The COVID-19 pandemic is causing global morbidity and mortality, straining health systems,

Psychotic symptoms, delusions and hallucinations, occur in approximately 50% of individuals with Alzheimer’s disease (AD) (AD with psychosis [AD + P]). Pharmacotherapies for AD + P have limited efficacy and can increase short-term mortality. These observations have motivated efforts to identify the underlying biology of AD + P. Psychosis in AD indicates a more severe phenotype, with more rapid cognitive decline beginning even before psychosis onset. Neuroimaging studies suggest that AD + P subjects demonstrate greater cortical synaptic impairments than AD subjects without psychosis, reflected in reduced gray matter volume, reduced regional blood flow, and reduced regional glucose metabolism. Neuroimaging and available postmortem evidence further indicate that the impairments in AD + P, relative to AD subjects without psychosis, are localized to neocortex rather than medial temporal lobe. Neuropathologic studies provide consistent evidence of accelerated accumulation of hyperphosphorylated microtubule associated protein tau in AD + P. Finally, studies of familial aggregation of AD + P have established that the risk for psychosis in AD is, in part, genetically mediated. Although no genes are established as associated with AD + P, the first genome-wide association study of AD + P has generated some promising leads. The study of the neurobiology of AD + P is rapidly accelerating and may be poised for translational discovery. This process can be enhanced by identifying points of convergence and divergence with the neurobiology of AD proper and of schizophrenia, by innovative extension of current approaches, and by development of relevant animal models.

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Working memory deficits are common among individuals with Alzheimer’s dementia (AD) or mild cognitive impairment (MCI). Yet, little is known about the mechanisms underlying these deficits. Theta-gamma coupling—the modulation of high-frequency gamma oscillations by low-frequency theta oscillations—is a neurophysiologic process underlying working memory. We assessed the relationship between theta-gamma coupling and working memory deficits in AD and MCI. We hypothesized that: (1) individuals with AD would display the most significant working memory impairments followed by MCI and finally healthy control (HC) participants; and (2) there would be a significant association between working memory performance and theta-gamma coupling across all participants. Ninety-eight participants completed the N-back working memory task during an electroencephalography (EEG) recording: 33 with AD (mean ± SD age: 76.5 ± 6.2), 34 with MCI (mean ± SD age: 74.8 ± 5.9) and 31 HCs (mean ± SD age: 73.5 ± 5.2). AD participants performed significantly worse than control and MCI participants on the 1- and 2-back conditions. Regarding theta-gamma coupling, AD participants demonstrated the lowest level of coupling followed by the MCI and finally control participants on the 2-back condition. Finally, a linear regression analysis demonstrated that theta-gamma coupling (β = 0.69, p < 0.001) was the most significant predictor of 2-back performance. Our results provide evidence for a relationship between altered theta-gamma coupling and working memory deficits in individuals with AD and MCI. They also provide insight into a potential mechanism underlying working memory impairments in these individuals.

This study demonstrated impaired in vivo DLPFC plasticity in patients with AD. The findings support the use of DLPFC plasticity as a measure of DLPFC function and a potential treatment target to enhance DLPFC function and working memory in patients with AD.

The Electrophysiology Professional Interest Area (EPIA) and Global Brain Consortium endorsed recommendations on candidate electroencephalography (EEG) measures for Alzheimer's disease (AD) clinical trials. The Panel reviewed the field literature. As most consistent findings, AD patients with mild cognitive impairment and dementia showed abnormalities in peak frequency, power, and “interrelatedness” at posterior alpha (8‐12 Hz) and widespread delta (< 4 Hz) and theta (4‐8 Hz) rhythms in relation to disease progression and interventions. The following consensus statements were subscribed: (1) Standardization of instructions to patients, resting state EEG (rsEEG) recording methods, and selection of artifact‐free rsEEG periods are needed; (2) power density and “interrelatedness” rsEEG measures (e.g., directed transfer function, phase lag index, linear lagged connectivity, etc.) at delta, theta, and alpha frequency bands may be use for stratification of AD patients and monitoring of disease progression and intervention; and (3) international multisectoral initiatives are mandatory for regulatory purposes.

Introduction:Behavioural and psychological symptoms of dementia (BPSD) include agitation and aggression in people with dementia. BPSD is common on inpatient psychogeriatric units and may prevent individuals from living at home or in residential/nursing home settings. Several drugs and non-pharmacological treatments have been shown to be effective in reducing behavioural and psychological symptoms of dementia. Algorithmic treatment may address the challenge of synthesizing this evidence-based knowledge.Methods:A multidisciplinary team created evidence-based algorithms for the treatment of behavioural and psychological symptoms of dementia. We present drug treatment algorithms for agitation and aggression associated with Alzheimer’s and mixed Alzheimer’s/vascular dementia. Drugs were appraised by psychiatrists based on strength of evidence of efficacy, time to onset of clinical effect, tolerability, ease of use, and efficacy for indications other than behavioural and psychological symptoms of dementia.Results:After baseline assessment and discontinuation of potentially exacerbating medications, sequential trials are recommended with risperidone, aripiprazole or quetiapine, carbamazepine, citalopram, gabapentin, and prazosin. Titration schedules are proposed, with adjustments for frailty. Additional guidance is given on use of electroconvulsive therapy, optimization of existing cholinesterase inhibitors/memantine, and use of pro re nata medications.Conclusion:This algorithm-based approach for drug treatment of agitation/aggression in Alzheimer’s/mixed dementia has been implemented in several Canadian Hospital Inpatient Units. Impact should be assessed in future research.

The COVID-19 pandemic has significantly affected the elderly and particularly individuals with Alzheimer’s disease and related disorders (ADRD). Behavioral and psychological symptoms of dementia (BPSD) are heterogeneous and common in individuals with ADRD and are associated with more severe illness. However, unlike the cognitive symptoms of ADRD that are usually progressive, BPSD may be treatable. Individuals with BPSD are facing unique challenges during the pandemic due to the inherent nature of the illness and the biological and psychosocial impacts of COVID-19. These challenges include a higher risk of severe COVID-19 infection in individuals with BPSD due to their frailty and medical vulnerability, difficulty participating in screening or testing, and adhering to infection control measures such as physical distancing. Further, biological effects of COVID-19 on the brain and its psychosocial impact such as isolation and disruption in mental health care are likely to worsen BPSD. In this paper, we discuss these challenges and strategies to manage the impact of COVID-19 and to effectively care for individuals with BPSD in community, long-term care, or hospital settings during the pandemic. Despite the ongoing uncertainty associated with this pandemic, we can reduce its impact on individuals with BPSD with a proactive approach.