Faculty Bibliography

OBJECTIVE--To assess the possible association between functional decline and noncognitive neurologic signs in the severe stages of Alzheimer's disease (AD). DESIGN--Case series. SETTING--Subjects from a dementia research referral center, longitudinally followed, when necessary, into residential home and nursing home settings. PATIENTS--A consecutive sample of 56 patients (16 men, 40 women; mean age, 74.6 years) with a clinical diagnosis of probable AD in the moderately severe and severe stages. MAIN OUTCOME MEASURE--For global dementia severity, the Global Deterioration Scale and Mini-Mental State examination; for functional assessment, the Functional Assessment Staging Scale; and for assessment of neurologic function, nine release signs (primitive reflexes), 10 measures of extrapyramidal function, and five measures of pyramidal function, including deep-tendon reflexes and plantar signs. Changes in activity or presence of neurologic signs were rated on a seven-point scale. Results were analyzed in terms of prevalence and magnitude of change in relation to functional impairment. RESULTS--Prevalence and mean scores of certain release signs, certain extrapyramidal measures commonly referred to as bradykinesia, and certain pyramidal signs showed significant associations with the magnitude of functional impairment. Other neurologic measures, for example, the palmomental reflex, and certain extrapyramidal measures commonly seen in Parkinson's disease, including the glabellar blink reflex, cogwheeling, tremor, shuffling gait, and festination, did not show significant increments with continuing functional decline in AD. CONCLUSIONS--Functional decline in the advanced stages of AD appears to be associated with a particular combination of progressive cortical, extrapyramidal, and pyramidal system dysfunction. The characteristics of this neurologic syndrome of the severe stages of AD differ from those of other neurologic disorders. For example, the pattern of extrapyramidal system disease is different from that seen in Parkinson's disease. The neurologic syndrome of the severe stages of AD is amenable to description and deserves further investigation

Phenomenologic, cross-sectional and longitudinal studies have resulted in the identification of characteristic stages of normal aging and progressive Alzheimer's disease (AD). A staging system resulting from these studies is known as the ''GDS Staging System.'' Three optimally concordant and potentially independent clinical rating instruments are incorporated in this staging system, the Global Deterioration Scale (GDS), the Brief Cognitive Rating Scale (BCRS) and the Functional Assessment Staging measure (FAST). Definitions of each of the elements of this staging system as well as reliability and concurrent validity data have been published. Clear advantages of the GDS Staging System over other available staging measures include: (1) readily interpretable and clinically meaningful stages and substages; (2) improved definition of the boundaries of normal aging and incipient AD, and (3) the ability to chart the course of the severely impaired, conventionally ''untestable,'' portion of AD. Widespread usage of this staging system can potentially advance current research and clinical understanding of normal brain aging and the nature, course and treatment of AD and related conditions

Research on the nature of clinical symptomatology in AD indicates that two fundamentally different types of symptoms are identifiable. Symptoms within each of these two domains have common characteristics. The first symptomatic domain has been termed the 'cognitive domain' and the second the 'noncognitive behavioral domain.' Symptoms and losses in the cognitive domain occur invariably and progressively with the advance of AD over time. Symptoms in the behavioral domain do not invariably occur in AD and do not progress monotonically with the advance in AD over time. However, characteristic behavioral domain symptoms can be described over the course of AD. The two symptomatic domains are likely to differ not only in nature and progression in AD, but also in underlying pathophysiology and in terms of possible treatment modalities. They also pose fundamentally different issues of assessment in AD. These distinct factors necessitate the separate assessment of the two symptomatic domains in AD treatment trials. Judgments of efficacy and utility in remediating either symptomatic domain in AD should take into consideration the effects of treatment on both cognitive domain and behavioral domain symptoms separately and interactively. Appropriate assessment procedures are discussed