The Ups and Downs of BACE1: Walking a Fine Line between Neurocognitive and Other Psychiatric Symptoms of Alzheimer’s Disease

Although neurocognitive deficit is the best-recognized indicator of Alzheimer’s disease (AD), psychotic and other noncognitive symptoms are the prime cause of institutionalization. BACE1 is the rate-limiting enzyme in the production of Aβ of AD, and one of the promising therapeutic targets in countering cognitive decline and amyloid pathology. Changes in BACE1 activity have also emerged to cause significant noncognitive neuropsychiatric symptoms and impairments of circadian rhythms, as evident from clinical trials and reports in transgenic models. In this study, we consider key characteristics of BACE1 with its contribution to neurocognitive deficit and other psychiatric symptoms of AD. We argue that a growing list of noncognitive mental impairments related to pharmacological modulation of BACE1 might present a major obstacle in clinical translation of emerging therapeutic leads targeting this protease. The adverse effects of BACE1 inhibition on mental health call for a revision of treatment strategies that assume indiscriminate inhibition of this key protease, and stress the need for further mechanistic and translational studies.

Alzheimer’s Disease: Pharmacotherapy of noncognitive symptoms

Alzheimer’s disease (AD) is a progressive and fatal dementia of unknown cause characterized by loss of cognitive and physical functioning, commonly with behavior or noncognitive symptoms. Noncognitive symptoms associated with Alzheimer's disease and related dementias consist of mood sisterbances, psychosis, altered sexual behavior, personality changes, agitation, aggression, pacing, wandering, , changed sleep patterns, and appetite disturbances. These noncognitive symptoms of dementia are common, disabling to both the patient and the carer. physicians will often play a major role in diagnosing and treating dementia and related disorders in the community. Accurate treatment of noncognitive symptoms is important. Accordingly, we reviewed the available pharmacotherapy in the clinical management of noncognitive symptoms of dementia.

Nonpharmacological Management of Behavioral and Psychological Symptoms of Dementia: What Works, in What Circumstances, and Why?

Objective Behavioral and psychological symptoms of dementia (BPSD) refer to the often distressing, noncognitive symptoms of dementia. BPSD appear in up to 90% of persons with dementia and can cause serious complications. Reducing the use of antipsychotic medications to treat BPSD is an international priority. This review addresses the following questions: What nonpharmacological interventions work to manage BPSD? And, in what circumstances do they work and why? Method A realist review was conducted to identify and explain the interactions among context, mechanism, and outcome. We searched electronic databases for empirical studies that reported a formal evaluation of nonpharmacological interventions to decrease BPSD. Results Seventy-four articles met the inclusion criteria. Three mechanisms emerged as necessary for sustained effective outcomes: the caring environment, care skill development and maintenance, and individualization of care. We offer hypotheses about how different contexts account for the success, failure, or partial success of these mechanisms within the interventions. Discussion Nonpharmacological interventions for BPSD should include consideration of both the physical and the social environment, ongoing education/training and support for care providers, and individualized approaches that promote self-determination and continued opportunities for meaning and purpose for persons with dementia.

Association of Cognitive and Noncognitive Symptoms of Delirium: A Study from Consultation-liaison Psychiatry Set-up

ABSTRACT Aims: This study aims to evaluate the cognitive functions of patients with delirium using Hindi Mental Status Examination (HMSE), to study the correlation of cognitive functions assessed by HMSE with noncognitive symptoms as assessed using Delirium Rating Scale-Revised 1998 (DRS-R-98) and to study the association of cognitive functions assessed using HMSE and DRS-R98. Methods: A total of 76 consecutive patients fulfilling the diagnosis of delirium were evaluated on DRS-R-98, HMSE, and Short Informant Questionnaire on Cognitive Decline in the Elderly (retrospective IQCODE). Results: The mean DRS-R-98 score 33.9 (standard deviation [SD] - 7.2) and the mean DRS-R-98 severity score was 25.9 (SD - 7.2). The mean score on HMSE was 19.3 (7.98). There were significant correlations of all the domains of HMSE with DRS-R-98 total score, DRS-R-98 severity score, DRS-R-98 cognitive subscale score, DRS-R-98 noncognitive domain subscale score, and DRS severity score without attention score. When the association of each item of DRS-R-98 and HMSE was evaluated, except for the items of delusions, lability of affect and motor retardation, there were significant negative association between all the items of DRS-R-98 and HMSE, indicating that higher severity of cognitive symptoms as assessed on HMSE is associated with higher severity of all the cognitive symptoms and most of the noncognitive symptoms as assessed by DRS-R-98. Conclusion: The present study suggests that attention deficits in patients with delirium influence the severity of cognitive and noncognitive symptoms of delirium. Further, the present study suggests an increase in the severity of cognitive symptoms in other domains is also associated with an increase in the severity of noncognitive symptoms of delirium.

The Impact of Perceived Knowledge of Dementia on Caregiver Burden

This study centered around 131 caregivers and their recipients to investigate whether the caregiver’s perceived knowledge of dementia may be a factor in reducing caregiver burden. We developed a questionnaire to measure this kind of knowledge. A significant relationship was shown between perceived knowledge and caregiver burden. Our multivariate analysis furthermore demonstrated that the caregivers’ self-assessed state of health also has a significant influence. A second regression model included the different aspects of perceived knowledge of our questionnaire and showed that certain aspects of perceived knowledge, especially concerning existing professional help services, noncognitive symptoms of dementia, and the importance of not neglecting one’s own personal needs, has an positive impact on caregiver burden.

Beyond the “C” in MCI: Noncognitive Symptoms in Amnestic and Non-amnestic Mild Cognitive Impairment

ABSTRACTIntroduction:How frequent and how clinically important are mood and behavioral symptoms among older adults with mild cognitive impairment (MCI)? Although these noncognitive behavioral symptoms (NCBS) are not represented in the diagnostic criteria for MCI, their clinical significance is increasingly recognized.Methods:To address this question, the authors identified a cohort of consecutively evaluated patients from a psychiatric hospital's outpatient memory clinic. These patients' records contained both a clinical assessment and a standardized set of evaluations including the Mini-Mental State Exam, the Neuropsychiatric Inventory (NPI), and the Geriatric Depression Scale. Using a standardized chart-review approach, the presence of any NPI-screened symptom was identified and the frequencies of specific NPI-screened symptoms were calculated for the Memory Clinic MCI cohort and for amnestic and non-amnestic MCI subgroups.Results:A total of 116 patient records were reviewed. Thirty-eight patients with MCI were identified. Twenty-two of these met criteria for amnestic MCI by Mayo Clinic criteria while 16 met criteria for non-amnestic MCI. At least one NPI-screened mood or behavioral symptom was present in 86.8% of these MCI patients. Depression/dysphoria (63.3%), apathy (60.5%), anxiety (47.4%), irritability (44.7%), and nighttime behaviors (42.1%) were the most frequent. While depression/dysphoria was distributed similarly between amnestic and non-amnestic subgroups, apathy was significantly more frequently associated with the amnestic subtype of MCI, and nighttime behaviors were more frequently associated with the non-amnestic subtype.Conclusion:Although the presence of NCBS is not required for a diagnosis of MCI, these symptoms are frequently present and constitute an important source of morbidity. Apathy and depression may be difficult to differentiate, but targeted treatment of depression may fail to address apathy. Recognizing the limitations of this preliminary study, the authors suggest that apathy may be more characteristic of amnestic MCI while nighttime behaviors may be more characteristic of non-amnestic MCI.