Faculty Bibliography

Idiopathic normal pressure hydrocephalus (iNPH) is the most common cause of hydrocephalus in adults. The diagnosis may be challenging, requiring collaborative efforts between different specialists. According to the International Society for Hydrocephalus and Cerebrospinal Fluid Disorders, iNPH should be considered in the differential of any unexplained gait failure with insidious onset. Recognizing iNPH can be even more difficult in the presence of comorbid neurologic disorders. Among these, idiopathic Parkinson's disease (PD) is one of the major neurologic causes of gait dysfunction in the elderly. Both conditions have their peak prevalence between the 6th and the 7th decade. Importantly, postural instability and gait dysfunction are core clinical features in both iNPH and PD. Therefore, diagnosing iNPH where diagnostic criteria of PD have been met represents an additional clinical challenge. Here, we report a patient with parkinsonism initially consistent with PD who subsequently displayed rapidly progressive postural instability and gait dysfunction leading to the diagnosis of concomitant iNPH. In the following sections, we will review the clinical features of iNPH, as well as the overlapping and discriminating features when degenerative parkinsonism is in the differential diagnosis. Understanding and recognizing the potential for concomitant disease are critical when treating both conditions.

Purpose To assess the diagnostic performance of the callosal angle (CA) and Evans index (EI) measures and to determine their role versus automated volumetric methods in clinical radiology. Materials and Methods Magnetic resonance (MR) examinations performed before surgery (within 1-5 months of the MR examination) in 36 shunt-responsive patients with normal-pressure hydrocephalus (NPH; mean age, 75 years; age range, 58-87 years; 26 men, 10 women) and MR examinations of age- and sex-matched patients with Alzheimer disease (n = 34) and healthy control volunteers (n = 36) were studied. Three blinded observers independently measured EI and CA for each patient. Volumetric segmentation of global gray matter, white matter, ventricles, and hippocampi was performed by using software. These measures were tested by using multivariable logistic regression models to determine which combination of metrics is most accurate in diagnosis. Results The model that used CA and EI demonstrated 89.6%-93.4% accuracy and average area under the curve of 0.96 in differentiating patients with NPH from patients without NPH (ie, Alzheimer disease and healthy control). The regression model that used volumetric predictors of gray matter and white matter was 94.3% accurate. Conclusion CA and EI may serve as a screening tool to help the radiologist differentiate patients with NPH from patients without NPH, which would allow for designation of patients for further volumetric assessment. (c) RSNA, 2017.

BACKGROUND AND PURPOSE: There is limited evidence to support the use of high-volume lumbar taps over lower-volume taps in the diagnosis of normal pressure hydrocephalus. The purpose of this study is to detect whether the volume of CSF removed from patients undergoing high-volume diagnostic lumbar tap test for normal pressure hydrocephalus is significantly associated with post-lumbar tap gait performance. MATERIALS AND METHODS: This retrospective study included 249 consecutive patients who underwent evaluation for normal pressure hydrocephalus. The patients were analyzed both in their entirety and as subgroups that showed robust response to the lumbar tap test. The volume of CSF removed was treated as both a continuous variable and a discrete variable. Statistical tests were repeated with log-normalized volumes. RESULTS: This study found no evidence of a relationship between the volume of CSF removed during the lumbar tap test and subsequent gait test performance in the patient population (Pearson coefficient r = 0.049-0.129). Log normalization of the volume of CSF removed and controlling for age and sex failed to yield a significant relationship. Subgroup analyses focusing on patients who showed greater than 20% improvement in any of the gait end points or who were deemed sufficiently responsive clinically to warrant surgery also yielded no significant relationships between the volume of CSF removed and gait outcomes, but there were preliminary findings that patients who underwent tap with larger-gauge needles had better postprocedure ambulation among patients who showed greater than 20% improvement in immediate time score (P = .04, n = 62). CONCLUSIONS: We found no evidence to support that a higher volume of CSF removal impacts gait testing, suggesting that a high volume of CSF removal may not be necessary in a diagnostic lumbar tap test.

BACKGROUND/AIMS: The aim was to examine added benefits of a Comprehensive, Individualized, Person-Centered Management (CI-PCM) program to memantine treatment. METHODS: This was a 28-week, clinician-blinded, randomized, controlled, parallel-group study, with a similar study population, similar eligibility criteria, and a similar design to the memantine pivotal trial of Reisberg et al. [N Engl J Med 2003;348:1333-1341]. Twenty eligible community-residing Alzheimer disease (AD) subject-caregiver dyads were randomized to the CI-PCM program (n = 10) or to usual community care (n = 10). Primary outcomes were the New York University Clinician's Interview-Based Impression of Change Plus Caregiver Input (NYU-CIBIC-Plus), assessed by one clinician set, and an activities of daily living inventory, assessed by a separate clinician set at baseline and at weeks 4, 12, and 28. RESULTS: Primary outcomes showed significant benefits of the CI-PCM program at all post-baseline evaluations. Improvement on the NYU-CIBIC-Plus in the management group at 28 weeks was 2.9 points over the comparator group. The memantine 2003 trial showed an improvement of 0.3 points on this global measure in memantine-treated versus placebo-randomized subjects at 28 weeks. Hence, globally, the management program intervention benefits were 967% greater than memantine treatment alone. CONCLUSION: These results are approximately 10 times those usually observed with both nonpharmacological and pharmacological treatments and indicate substantial benefits with the management program for advanced AD persons.

BACKGROUND: Neuropsychological and depression measures have been found to predict cognitive functioning. We compared these associations among whites and Spanish-speaking Hispanics. METHODS: Fifty-two pairs of whites and Hispanics were matched demographically and clinically in a cross-sectional study. Hierarchical regression analyses predicted Global Deterioration Scale (GDS) rating by baseline neuropsychological tests and depression symptoms. RESULTS: Neuropsychological tests predicted GDS better in whites; depression symptoms-specifically retardation-predicted well in Hispanics but not whites. Immediate recall of the New York University (NYU)-Paragraph Test and the Retardation item of the Hamilton Depression Rating Scale were associated with GDS in Hispanics and delayed recall of the NYU-Paragraph Test and Wechsler Adult Intelligence Scale-Digit Symbol in whites. Neuropsychological tests and depression symptoms predicted GDS differently in Hispanics and whites. DISCUSSION: These results suggest that other measures should be considered to increase the predictive accuracy of neuropsychological tests when assessing cognitive status in Spanish-speaking Hispanics. Additional studies of specific ethnic/racial and sociodemographic subgroups are warranted.

Evidence suggests that normal pressure hydrocephalus (NPH) is underdiagnosed in day to day radiologic practice, and differentiating NPH from cerebral atrophy due to other neurodegenerative diseases and normal aging remains a challenge. To better characterize NPH, we test the hypothesis that a prediction model based on automated MRI brain tissue segmentation can help differentiate shunt-responsive NPH patients from cerebral atrophy due to Alzheimer disease (AD) and normal aging. Brain segmentation into gray and white matter (GM, WM), and intracranial cerebrospinal fluid was derived from pre-shunt T1-weighted MRI of 15 shunt-responsive NPH patients (9 men, 72.6 +/- 8.0 years-old), 17 AD patients (10 men, 72.1 +/- 11.0 years-old) chosen as a representative of cerebral atrophy in this age group; and 18 matched healthy elderly controls (HC, 7 men, 69.7 +/- 7.0 years old). A multinomial prediction model was generated based on brain tissue volume distributions. GM decrease of 33 % relative to HC characterized AD (P < 0.005). High preoperative ventricular and near normal GM volumes characterized NPH. A multinomial regression model based on gender, GM and ventricular volume had 96.3 % accuracy differentiating NPH from AD and HC. In conclusion, automated MRI brain tissue segmentation differentiates shunt-responsive NPH with high accuracy from atrophy due to AD and normal aging. This method may improve diagnosis of NPH and improve our ability to distinguish normal from pathologic aging.

Background: A decade ago, the senior author and colleagues published a multicenter study which demonstrated the efficacy of memantine in the treatment of moderate to severe Alzheimer's disease (AD) (Reisberg, et al, N Engl J Med., 2003). This study served as a pivotal trial which supported the US and EU approvals of memantine as the first treatment for advanced AD. The advent of pharmacologic treatment of advanced AD served to highlight the continuing needs of these persons. Therefore, we simulta- neously developed a science of AD management (Reisberg, et al, Int Psychogeriatr, 1999; Reisberg, et al, Am J Alzheimers Dis Other Demen, 2002). After the U.S. approval of memantine treatment we embarked upon a study comparing a Comprehensive, Individualized, Person Centered Management Program (CI-PCM) in persons receiving memantine treatment, with memantine treatment alone. The inclusion criteria, outcome measures and study design were based on our 2003 NEJM memantine study. Subjects were randomized to CIPCM plus memantine treatment (n=10), or memantine treatment alone (controls, n=10). A primary pivotal, outcome measure was the NYU CIBIC-Plus, a global primary outcome used in the 2003 pivotal memantine trial. We recently reported that the CI-PCM+memantine treatment subjects showed significant improvement over the controls on this global outcome measure at all time periods examined (ie, 4, 12 and 28 weeks, p<0.01) (Reisberg, et al, Alzheimer's & Dementia, in press). Herein we describe the source and the meaning of the observed differences. Methods: The NYU CIBIC-Plus (Clinician's Interview Based Impression of Change, Plus Caregiver Input) assessment is comprised of 2 parts: Part 1. A subject interview, and Part 2: A caregiver interview. Part 1 has a cognitive component, a behavioral component total score, and a behavioral global score. Part 2 has a functional disability stage, a behavioral component total score, and a behavioral global score. Differences between the CI-PCM treatment group and the con!

Background: Demonstration of efficacy of memantine treatment for persons with moderate to severe Alzheimer's disease (AD) over 28 weeks (Reisberg, et al., N. Engl. J. Med., 2003) highlighted both treatment possibilities and treatment needs of persons with advanced AD. In prior work, we developed a science of AD management (Reisberg, et al., Am. J. Alzheimers Dis., 2002), based upon scientific observations of the retrogenesis process and other pathologic AD processes (Reisberg, et al., Eur. Arch. Psych. Clin. Neurosci., 1999; Souren, et al., J. Am. Geriatr. Soc., 1995; Franssen, et al., Arch Neurol., 1993). Herein, we investigated the hypothesis that application of this AD management science would result in improved outcomes beyond those with pharmacologic treatment alone. Methods: The same subject selection procedures were applied as in our published, double-blind, memantine trial. These included: community residence, age > 50, probable AD, a Global Deterioration Scale stage of 5 or 6, a Functional Assessment Staging (FAST) level of > 6a, and an MMSE score of 3 to 14. All subjects were titrated to a maintenance dose of memantine, 10 mg bid, as tolerated. Twenty participants were randomized to one of two groups, each comprised of 10 subjects. The intervention group received the CI-PCM program; the control group received financial compensation upon completion of study landmarks. Results: The first results of this study, presented herein, examined the primary outcome measure, the Clinician's Interview-Based Impression of Change Plus Caregiver Input (CIBIC-Plus) global scores (New York University version) (Reisberg,Int. Psychogeriatr., 2007). This assessment comprehensively evaluates change in terms of cognition, function and behavior. The results indicated significant improvement in CIBIC-Plus scores in the subjects in the management program versus the subjects receiving financial compensation (p < 0.01 at weeks 4 and 12 and p < 0.001 at week 28), with enhanced benefits throughout the 28 week stud!

This study examines whether behavioral measures obtained in nondemented elderly can predict cognitive status at 2-year follow-up. Prior studies have established that delayed paragraph recall can help predict short-term risk for decline to mild cognitive impairment and Alzheimer disease. It was examined whether prediction accuracy can be improved by adding a discrimination-and-generalization task that has previously been shown to be disrupted in nondemented elderly with hippocampal atrophy, a risk factor for Alzheimer disease. Fifty nondemented, medically healthy elderly patients received baseline clinical diagnosis and cognitive testing; 2 years later, patients received a follow-up clinical diagnosis of normal, mild cognitive impairment, or probable Alzheimer disease. In all, 2 baseline variables, delayed paragraph recall and generalization performance, were predictive of follow-up outcome with sensitivity of 81% and specificity of 91%-better than the classification accuracy based on either of these measures alone. These preliminary results suggest that these behavioral tasks may be useful tools in predicting short-term cognitive outcome in nondemented elderly