Faculty Bibliography

An extensive literature reports changes in quantitative electroencephalogram (QEEG) with aging and a relationship between magnitude of changes and degree of clinical deterioration in progressive dementia. Longitudinal studies have demonstrated QEEG differences between mild cognitively impaired (MCI) elderly who go on to decline and those who do not. This study focuses on normal elderly with subjective cognitive complaints to assess the utility of QEEG in predicting future decline within 7 years. Forty-four normal elderly received extensive clinical, neurocognitive and QEEG examinations at baseline. All study subjects (N = 44) had only subjective complaints but no objective evidence of cognitive deficit (evaluated using the Global Deterioration Scale [GDS] score, GDS stage = 2) at baseline and were re-evaluated during 7-9 year follow-up. Baseline QEEGs of Decliners differed significantly (p < 0.0001, by MANOVA) from Non-Decliners, characterized by increases in theta power, slowing of mean frequency, and changes in covariance among regions, especially on the right hemisphere. Using logistic regression, an R2 of 0.93 (p < 0.001) was obtained between baseline QEEG features and probability of future decline, with an overall predictive accuracy of 90%. These data indicate high sensitivity and specificity for baseline QEEG as a differential predictor of future cognitive state in normal, subjectively impaired elderly

The diagnosis of Alzheimer's disease (AD) in patients with mild cognitive impairment (MCI) is limited because it is based on non-specific behavioral and neuroimaging findings. The lesions of Alzheimer's disease: amyloid beta (Abeta) deposits, tau pathology and cellular oxidative damage, affect the hippocampus in the earlier stages causing memory impairment. In a 2-year longitudinal study of MCI patients and normal controls, we examined the hypothesis that cerebrospinal fluid (CSF) markers for these pathological features improve the diagnostic accuracy over memory and magnetic resonance imaging (MRI)-hippocampal volume evaluations. Relative to control, MCI patients showed decreased memory and hippocampal volumes and elevated CSF levels of hyperphosphorylated tau and isoprostane. These two CSF measures consistently improved the diagnostic accuracy over the memory measures and the isoprostane measure incremented the accuracy of the hippocampal volume achieving overall diagnostic accuracies of about 90%. Among MCI patients, over 2 years, longitudinal hippocampal volume losses were closely associated with increasing hyperphosphorylated tau and decreasing amyloid beta-42 levels. These results demonstrate that CSF biomarkers for AD contribute to the characterization of MCI

BACKGROUND: This study is an extension of a 28-week, randomized, double-blind, placebo-controlled study of memantine in 252 patients with moderate to severe Alzheimer disease. OBJECTIVE: To evaluate long-term memantine treatment in moderate to severe Alzheimer disease. DESIGN, SETTING, AND PATIENTS: Open-label, 24-week extension trial. Raters remained blind to the patients' initial study treatment. Patients (n = 175) were enrolled from the previous double-blind study in an outpatient setting. INTERVENTION: Twenty mg of memantine was given daily. MAIN OUTCOME MEASURES: Efficacy assessments from the double-blind study were continued and safety parameters were monitored. RESULTS: Patients who switched to memantine treatment from their previous placebo therapy experienced a significant benefit in all main efficacy assessments (functional, global, and cognitive) relative to their mean rate of decline with placebo treatment during the double-blind period (P<.05). The completion rate for the extension phase of the study was high (78%) and the favorable adverse event profile for memantine therapy was similar to that seen in the double-blind study. CONCLUSION: These results extend previous findings that demonstrated the efficacy and safety of memantine in the treatment of patients with moderate to severe Alzheimer disease

Mild cognitive impairment is a syndrome defined as cognitive decline greater than expected for an individual's age and education level but that does not interfere notably with activities of daily life. Prevalence in population-based epidemiological studies ranges from 3% to 19% in adults older than 65 years. Some people with mild cognitive impairment seem to remain stable or return to normal over time, but more than half progress to dementia within 5 years. Mild cognitive impairment can thus be regarded as a risk state for dementia, and its identification could lead to secondary prevention by controlling risk factors such as systolic hypertension. The amnestic subtype of mild cognitive impairment has a high risk of progression to Alzheimer's disease, and it could constitute a prodromal stage of this disorder. Other definitions and subtypes of mild cognitive impairment need to be studied as potential prodromes of Alzheimer's disease and other types of dementia

Planning is being initiated for the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders 5th ed. (DSM-V). Therefore, the dementia diagnosis criteria in the American Psychiatric Association's DSM-IV-TR (4th ed, text revision, 2000) have been compared with the World Health Organization's International Classification of Diseases (10th revision, 1992). Critiques are based primarily on (a) internal consistency and validity of the classification, (b) historical development of the field, (c) conclusions of consensus conferences, and (d) current knowledge and practice. It is suggested that (1) the entire category be labeled 'cognitive disorders,' to better characterize this group of disorders, (2) there is no longer any scientific basis for the presenile versus senile dementia dichotomy at age 65, (3) Alzheimer's disease no longer should have unique status as a 'diagnosis of exclusion,' (4) future manuals should incorporate knowledge regarding the clinical manifestation and course of Alzheimer's disease and other dementias, and (5) the classification 'Pick's disease' should be broadened to 'frontotemporal dementias.' DSM-V should incorporate continuing advances in the neuroscience knowledge base and understanding of these disorders

Since many Parkinson's disease (PD) subjects develop dementia, we determined whether the correlation between functional and cognitive decline seen in Alzheimer's disease (AD) is seen in PD. Seventy-five PD subjects with and without dementia and 103 AD/MCI subjects underwent the Functional Assessment Staging (FAST), the Global Deterioration Scale (GDS), the UPDRS motor portion, and the MMSE. In AD/MCI subjects, changes in FAST and GDS scores correlated with MMSE (rho=-0.814, P<0.001; rho=-0.840, P<0.001, respectively). In PD subjects, the FAST and GDS also correlated with MMSE (rho=-0.675, P<0.001; rho=-0.647, P<0.001, respectively). The UPDRS correlated with the GDS and FAST more closely in PD than in AD. Similar to AD, functional declines in PD correlates with cognitive decline and may be influenced by motor disability in PD.