Istvan Boksay

The pre–mild cognitive impairment, subjective cognitive impairment stage of Alzheimer’s disease

Subjective cognitive impairment (SCI) has been a common, but poorly understood condition, frequently occurring in older persons.

Retrogenesis: clinical, physiologic, and pathologic mechanisms in brain aging, Alzheimer's and other dementing processes.

Abstract Data from clinical, electrophysiologic, neurophysiologic, neuroimaging and neuropathologic sources indicates that the progression of brain aging and Alzheimer’s disease (AD) deterioration proceeds inversely to human ontogenic acquisition patterns. A word for this process of degenerative developmental recapitulation, “retrogenesis”, has been proposed. These retrogenic processes provide new insights into the pathologic mechanism of AD deterioration. An understanding of retrogenic phenonmena can also result in insights into the applicability of retrogenic pathologic mechanisms for non-AD dementing disorders. Management strategies based upon retrogenesis have recently been proposed. Retrogenic pathophysiology also points to previously unexplored pharmacologic approaches to dementia prevention and treatment.

Addition of a frequency-weighted score to the Behavioral Pathology in Alzheimer's Disease Rating Scale: the BEHAVE-AD-FW: methodology and reliability.

The Behavioral Pathology in Alzheimers Disease Rating Scale (BEHAVE-AD) is a well-established instrument, designed to assess potentially remediable behavioral symptoms in Alzheimers disease (AD) patients as well as to evaluate treatment outcome. It consists of 25 symptoms grouped into seven categories. Each symptom is scored on the basis of severity on a four-point scale. A knowledgeable caregiver is queried and items are scored on the basis of symptoms noted in the preceding two weeks. Reliability, construct validity and criterion validity data for the BEHAVE-AD have previously been published. Because of the significance of psychopathology in dementia, it is necessary to optimally describe and define the nature, magnitude and prevalence of behavioral symptomatology. Accordingly, a frequency component was added to each of the 25 items of the BEHAVE-AD scale. The objective of the present report is to describe this new Behavioral Pathology in Alzheimers Disease Frequency-Weighted Severity Scale (BEHAVE-AD-FW) and to establish its inter-rater reliability. In this investigation the BEHAVE-AD-FW scale was administered to caregivers of 28 patients with either mildly impaired cognitive function or a dementia diagnosis. Two clinicians separately and independently rated the responses. Analyses determined that the intraclass correlation coefficients (ICCs) for the frequency component varied between 0.86 and 0.97 for each of the seven BEHAVE-AD categories (p(s) < 0.001). ICCs for the frequency-weighted scores (item severity score x item frequency score) ranged from 0.69 to 0.98 for the seven symptom categories (p(s) < 0.001). For the BEHAVE-AD-FW total scores, the ICC was 0.91 (P < 0.001). These results indicate that the frequency-weighted component is a reliable addition to the BEHAVE-AD scale.

Reliability of Routine Clinical Instruments for the Assessment of Alzheimer's Disease Administered by Telephone:

We investigated the reliability, using a telephone interview procedure, of cognitive, functional, and behavioral scales in an elderly population with normal aging and dementia. Two clinicians performed the assessments: one performed the assessments in a telephone interview format and the other conducted the assessments at the clinic. The telephone interview always preceded the clinic evaluation (2-30 days apart), and both clinicians were blind to any previous evaluations of the patient. The intraclass correlation coefficients between the telephone interview and the ratings obtained by a different clinician on the clinic evaluation varied between 0.92 and 0.98 (Ps ≤ .001) for comprehensive test scores. These results indicate that a telephone interview format, although not a substitute for a face-to-face diagnostic evaluation, is a reliable procedure for obtaining the assessment modalities studied. These findings are particularly important in aged and dementia research populations where personal contact may not always be feasible.

Behavioral Disturbances of Dementia: An Overview of Phenomenology and Methodologic Concerns

Behavioral disturbances in dementia are some of the most burden-some features with which the caregivers must cope. These symptoms are particularly important because they are likely to be responsive to both pharmacological and nonpharmacological intervention strategies. Before the 1980s, rating scales for patients suffering from dementia did not separate cognitive features from noncognitive behavioral symptoms. This was a major problem because the evolution and course of behavioral symptoms in dementias, such as Alzheimers disease, is different from the evolution and course of cognitive and cognition-related symptomatology. Before appropriate rating scales could be developed for the assessment of behavioral disturbances in dementia, the specific nature of these disturbances had to be described in the medical literature. Publications in the late 1980s described the specific behavioral disturbances occurring in dementia patients in detail for the first time. The rating scales that have been developed from these studies are as reliable as cognitive assessment measures. Instruments are now available that are based on information provided by the caregiver or that are based on observation of the patient made by the clinician. Construct validity, reliability, and the differences in methodology of these scales are compared in this overview. Using these scales will enable clinicians to assess pharmacological and nonpharmacological intervention strategies for behavioral symptoms in dementia with enhanced sensitivity.

Overview of methodologic issues for pharmacologic trials in mild, moderate, and severe Alzheimer's disease.

To address the issue of mild, moderate, and severe Alzheimers disease (AD), it is necessary to initially establish some agreement on terminology. In recent decades, these terms have frequently been defined using screening instrument scores with measures such as the Mini-Mental State Examination (MMSE). There are many problems with this approach, perhaps the most salient of which is that it has contributed to the total and tragic neglect of patients with severe AD. An alternative approach to the classification of AD severity is staging. This approach has advanced to the point where moderately severe and severe AD can be described in detail. Procedures for describing this previously neglected latter portion of AD have recently been extensively validated. Staging is also uniquely useful at the other end of the severity spectrum, in differentiating early aging brain/behavior changes, incipient AD, and mild AD. Temporally, with staging procedures, it is possible to track the course of AD approximately three times more accurately than with the MMSE. The net result of the advances in AD delineation is that issues such as prophylaxis, modification of course, treatment of behavioral disturbances, loss of ambulation, progressive rigidity, and the development of contractures in AD patients can now be addressed in a scientifically meaningful way that will hopefully bestow much benefit in AD patients and those who care for them.

The BEHAVE-AD Assessment System: A Perspective, A Commentary on New Findings, and A Historical Review

Background: Behavioral and psychological symptoms of dementia (BPSD) and associated disturbances in Alzheimers disease (AD) are a source of distress and burden for spouses, professional caregivers, and others with responsibilities for the care of individuals with AD. BPSD with behavioral disturbances are also associated with more rapid institutionalization and increased morbidity and mortality for persons with AD. Objectives: In this review and commentary, we discuss the history of the development of BPSD and behavioral disturbance assessments, which are distinct from those evaluating cognitive and functional symptoms of AD. In particular, we review the informant-based Behavioral Pathology in Alzheimers Disease Rating Scale (BEHAVE-AD), the related, potentially more sensitive, BEHAVE-AD Frequency-Weighted Severity Scale (BEHAVE-AD-FW), and the direct subject evaluation-based Empirical BEHAVE-AD Rating Scale (E-BEHAVE-AD). The kinds of medications that alleviate behavioral symptoms on these measures as well as the problems and possibilities for further advances with these medications are discussed. Finally, the importance of distinguishing BPSD and behavioral disturbance remediation in AD from the treatment of cognitive decline and other aspects of AD is emphasized in the context of appropriate assessment methodology. The objective of this paper is to provide a framework for further advances in the treatment of BPSD and associated behavioral disturbances in AD and, consequently, a framework for continuing improvements in the lives of individuals with AD and those who share the burden of the disease with the AD person.

ALZHEIMER'S DISEASE AND MEDICAL DISEASE CONDITIONS: A PROSPECTIVE COHORT STUDY

1. Jorstad EC, Hauer K, Becker C et al. Measuring the psychological outcomes of falling: A systematic review. J Am Geriatr Soc 2005;53:501–510. 2. Sattin RW, Lambert Huber DA, DeVito CA et al. The incidence of fall injury events among the elderly in a defined population. Am J Epidemiol 1990;131: 1028–1037. 3. Tinneti ME, Doucette J, Claus E et al. Risk factors for serious injury during falls by older persons in the community. J Am Geriatr Soc 1995;43:1214–1221. 4. Wittstein IS, Thiemann DR, Lima JAC et al. Neurohumoral features of myocardial stunning due to sudden emotional stress. N Engl J Med 2005;352:539– 548. 5. Kurisu S, Sato H, Kawagoe T et al. Tako-tsubo-like left ventricular dysfunction with ST-segment elevation: A novel cardiac syndrome mimicking acute myocardial infarction. Am Heart J 2002;143:448–455. 6. Tsuchihashi K, Ueshima K, Uchida T et al. Transient left ventricular apical ballooning without coronary artery stenosis: A novel heart syndrome mimicking acute myocardial infarction. J Am Coll Cardiol 2001;38:11–18. 7. Akashi YJ, Tejima T, Sakurada H et al. Left ventricular rupture associated with Takotsubo cardiomyopathy. Mayo Clin Proc 2004;79:821–824. 8. Ako J, Takenaka K, Uno K et al. Reversible left ventricular systolic dysfunctionFreversibility of coronary microvascular abnormality. Jpn Heart J 2001; 42:355–363.

Do many of the behavioral and psychological symptoms of dementia constitute a distinct clinical syndrome? Current evidence using the BEHAVE-AD

The Behavioral Pathology in Alzheimers Disease Rating Scale (BEHAVE-AD) was specifically designed to assess behavioral and psychological symptoms of dementia (BPSD) that would be remediable to both psychologic and pharmacologic intervention. Furthermore, the BEHAVE-AD was designed to assess categories of symptoms that would respond in a cohesive (syndrome) manner in dementia patients, independently of effects of interventions on cognition and functioning. Current data indicate that the BEHAVE-AD does indeed assess a cohesive, cognition- and function independent syndrome in AD and in related dementias that is responsive to psychologic and appropriate pharmacologic intervention. Evidence is also increasing for differential responsiveness of this BPSD syndrome to select pharmacologic agents compared with nonspecific psychologic (placebo) intervention. This article reviews the evidence for this BPSD syndrome in dementia patients, as assessed with the BEHAVE-AD.

New and Promising Modalities for Assessment of Behavioral and Psychological Symptoms of Dementia

Behavioral and psychological symptoms of dementia (BPSD; Finkel et al., 1998) are receiving increased attention in the medical and scientific literature. These symptoms are a principal cause of distress and disability among patients with dementia and their caregivers. Numerous therapeutic studies examining the treatment of these symptoms are being conducted.