Cognition Before and After COVID-19 Disease in Older Adults: An Exploratory Study.

BACKGROUND: Older age is a major risk factor for severe COVID-19 disease which has been associated with a variety of neurologic complications, both acutely and chronically. OBJECTIVE: We sought to determine whether milder COVID-19 disease in older vulnerable individuals is also associated with cognitive and behavioral sequelae. METHODS: Neuropsychological, behavioral, and clinical outcomes before and after contracting COVID-19 disease, were compared in members of two ongoing longitudinal studies, the Arizona APOE Cohort and the national Alzheimer's Disease Research Center (ADRC). RESULTS: 152 APOE and 852 ADRC cohort members, mean age overall roughly 70 years, responded to a survey that indicated 21 APOE and 57 ADRC members had contracted COVID-19 before their ensuing (post-COVID) study visit. The mean interval between test sessions that preceded and followed COVID was 2.2 years and 1.2 years respectively for the APOE and ADRC cohorts. The magnitude of change between the pre and post COVID test sessions did not differ on any neuropsychological measure in either cohort. There was, however, a greater increase in informant (but not self) reported cognitive change in the APOE cohort (p = 0.018), but this became nonsignificant after correcting for multiple comparisons. CONCLUSION: Overall members of both cohorts recovered well despite their greater age-related vulnerability to more severe disease.

Remote versus face-to-face neuropsychological testing for dementia research: a comparative study in people with Alzheimer's disease, frontotemporal dementia and healthy older individuals.

OBJECTIVES: We explored whether adapting neuropsychological tests for online administration during the COVID-19 pandemic was feasible for dementia research. DESIGN: We used a longitudinal design for healthy controls, who completed face-to-face assessments 3-4 years before remote assessments. For patients, we used a cross-sectional design, contrasting a prospective remote cohort with a retrospective face-to-face cohort matched for age/education/severity. SETTING: Remote assessments were conducted using video-conferencing/online testing platforms, with participants using a personal computer/tablet at home. Face-to-face assessments were conducted in testing rooms at our research centre. PARTICIPANTS: The remote cohort comprised 25 patients (n=8 Alzheimer's disease (AD); n=3 behavioural variant frontotemporal dementia (bvFTD); n=4 semantic dementia (SD); n=5 progressive non-fluent aphasia (PNFA); n=5 logopenic aphasia (LPA)). The face-to-face patient cohort comprised 64 patients (n=25 AD; n=12 bvFTD; n=9 SD; n=12 PNFA; n=6 LPA). Ten controls who previously participated in face-to-face research also took part remotely. OUTCOME MEASURES: The outcome measures comprised the strength of evidence under a Bayesian framework for differences in performances between testing environments on general neuropsychological and neurolinguistic measures. RESULTS: There was substantial evidence suggesting no difference across environments in both the healthy control and combined patient cohorts (including measures of working memory, single-word comprehension, arithmetic and naming; Bayes Factors (BF)01 >3), in the healthy control group alone (including measures of letter/category fluency, semantic knowledge and bisyllabic word repetition; all BF01 >3), and in the combined patient cohort alone (including measures of working memory, episodic memory, short-term verbal memory, visual perception, non-word reading, sentence comprehension and bisyllabic/trisyllabic word repetition; all BF01 >3). In the control cohort alone, there was substantial evidence in support of a difference across environments for tests of visual perception (BF01=0.0404) and monosyllabic word repetition (BF01=0.0487). CONCLUSIONS: Our findings suggest that remote delivery of neuropsychological tests for dementia research is feasible.

A Pilot Study of Whole-Brain Low-Intensity Pulsed Ultrasound Therapy for Early Stage of Alzheimer's Disease (LIPUS-AD): A Randomized, Double-Blind, Placebo-Controlled Trial.

The prevalence of Alzheimer's disease (AD) has been rapidly increasing worldwide. We have developed a novel angiogenic therapy with low-intensity pulsed ultrasound (LIPUS), which is effective and safe in animal models of AD and vascular dementia. We performed two trials of LIPUS therapy for AD (mild cognitive impairment due to AD and mild AD); a roll-in open trial for safety, and a randomized, double-blind, placebo-controlled (RCT) trial for efficacy and safety. The LIPUS therapy was performed for whole brain through the bilateral temporal bones for one hour 3 times a week as one session under the special conditions (1.3 MPa, 32 cycles, 5% duty cycle) we identified. The LIPUS therapy was performed for one session in the roll-in trial, and 6 sessions in the RCT trial with 3-month intervals for 1.5 years. The primary endpoint was ADAS-J cog scores. The RCT trial was terminated prematurely due to the COVID-19 pandemic. In the roll-in trial (N = 5), no adverse effects were noted. In the RCT trial (N = 22), the worsening of ADAS-J cog scores tended to be suppressed in the LIPUS group compared with the placebo group at week 72 (P = 0.257). When responders were defined as those with no worsening of ADAS-J cog scores at week 72, the prevalence was 50% (5/10) and 0% (0/5) in the LIPUS and placebo groups, respectively (P = 0.053). No adverse effects were noted. These results suggest that the LIPUS therapy is safe and tends to suppress cognitive impairment although a next pivotal trial with a large number of subjects is warranted.

The psychosocial health, experiences and needs of older adults and care partners during the first surge of the COVID-19 pandemic: a mixed-methods study.

BACKGROUND: Minimal research has leveraged qualitative data methods to gain a better understanding of the experiences and needs of older adults (OAs) and care partners of OAs with and without Alzheimer's Disease (AD) and AD-related dementias (AD/ADRD) during the first surge of the COVID-19 pandemic. In this study, we: 1) quantitatively evaluated the psychosocial health of community-dwelling OAs; 2) quantitatively evaluated the perceived stress of care partners for OAs; 3) qualitatively characterized the experiences and needs of community-dwelling OAs and their care partners; and 4) explored differences in the experiences of care partners of OAs with and without AD/ADRD during the first surge of the COVID-19 pandemic in the New York metropolitan area. METHODS: In this mixed-methods study, telephone interviews were conducted with 26 OAs and 29 care partners (16 of whom cared for OAs with AD/ADRD) from April to July 2020. Quantitative data included: demographics; clinical characteristics (Katz Index of independence in activities of daily living (Katz ADL) and the Lawton-Brody instrumental activities of daily living scale (Lawton-Brody)); and psychosocial health: stress was assessed via the Perceived Stress Scale (PSS), social isolation via the Lubben Social Network Scale (LSNS), loneliness via the DeJong Loneliness Scale (DeJong), and depression and anxiety via the Patient Health Questionnaire-Anxiety and Depression (PHQ). Qualitative questions focused on uncovering the experiences and needs of OAs and their care partners. RESULTS: OAs (N = 26) were mostly female (57.7%), and White (76.9%), average age of 81.42 years. While OAs were independent (M = 5.60, Katz ADL) and highly functional (M = 6.92, Lawton-Brody), and expressed low levels of loneliness, stress, depression and anxiety (M = 1.95 on DeJong; M = 12.67 on PSS; M = 1.05 on PHQ depression; and M = 1.09 on PHQ anxiety), open-ended questions elicited themes of fear and worry. Care partners (N = 29) were mostly female (75.9%), White (72.4%), and married (72.4%), and reported moderate stress (M = 16.52 on the PSS), as well as a psychological impact of the pandemic. CONCLUSIONS: Early in the pandemic, OAs reported minimal stress and loneliness; this may have been related to their reports of frequent interaction with family, even if only virtually. By contrast, care partners were moderately stressed and worried, potentially more than usual due to the additional challenges they face when trying to meet their loved ones' needs during a pandemic.

Now is the Time to Improve Cognitive Screening and Assessment for Clinical and Research Advancement.

Wang et al. analyze Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment accuracy as screening tests for detecting dementia associated with Alzheimer's disease (AD). Such tests are at the center of controversy regarding recognition and treatment of AD. The continued widespread use of tools such as MMSE (1975) underscores the failure of advancing cognitive screening and assessment, which has hampered the development and evaluation of AD treatments. It is time to employ readily available, efficient computerized measures for population/mass screening, clinical assessment of dementia progression, and accurate determination of approaches for prevention and treatment of AD and related conditions.

Addressing Suicide Risk in Patients Living With Dementia During the COVID-19 Pandemic and Beyond.

Alzheimer's disease and related dementias (ADRD) are progressive illnesses characterized by decline in cognitive function that impairs performing daily activities. People with ADRD are at an increased risk of suicide, especially those who have comorbid mental health conditions, have specific types of ADRD, or have been recently diagnosed. The coronavirus disease 2019 (COVID-19) pandemic has increased the distress of people with ADRD, a population also at increased risk of contracting the COVID-19 virus. In this article, we draw on a case study and use the Interpersonal Theory of Suicide to help describe the association between ADRD and suicide risk. Secondly, we call for new strategies to mitigate suicide risk in people living with ADRD during and beyond the current pandemic by using lessons learned from cancer care. Our goal is not to dictate solutions but rather to start the conversation by outlining a framework for future research aimed at preventing death by suicide in people with ADRD. Specifically, we draw on the updated Framework for Developing and Evaluating Complex Interventions to reflect on the complexity of the issue and to break it down into achievable parts to reduce the risk of suicidal behavior (ideation, plans, attempts) in those living with ADRD.

Relationship of sex differences in cortical thickness and memory among cognitively healthy subjects and individuals with mild cognitive impairment and Alzheimer disease.

BACKGROUND: An aging society has increased rates of late onset Alzheimer disease dementia (ADD), the most common form of age-related dementia. This neurodegenerative disease disproportionately affects women. METHODS: We use data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) to examine sex differences in cortical thickness (CT) and memory performance. Analyses of covariance (ANCOVA) models were used to examine effects of sex and diagnosis (DX) on CT and verbal memory. For regions demonstrating significant interaction effects of sex and DX, we tested whether sex moderated cognition-thickness relationships. We used machine learning as a complementary method to explore multivariate CT differences between women and men. RESULTS: Women demonstrated greater CT in many brain regions. More specifically, men showed relatively consistent CT declines in all stages, from normal control (NC) to ADD in the bilateral cingulate cortex, bilateral temporal regions, and left precuneus; women had more stable CT in these regions between NC and mild cognitive impairment (MCI) stages, but sharper declines from MCI to ADD. Similarly, for the Rey Auditory Verbal Learning Test (RAVLT), ANCOVA analyses showed that women had significantly better immediate and delayed recall scores than men, at NC and MCI stages, but greater differences, cross-sectionally, from MCI to ADD than men. We found significant sex moderation effects between RAVLT-immediate scores and CT of right isthmus-cingulate for all subjects across DX. Partial correlation analyses revealed that increased CT of right isthmus-cingulate was associated with better verbal learning in women, driven by positron emission tomography defined amyloid positive (Aß+) subjects. Significant sex-moderation effects in cognition-thickness relationships were further found in the right middle-temporal, left precuneus, and left superior temporal regions in Aß+ subjects. Using a machine learning approach, we investigated multivariate CT differences between women and men, showing an accuracy in classification of 75% for Aß+ cognitively NC participants. CONCLUSIONS: Sex differences in memory and CT can play a key role in the different vulnerability and progression of ADD in women compared to men. Machine learning indicates sex differences in CT are most relevant early in the ADD neurodegeneration.

The Sars-Cov-2 Pandemic and the Brave New Digital World of Environmental Enrichment to Prevent Brain Aging and Cognitive Decline.

Individuals experiencing brain aging, cognitive decline, and dementia are currently confronted with several more complex challenges due to the current Sars-Cov-2 pandemic as compared to younger and cognitively healthy people. During the first six months of the pandemic, we are experiencing critical issues related to the management of mild cognitive impairment (MCI) and dementia. The evolving, highly contagious global viral spread has created a pressure test of unprecedented proportions for the existing brain health care infrastructure and related services for management, diagnosis, treatment, and prevention. Social distancing and lock-down measures are catalyzing and accelerating a technological paradigm shift, away from a traditional model of brain healthcare focused on late symptomatic disease stages and towards optimized preventive strategies to slow brain aging and increase resilience at preclinical asymptomatic stages. Digital technologies transform global healthcare for accessible equality of opportunities in order to generate better outcomes for brain aging aligned with the paradigm of preventive medicine.

Higher Depression of Patients with Alzheimer's Disease During than Before the Lockdown.

We assessed depression in 72 patients with Alzheimer's disease (AD) who live in retirement homes during the COVID-19-related lockdown. We invited caregivers of 72 patients with AD who live in retirement homes to rate depression in the patients both before and during the lockdown. Analysis demonstrated increased depression in the patients during the lockdown. We attribute this increased depression to the restrictive measures on activities, visits, and physical contact between patients with AD and family members during the lockdown.

Dementia and COVID-19, a Bidirectional Liaison: Risk Factors, Biomarkers, and Optimal Health Care.

Cognitive impairment following SARS-CoV-2 infection is being increasingly recognized as an acute and possibly also long-term sequela of the disease. Direct viral entry as well as systemic mechanisms such as cytokine storm are thought to contribute to neuroinflammation in these patients. Biomarkers of COVID-19-induced cognitive impairment are currently lacking, but there is some limited evidence that SARS-CoV-2 could preferentially target the frontal lobes, as suggested by behavioral and dysexecutive symptoms, fronto-temporal hypoperfusion on MRI, EEG slowing in frontal regions, and frontal hypometabolism on 18F-FDG-PET. Possible confounders include cognitive impairment due to hypoxia and mechanical ventilation and post-traumatic stress disorder. Conversely, patients already suffering from dementia, as well as their caregivers, have been greatly impacted by the disruption of their care caused by COVID-19. Patients with dementia have experienced worsening of cognitive, behavioral, and psychological symptoms, and the rate of COVID-19-related deaths is disproportionately high among cognitively impaired people. Multiple factors, such as difficulties in remembering and executing safeguarding procedures, age, comorbidities, residing in care homes, and poorer access to hospital standard of care play a role in the increased morbidity and mortality. Non-pharmacological interventions and new technologies have shown a potential for the management of patients with dementia, and for the support of their caregivers.

The Impact of a Global Pandemic on People Living with Dementia and Their Care Partners: Analysis of 417 Lived Experience Reports.

BACKGROUND: The COVID-19 pandemic is impacting the physical and emotional health of older adults living with dementia and their care partners. OBJECTIVE: Using a patient-centered approach, we explored the experiences and needs of people living with dementia and their care partners during the COVID-19 pandemic as part of an ongoing evaluation of dementia support services in British Columbia, Canada. METHODS: A survey instrument was developed around the priorities identified in the context of the COVID-19 and Dementia Task Force convened by the Alzheimer Society of Canada. RESULTS: A total of 417 surveys were analyzed. Overall, respondents were able to access information that was helpful for maintaining their own health and managing a period of social distancing. Care partners reported a number of serious concerns, including the inability to visit the person that they care for in long-term or palliative care. Participants also reported that the pandemic increased their levels of stress overall and that they felt lonelier and more isolated than they did before the pandemic. The use of technology was reported as a way to connect socially with their loved ones, with the majority of participants connecting with others at least twice per week. CONCLUSION: Looking at the complex effects of a global pandemic through the experiences of people living with dementia and their care partners is vital to inform healthcare priorities to restore their quality of life and health and better prepare for the future.

Needs of Dementia Family Caregivers in Spain During the COVID-19 Pandemic.

We explored the experience from caregivers of people with dementia (PwD) during mandatory confinement due to the COVID-19 pandemic in Spain. An online survey, which studied the perceptions of the main problems and consequences experienced during confinement, was answered by 106 family caregivers of PwD. Results showed that family caregivers of PwD experienced psychological problems, like anxiety, mood, sleep, or eating disorders during confinement and felt less supported when they had to handle challenging behaviors or offer meaningful activities. An innovative multi-tiered supportive approach is needed which considers a post-pandemic reality and ensures the continuity of quality care for PwD and their family careers.

Effects of COVID-19 Home Confinement on Mental Health in Individuals with Increased Risk of Alzheimer's Disease.

We explored the impact of the Spanish COVID-19 strict home confinement on mental health and cognition in non-infected subjects (N = 16, 60-80 years) diagnosed with subjective cognitive decline and APOEɛ3/ɛ4 carriers. Mental health was monitored for 2 months on a daily, weekly, or monthly basis, and compared to pre-confinement values. Emotional distress, anxiety, and depression scores increased to pathological threshold values during and after confinement. Those with lower mood during confinement experienced a decline in their mood after confinement. Cognition did not change. These preliminary results suggest that mental health consequences of corona measures in preclinical stages of Alzheimer's disease should be further evaluated.

Implementing Delirium Prevention in the Era of COVID-19.

Patients admitted with COVID-19 can develop delirium due to predisposing factors, isolation, and the illness itself. Standard delirium prevention methods focus on interaction and stimulation. It can be challenging to deliver these methods of care in COVID settings where it is necessary to increase patient isolation. This paper presents a typical clinical vignette of representative patients in a tertiary care hospital and how a medical team modified an evidence-based delirium prevention model to deliver high-quality care to COVID-19 patients. The implemented model focuses on four areas of delirium-prevention: Mobility, Sleep, Cognitive Stimulation, and Nutrition. Future studies will be needed to track quantitative outcome measures.

Alzheimer's Disease and Face Masks in Times of COVID-19.

Generalized lockdown caused by COVID-19, necessary yesterday, can no longer be that of tomorrow. It will no longer be possible to cram the humblest into cramped areas, but priority must be given to prevention (certainly with physical barriers, hydro-alcoholic gel, face masks), biological diagnosis, isolation, and also the care of any infected person. COVID-19 has hit the most vulnerable first in terms of biological inequality, such as Alzheimer's disease (AD) patients. Those with AD can have sensorial deficits and perception troubles, including visual difficulties and the inability to recognize faces and emotions. Face masks and physical distancing can disrupt facial familiarity and make it more difficult to recognize emotional facial expressions. It can provoke distress, which the visitor can perceive and feel obligated to take off the face mask. This gesture should not be considered as an act of indiscipline, but an act of empathy. Transparent face masks could improve the suffering of AD patients, distraught in the presence of their loved ones whose masks hide their faces. Wearing a mask should not be due to fear of punishment, but as an understanding of the responsibility of each individual in the control of the current pandemic. It may be necessary to convince more citizens of this civic duty, using clear and attractive messaging in order to standardize the wearing of face masks for the general public and to adapt them to the needs of patients.

Calcium Channel Blockers: A Possible Potential Therapeutic Strategy for the Treatment of Alzheimer's Dementia Patients with SARS-CoV-2 Infection.

Studies have shown that the calcium ion (Ca2+) plays important roles both in Alzheimer's dementia and SARS-CoV S-mediated fusion to host cell entry. An elevated level of intracellular calcium causes neuronal dysfunction, cell death, and apoptosis. Dysregulation of calcium has also been shown to increase the production of amyloid beta (Aß) protein, the hallmark of Alzheimer's dementia. Reversely, deposition of Aß is also responsible for calcium dysregulation. On the other hand, it has been well investigated that viruses can disturb host cell Ca2+ homeostasis as well as modulate signal transduction mechanisms. Viruses can also hijack the host cell calcium channels and pumps to release more intracellular Ca2+ to utilize for their life cycle. Even though evidence has not been reported on SARS-CoV-2 concerning Ca2+ regulation, however, it has been well established that Ca2+ is essential for viral entry, viral gene replication, and virion maturation and release. Recent reports suggest that SARS-CoV needs two Ca2+ ions to fuse with the host cell at the entry step. Furthermore, some calcium channel blockers (CCBs), such as nimodipine, memantine, etc., have been reported to be effective in the treatment of dementia in Alzheimer's disease (AD) as well as have shown inhibition in various virus infections.

High depression and anxiety in people with Alzheimer's disease living in retirement homes during the covid-19 crisis.

To cope with Covid-19 and limits its spread among residents, retirement homes have prohibited physical contact between residents and families and friend and, in some cases, even between residents or between residents and caregivers. We investigated the effects of measures against Covid-19 on the mental health of participants with Alzheimer's disease (AD) who live in retirement homes in France. We instructed on-site caregivers to assess depression and anxiety in participants with mild AD who live in retirement homes. Fifty-eight participants consented to participate in the study. The participants rated their depression and anxiety during and before the Covid-19 crisis. Participants reported higher depression (p = .005) and anxiety (p = .004) during than before the Covid-19 crisis. These increases can be attributed to the isolation of the residents and/or to the drastic changes in their daily life and care they receive. While, in their effort to prevent infections, retirement homes are forced to physically separate residents from the outside world and to drastically reduce residents' activities, these decisions are likely to come at a cost to residents with AD and their mental health.

Awareness of the COVID-19 Outbreak and Resultant Depressive Tendencies in Patients with Severe Alzheimer's Disease.

The ongoing coronavirus disease 2019 (COVID-19) pandemic has substantially affected patients with dementia and their caregivers. However, we found not all Alzheimer's disease (AD) patients were afraid of COVID-19 infection. Therefore, we investigated the association between rate of awareness of COVID-19 and depressive tendency in AD. 126 consecutive outpatients with AD were enrolled in this study from May 25, on the day when the declaration of emergency was lifted in Japan, through June 30, 2020. In addition to routine psychological tests, the participants were asked the following two questions: "Do you know COVID-19?" and "Why are you wearing a face mask?". Moderate to severe AD patients were found to have a low COVID-19 recognition rate and did not fully understand why they were wearing face masks. In addition, because they did not understand the seriousness of the COVID-19 outbreak, their Geriatric Depression Scale scores were also substantially lower. These results may appear to simply indicate that people with severe dementia are unaware of current events. However, these results provide insights into how to care for patients with dementia and how to allocate the time and support of our limited staff during the COVID-19 outbreak.