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

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

Positron emission tomographic studies of cerebral glucose metabolism have shown high diagnostic specificity in distinguishing among the degenerative dementias and differentiating between Alzheimer's disease (AD) and normal aging. The current investigation was undertaken to characterize the regional glucose metabolic deficits in AD, using cross-sectional and longitudinal study designs. All subjects met the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria for AD (n = 45) or were normal (n = 20), and the AD subjects were subdivided into incipient and mild AD and moderate plus moderately severe subgroups based on the Global Deterioration Scale. The subjects underwent a non-contrast computed tomographic scan and a positron emission tomographic (PETT VI) scan. The AD subjects (n = 14) and normal control subjects (n = 15) received evaluations 2 to 3 years after baseline study. The brain regions that show glucose metabolic deficits cross-sectionally (temporal and parietal association areas, with lesser degrees of deficit in subcortical gray matter structures), over the stages of AD, also show further deficits longitudinally within the same AD subjects. The reduction in glucose metabolism is greater than would be expected from the degree of brain atrophy. The glucose metabolic deficits are discussed in the context of neuropathologic findings and neurotransmitter deficits in AD

The clinical symptoms of Alzheimer's disease must be assessed and characterized comprehensively to confirm a diagnosis of dementia, to follow the course of the illness, and to evaluate the effects of treatment. Comprehensive assessment measures are multi-item scales that evaluate the various core cognitive symptoms of dementia and that provide a total score representing the overall magnitude of cognitive impairment. Neuropsychologic test batteries provide more detailed, objective evaluations of the various cognitive functions that are impaired. Global staging methods provide a single measure of the stage or severity of dementia, which is useful for tracking the clinical course and for comparisons among different studies. Scales to assess activities of daily living (basic physical functions and more complex instrumental activities) provide the most clinically relevant information regarding a patient's capacity to function in daily life. Finally, noncognitive behavioral symptom scales evaluate the secondary dementia symptoms (depression, agitation, hallucinations, delusions, etc.) that provide the greatest difficulty for patient management

Deep tendon reflexes, plantar responses, muscle tone, and release signs were studied as 14 individual clinical variables and as five summary variables in 135 aged subjects, including 27 control subjects, 20 subjects with mild cognitive impairment, and 88 subjects with successive stages of probable Alzheimer's disease. Changes in activity of elicited responses were rated on a seven-point scale. Results were analyzed both as prevalence and mean degree of change in activity. Rating on a variable combining all 14 individual variables was significantly higher in a group with mild cognitive impairment than in a control group. Subjects with an early stage of Alzheimer's disease had both higher prevalence of increased activity and increased mean scores of deep tendon reflexes and muscle tone. They had a higher prevalence of increased activity on a variable combining three release signs. Patients with a late stage of Alzheimer's disease had significantly increased prevalence and mean scores of muscle tone and grasping and sucking reflexes compared with control subjects and patients with the early stage of Alzheimer's disease

Meta-analysis of 38 studies compared Wechsler IQ scores in affective disorder (A), lateralized right (RH), left (LH) and bilateral/diffuse (BI) brain damage. A, RH, and BI had lower PIQ than VIQ. In A and BI groups the PIQ/VIQ ratio was identical, whereas each differed significantly from the RH group which revealed a much lower PIQ/VIQ ratio. Similarity of neuropsychological profiles of A and RH patients is often interpreted as indicating predominant right-hemisphere involvement in affective disorder. The present findings suggest an alternative interpretation is possible: i.e., the presence of bilateral/diffuse CNS involvement in affective disorder. We do not believe that our findings strongly support one interpretation over the other. In future research, both possibilities should be considered.