Faculty Bibliography

Background: Impairment in functional capacities is an integral domain in AD presentation, diagnosis and progression. Among many functional scales for AD assessment, the Functional Assessment Staging scale (FAST) (Table 1) uniquely: (1) charts the entire course of AD, from normal aging to most severe AD; (2) has relevance for AD diagnosis and differential diagnosis; and (3) is brief and easy to utilize. Methods: Reliability, validity, and utility of the FAST have been documented in worldwide studies and clinical settings. Results: The FAST has excellent reliability (e.g., Foster et al., Int J Geriatr. Psychiatry,1988; Sclan and Reisberg, Int. Psychogeriatr., 1992). Concurrent validity has been demonstrated with: cognitive assessments across the severity spectrum (e.g., Reisberg, et al., Int. Psychogeriatr., 1992; Shimada, et al., Psychogeriatrics, 2003; Auer et al., JAGS, 1994); other dementia scales (Na et al., JAD, 2010); and neurologic assessments (Franssen and Reisberg, Int. Psychogeriatr., 1997). Criterion validity investigations have indicated superiority of the FAST in comparison with the MMSE, in tracking the course of AD. E.g., in a 5 year prospective longitudinal study of AD course, the FAST accounted for w 2x the temporal variance of the MMSE (Reisberg, et al., Int. Psychogeriatr., 1996). Also, in a range where the MMSE is zero, the FAST demonstrated very robust relationships to AD neuropathology (e.g., r = 0.9 [p 0.01], with hippocampal cornu ammonis neuronal loss), (Bobinski, et al., J. Neuropathol. Exp. Neurol., 1997). Additionally, in a pivotal trial, associated with worldwide approvals of memantine for AD treatment, FAST scores were sensitive to the intervention, MMSE change was not (Reisberg, et al., N Engl J Med., 2003). The FAST has shown widespread utility (e.g., usage mandated by U.S.A. Medicare since 1998, and the U.S.A. Veterans Administration System, since 2008). Conclusions: As noted in a Korean publication, the FAST is a rapid and easy to use staging tool with excellent validity. it. successfully measure[ s] detailed function throughout the entire course of AD. the FAST is composed of simple . and easy to understand sentences

BACKGROUND: Subjective cognitive impairment (SCI) in older persons without manifest symptomatology is a common condition with a largely unclear prognosis. We hypothesized that (1) examining outcome for a sufficient period by using conversion to mild cognitive impairment (MCI) or dementia would clarify SCI prognosis, and (2) with the aforementioned procedures, the prognosis of SCI subjects would differ significantly from that of demographically matched healthy subjects, free of SCI, termed no cognitive impairment (NCI) subjects. METHODS: A consecutive series of healthy subjects, aged > or =40 years, presenting with NCI or SCI to a brain aging and dementia research center during a 14-year interval, were studied and followed up during an 18-year observation window. The study population (60 NCI, 200 SCI, 60% female) had a mean age of 67.2 +/- 9.1 years, was well-educated (mean, 15.5 +/- 2.7 years), and cognitively normal (Mini-Mental State Examination, 29.1 +/- 1.2). RESULTS: A total of 213 subjects (81.9% of the study population) were followed up. Follow-up occurred during a mean period of 6.8 +/- 3.4 years, and subjects had a mean of 2.9 +/- 1.6 follow-up visits. Seven NCI (14.9%) and 90 SCI (54.2%) subjects declined (P < .0001). Of NCI decliners, five declined to MCI and two to probable Alzheimer's disease. Of SCI decliners, 71 declined to MCI and 19 to dementia diagnoses. Controlling for baseline demographic variables and follow-up time, Weibull proportional hazards model revealed increased decline in SCI subjects (hazard ratio, 4.5; 95% confidence interval, 1.9-10.3), whereas the accelerated failure time model analysis with an underlying Weibull survival function showed that SCI subjects declined more rapidly, at 60% of the rate of NCI subjects (95% confidence interval, 0.45-0.80). Furthermore, mean time to decline was 3.5 years longer for NCI than for SCI subjects (P = .0003). CONCLUSIONS: These results indicate that SCI in subjects with normal cognition is a harbinger of further decline in most subjects during a 7-year mean follow-up interval. Relevance for community populations should be investigated, and prevention studies in this at-risk population should be explored

BACKGROUND: Subjective cognitive impairment (SCI) has been a common, but poorly understood condition, frequently occurring in older persons. METHODS: The past and the emerging literature on SCI and synonymously named conditions is reviewed. RESULTS: Findings include: (1) There is support from at least one longitudinal study for a long-standing concept of SCI as a pre-mild cognitive impairment (MCI) condition lasting approximately 15years. (2) There are complex relationships between SCI and depression and anxiety. (3) Differences in SCI subjects from age-matched non-SCI persons are being published in terms of cognitive tests, hippocampal gray matter density, hippocampal volumes, cerebral metabolism, and urinary cortisol levels. Psychometric and dementia test score differences between SCI and MCI subjects have long been evident. (4) Predictive electrophysiologic features of subsequent decline in SCI subjects are being published. CONCLUSIONS: Studies of therapeutic agents in SCI treatment and resultant Alzheimer's disease prevention appear to be feasible. These trials are also necessary from a public health perspective

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