association between cognitive impairment and lower-limb function in older persons. Walking speed could be evaluated for its possible utility in screening older persons at risk for cognitive impairment and falls.

Clock Drawing Test Ratings by Dementia Specialists: Interrater Reliability and Diagnostic Accuracy

The authors conducted a study of clock drawing test scoring by dementia specialists to determine interrater reliability and diagnostic accuracy. The authors randomly assigned 25 clocks from each of six predetermined groups based on consensus diagnosis (cognitive comparison subjects, subjects with a memory complaint but with normal neuropsychological testing, subjects with probable and possible mild cognitive impairment, and subjects with possible and probable Alzheimers disease) to dementia specialists for blinded scoring using a binary yes/no impairment system and a 0-10 scale as subjectively determined by each individual clinician rater. The authors collapsed the six groups into three (comparison subjects, mild cognitive impairment patients, and Alzheimers disease patients) and analyzed interrater reliability, sensitivity, and specificity for consensus diagnosis of mild cognitive impairment and Alzheimers disease. The authors found excellent interrater reliability, sensitivity, and specificity for predicting consensus diagnosis. The 0-10 clock drawing test rating scale was more predictive of consensus diagnosis than the binary impairment scale. Based on rating systems, clock drawing test scoring by dementia clinicians had excellent interrater reliability and sensitivity for differentiating the mild Alzheimers disease subjects from comparison subjects.

Diagnostic utility of the NAB List Learning test in Alzheimer's disease and amnestic mild cognitive impairment.

Measures of episodic memory are often used to identify Alzheimers disease (AD) and mild cognitive impairment (MCI). The Neuropsychological Assessment Battery (NAB) List Learning test is a promising tool for the memory assessment of older adults due to its simplicity of administration, good psychometric properties, equivalent forms, and extensive normative data. This study examined the diagnostic utility of the NAB List Learning test for differentiating cognitively healthy, MCI, and AD groups. One hundred fifty-three participants (age: range, 57-94 years; M = 74 years; SD, 8 years; sex: 61% women) were diagnosed by a multidisciplinary consensus team as cognitively normal, amnestic MCI (aMCI; single and multiple domain), or AD, independent of NAB List Learning performance. In univariate analyses, receiver operating characteristics curve analyses were conducted for four demographically-corrected NAB List Learning variables. Additionally, multivariate ordinal logistic regression and fivefold cross-validation was used to create and validate a predictive model based on demographic variables and NAB List Learning test raw scores. At optimal cutoff scores, univariate sensitivity values ranged from .58 to .92 and univariate specificity values ranged from .52 to .97. Multivariate ordinal regression produced a model that classified individuals with 80% accuracy and good predictive power. (JINS, 2009, 15, 121-129.).

A New Scale Measuring Psychologic Impact of Genetic Susceptibility Testing for Alzheimer Disease

This paper describes the development and psychometric properties of a new scale for assessing the psychologic impact of genetic susceptibility testing for Alzheimer disease (AD). The new instrument, The REVEAL Impact of Genetic Testing for Alzheimers disease (IGT-AD) was designed to examine the unique nature of genetic information and the disease course of AD. The scale was tested as a part of a multicenter clinical trial designed to evaluate the impact of AD risk assessment and data were collected from 276 participants in the study. Using an iterative process of principal component analysis and Cronbach α, the final 16-item IGT-AD was found to have a 2-factor structure with excellent internal reliability. Construct validity was established by patterns of correlation with other standardized self-reported measures. This scale should be useful in the identification of patients who maybe susceptible to the negative effects of receiving genetic information, monitoring of patients who have received genetic information, and as a tool for researchers who wish to study the effects of genetic susceptibility testing for AD.

Predicting cognitive decline and conversion to Alzheimer's disease in older adults using the NAB List Learning test

To validate the Neuropsychological Assessment Battery (NAB) List Learning test as a predictor of future multi-domain cognitive decline and conversion to Alzheimers disease (AD), participants from a longitudinal research registry at a national AD Center were, at baseline, assigned to one of three groups (control, mild cognitive impairment [MCI], or AD), based solely on a diagnostic algorithm for the NAB List Learning test (Gavett et al., 2009), and followed for 1-3 years. Rate of change on common neuropsychological tests and time to convert to a consensus diagnosis of AD were evaluated to test the hypothesis that these outcomes would differ between groups (AD>MCI>control). Hypotheses were tested using linear regression models (n = 251) and Cox proportional hazards models (n = 265). The AD group declined significantly more rapidly than controls on Mini-Mental Status Examination (MMSE), animal fluency, and Digit Symbol; and more rapidly than the MCI group on MMSE and Hooper Visual Organization Test. The MCI group declined more rapidly than controls on animal fluency and CERAD Trial 3. The MCI and AD groups had significantly shorter time to conversion to a consensus diagnosis of AD than controls. The predictive validity of the NAB List Learning algorithm makes it a clinically useful tool for the assessment of older adults.

Isolated Unilateral Hypoglossal Nerve Palsy Due to Vertebral Artery Dissection

We report the case of a patient with unilateral tongue weakness secondary to an isolated lower motor neuron hypoglossal nerve palsy that was caused by a right vertebral artery dissection in the lower neck. The patient had a boggy tongue with a deviation to the right side but an otherwise normal neurological examination. Magnetic resonance angiography showed a narrow lumen of the right vertebral artery in the neck. After initially treating the patient with aspirin in the emergency room and later with warfarin for three months, there was complete recanalization of the right vertebral artery. Only one other case of vertebral artery dissection and twelfth nerve palsy has been reported before.

Comparative Analysis of State Driving Laws on Crash Rates of Older Drivers in all 50 U.S. States

Pearson chi-square = 5.08, P = .03). After performing univariate analyses on all predictor variables, a multivariate model was constructed including race, number of medical diagnoses, diagnosis of dementia, and HCA that demonstrated that longer time of enrollment in PACE was independently associated with change in code status toward less-aggressive care (P = .048). Regarding other secondary outcomes, 88% of participants received care consistent with their code status at TOD, 2% had their code status changed by family members or while receiving emergency medical services and hospitalized, and 5% were hospitalized although they had requested DNH. For 4% of participants, records from outside hospitals could not be obtained. Overall, participants were hospitalized only 7.1 ± 13.6 days during the last 6 months of life, and 63% of participants died in a nonhospital setting. These data suggest that longer exposure to the IDT results in less-aggressive code status at time of death. This trend toward less-aggressive care and the statistically significant association with ongoing code status discussions has not been well described previously. Because these code status discussions commenced at enrollment and were addressed regularly, it is likely that these individuals had more time to weave their knowledge of options and their preferences into a plan that could be shared with community members and be followed. In comparison, a 25% rate of discussion regarding end of life and resuscitation was described to occur in a study population of ill older adults. Efforts to elicit and document patient preferences and HCA designation possibly resulted in the death of the participants in the current study having better alignment with their preferences. In summary, focused commitment to regular discussions and documentation of advance care planning and endof-life care implementation by the PACE interdisciplinary team can serve as a model for positive outcomes in end-oflife geriatric care.

Elderly driving laws and associated crash risk: Analysis of state level data in the USA

Background: There are currently 31 million licensed drivers (or 15% of all licensed drivers) over the age of 65. This number is expected to grow rapidly as the elderly population is predicted to double by 2030. With this impending increase of elderly drivers and their higher susceptibility to physical and mental deterioration, it is important to consider their safety as well as the safety of others on the road. State laws vary significantly as to elderly license renewal periods and renewal requirements, which could be particularly important in assessing elderly drivers’ continued ability to drive. We looked at the duration of license renewal in several states and compared elderly driver crash statistics among states with short and long renewal periods.Methods: 2009 accident data from the NHTSAwas collected and sorted with respect to age and state. Total population estimates, again sorted by age and state, were also collected from the US Census Bureau. The data sets were then compiled to create elderly accident ratios by state and compared to data on license renewal duration (RD). By performing t-tests on data stratified by different RDs, the relationship between state licensing periods and elderly driving characteristics was assessed. Results: When comparing RD to crash rates, only a renewal period of 2 years is associated with lower crash rates (p1⁄4 0.028) among the elderly. The crash rates for these states vary from 55 to 177 crashes per million elderly drivers. The five safest states for elderly drivers (DC, HI,MA, CT, andNY) have variable RDs (2-8 years). The worst 5 states for elderly drivers involved in crashes (MS, AK, MT, KY, and ND) all havemedian license RDs of 4 to 5 years.Conclusions: Frequent renewal (2 years) is associated with a reduction in elderly crashes in our analysis using state level data. However, some of the safest elderly driving states are MA and NY, with 5and 8-year renewal durations respectively. A license renewal period of more than 2 years does not seem to be a efficient predictor of elderly driving crash rates when looking at all 50 states.