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Background: Little is known with respect to behavioral markers of subjective cognitive decline (SCD), a condition initially described in association with Global Deterioration Scale (GDS) stage 2. Objective: Two-year interval behavioral markers were investigated herein. Methods: Subjects from a published 7-year outcome study of GDS stage 2 subjects were selected. This study had demonstrated a hazard ratio of 4.5 for progression of GDS stage 2, in comparison with GDS stage 1 (no subjective or objective cognitive decline) subjects, after controlling for demographic and temporal variables. Because GDS 2 subjects have previously demonstrated impairment in comparison with healthy persons free of complaints, we herein suggest the terminology "SCD(I)" for these persons. 98 SCD(I) persons, 63 women and 35 men, mean baseline age, 67.12 +/- 8.75 years, with a mean educational background of 15.55 +/- 2.60 years, and mean baseline MMSE scores of 28.9 +/- 1.24 were followed for 2.13 +/- 0.30 years. Results: Observed annual decline on the GDS was 6.701% per annum, very close to a 1986 published estimate. At follow up, the MMSE, and 7 of 8 psychometric tests did not decline significantly. Of 21 Hamilton Depression Scale items, 2 improved and the remainder were unchanged. Anxieties declined from multiple perspectives. The Brief Cognitive Rating Scale (BCRS) declined significantly (p < 0.001), with component declines in Remote memory (p < 0.01), and Functioning/self-care (p = 0 .01). Conclusion: SCD(I) persons decline at an annual rate of approximately 6.7%/year from several recent studies. The BCRS assessments and the Digit Symbol Substitution Test can be sensitive measures for future studies of progression mitigation.

Background/Aims: The aim was to examine added benefits of a Comprehensive, Individualized, Person-Centered Management (CI-PCM) program to memantine treatment. Methods: This was a 28-week, clinician-blinded, randomized, controlled, parallel-group study, with a similar study population, similar eligibility criteria, and a similar design to the memantine pivotal trial of Reisberg et al. [N Engl J Med 2003;348:1333-1341]. Twenty eligible community-residing Alzheimer disease (AD) subject-caregiver dyads were randomized to the CI-PCM program (n = 10) or to usual community care (n = 10). Primary outcomes were the New York University Clinician's Interview-Based Impression of Change Plus Caregiver Input (NYU-CIBIC-Plus), assessed by one clinician set, and an activities of daily living inventory, assessed by a separate clinician set at baseline and at weeks 4, 12, and 28. Results: Primary outcomes showed significant benefits of the CI-PCM program at all post-baseline evaluations. Improvement on the NYU-CIBIC-Plus in the management group at 28 weeks was 2.9 points over the comparator group. The memantine 2003 trial showed an improvement of 0.3 points on this global measure in memantine-treated versus placebo-randomized subjects at 28 weeks. Hence, globally, the management program intervention benefits were 967% greater than memantine treatment alone. Conclusion: These results are approximately 10 times those usually observed with both nonpharmacological and pharmacological treatments and indicate substantial benefits with the management program for advanced AD persons.

The Behavioral Pathology in Alzheimer's 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.

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.

The clinical impact of Alzheimer's disease pathology at biopsy was investigated in 56 cognitively impaired patients undergoing shunt surgery for idiopathic normal pressure hydrocephalus (NPH). Cognition was measured by means of the global deterioration scale (GDS), the mini mental status examination (MMSE) and a battery of six psychometric tests. Gait was assessed using objective measurements of velocity and the ambulatory index (AI). The prevalence of cases exhibiting neuritic plaques (positive biopsies) increased in parallel with dementia severity from 18% for patients with GDS 3 to 75% for patients with GDS scoresor =6. Patients with positive biopsies were more cognitively impaired (higher GDS and lower MMSE scores) as well as more gait impaired (higher AI scores and slower velocities) than patients with negative biopsies. After surgery, gait velocity and AI scores improved significantly and to a comparable degree for patients with and without positive biopsies. Similar proportions of positive and negative biopsy patients also had improved gait as assessed by means of subjective video tape comparisons. There were no significant differences between the biopsy groups in the magnitude of postoperative psychometric change or in the proportion of cases exhibiting improved urinary control. Alzheimer's disease pathology is a common source of comorbidity in older patients with idiopathic NPH where it contributes to the clinical impairment associated with this disorder. For patients accurately diagnosed with NPH, concomitant Alzheimer's disease pathology does not strongly influence the clinical response to shunt surgery.

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 ( P's ≤ .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.

Background: Behavioral and psychological symptoms of dementia (BPSD) and associated disturbances in Alzheimer's 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 Alzheimer's 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.

To address the issue of mild, moderate, and severe Alzheimer's 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-Menal 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 distrubances, 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.

containing 20 mg/L of resveratrol produced effects similar to those of resveratrol administration in WT mice, neither red wine containing 3.1 mg/ L of resveratrol nor white wine exhibited such effects in WT mice. Resveratrol was undetectable in the hippocampus ofWTmice administered resveratrol and red wine containing 20 mg/L of resveratrol. Conclusions: These observations strongly suggest that resveratrol may increase hippocampal IGF-I production via sensory neuron stimulation in the GI tract, thereby improving cognitive function and showing anti-depressant effect in mice. These results may explain at least in part the beneficial effects of moderate consumption of red wine on cognitive function in humans.

The prevalence rate of depression in medical long-term care facilities is high but varies over a large range. One source of variation may be differences in the underlying incidence rates. A cohort of 104 new admissions was followed for one year and showed and incidence rate of approximately 14%. This rate is comparable to the only other published study and suggests that incidence rates may be more uniform than expected from the range of prevalence reports.

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 ∼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.

The lithium literature indicates that geriatric psychiatric patients are particularly at risk for developing serious neurotoxic side-effects. There is currently no reliable method for predicting which patients are at heightened risk for this adverse development. There is evidence that the adjunctive monitoring of intra-erythrocyte (RBC) lithium levels may offer early indications that such toxicity is impending. Applications of such measurements are shown in two case reports which offer preliminary support for the value of RBC levels.

SummaryThe Behavioral Pathology in Alzheimer’s Disease Rating Scale (BEHAVE-AD) is a well-established instrument, designed to assess potentially remediable behavioral symptoms in Alzheimer’s 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 symptomalogy. 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 Alzheimer’s 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 (ps < 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 (ps < 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.

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.

Behavioral disturbances in dementia are some of the most burdensome 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 Alzheimer's 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 diturbances 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.

The reliability of the DSM-III diagnostic system was assessed in a medical long-term care facility population that was recently seen in psychiatric consultation. Six standard rating scales were used to determine interrater agreement for perceiving psychopathology prior to selecting diagnoses. The findings were that six major diagnostic groups could be accurately distinguished from one another: no disorder; organic mental disorders; affective disorders; paranoid disorders; schizophrenia and psychotic disorders not elsewhere classified; and a mixed group of other diagnoses that occurred in low frequency in this study population. The interrater reliability (kappa = 0.64–0.70) was comparable to that found in the general psychiatric population.

Clinical assessment of psychopathology includes quantifying symptoms on rating scales. Caution must be used in applying standardized instruments to new populations because their reliability may alter considerably. This study assesses the interrater reliability of six well-known rating scales when applied to patients residing in a medical long-term care facility. The scales include measures of depression, psychosis and cognitive impairment. The specific scales used were: Hamilton Depression Scale; Brief Psychiatric Rating Scale; Mini-Mental State Examination; Mental Status Questionnaire; Global Deterioration Scale; and Brief Cognitive Rating Scale.