Background: The sudden and drastic changes due to the Coronavirus Disease 19 (COVID-19) pandemic have impacted people's physical and mental health. Clinically-vulnerable older people are more susceptible to severe effects either directly by the COVID-19 infection or indirectly due to stringent social isolation measures. Social isolation and loneliness negatively impact mental health in older adults and may predispose to cognitive decline. People with cognitive impairments may also be at high risk of worsening cognitive and mental health due to the current pandemic. This review provides a summary of the recent literature on the consequences of COVID-19, due to either viral infection or social isolation, on neuropsychiatric symptoms in older adults with and without dementia. Methods: A search was conducted in PubMed and Web of Science to identify all relevant papers published up to the 7th July 2020. Two independent assessors screened and selected the papers suitable for inclusion. Additional suitable papers not detected by literature search were manually added. Results: Fifteen articles were included: 8 focussed on the psychiatric symptoms caused by the COVID-19 infection and 7 investigated the impact of social isolation on older adults' neuropsychiatric symptoms. Four studies included older adults without dementia and 11 included patients with cognitive impairment mainly due to Alzheimer's disease. All studies found that different neuropsychiatric symptoms emerged and/or worsened in older adults with and without dementia. These changes were observed as the consequence of both COVID-19 infection and of the enforced prolonged conditions of social isolation. Cases were reported of viral infection manifesting with delirium at onset in the absence of other symptoms. Delirium, agitation and apathy were the symptoms most commonly detected, especially in people with dementia. Conclusion: The available evidence suggests that the COVID-19 pandemic has a wide negative impact on the mental well-being of older adults with and without dementia. Viral infection and the consequent social isolation to limit its spreading have a range of neuropsychiatric consequences. Larger and more robustly designed studies are needed to clarify such effects and to assess the long-term implications for the mental health of older adults, and to test possible mitigating strategies.

Alzheimer’s disease (AD) is the most common cause of dementia worldwide and is characterised pathologically by the accumulation of amyloid beta and tau protein aggregates. Currently, there are no approved disease modifying therapies for clearance of either of these proteins from the brain of people with AD. As well as abnormalities in protein aggregation, other pathological changes are seen in this condition. The function of mitochondria in both the nervous system and rest of the body is altered early in this disease, and both amyloid and tau have detrimental effects on mitochondrial function. In this review article, we describe how the function and structure of mitochondria change in AD. This review summarises current imaging techniques that use surrogate markers of mitochondrial function in both research and clinical practice, but also how mitochondrial functions such as ATP production, calcium homeostasis, mitophagy and reactive oxygen species production are affected in AD mitochondria. The evidence reviewed suggests that the measurement of mitochondrial function may be developed into a future biomarker for early AD. Further work with larger cohorts of patients is needed before mitochondrial functional biomarkers are ready for clinical use.

Background: There is an urgent need to identify the earliest biological changes within the neuropathological cascade of Alzheimer’s disease (AD) processes. Recent findings in a murine model of AD showed significant preclinical loss of dopaminergic ne

There is emerging evidence suggesting that Alzheimer's disease is a vascular disorder, caused by impaired cerebral perfusion, which may be promoted by cardiovascular risk factors that are strongly influenced by lifestyle. In order to develop an understanding of the exact nature of such a hypothesis, a biomechanical understanding of the influence of lifestyle factors is pursued. An extended poroelastic model of perfused parenchymal tissue coupled with separate workflows concerning subject-specific meshes, permeability tensor maps and cerebral blood flow variability is used. The subject-specific datasets used in the modelling of this paper were collected as part of prospective data collection. Two cases were simulated involving male, non-smokers (control and mild cognitive impairment (MCI) case) during two states of activity (high and low). Results showed a marginally reduced clearance of cerebrospinal fluid (CSF)/interstitial fluid (ISF), elevated parenchymal tissue displacement and CSF/ISF accumulation and drainage in the MCI case. The peak perfusion remained at 8 mm s ⁻¹ between the two cases.

Background: Other than its direct impact on cardiopulmonary health, Coronavirus Disease 2019 (COVID-19) infection affects additional body systems, especially in older adults. Several studies have reported acute neurological symptoms that present at onset or develop during hospitalisation, with associated neural injuries. Whilst the acute neurological phase is widely documented, the long-term consequences of COVID-19 infection on neurocognitive functioning remain unknown. Although an evidence-based framework describing the disease chronic phase is premature, it is important to lay the foundations for future data-driven models. This systematic review aimed at summarising the literature on neuroimaging and neuropathological findings in older over-60 patients with COVID-19 following a cognitive neuroscientific perspective, to clarify the most vulnerable brain areas and speculate on the possible cognitive consequences.Methods: PubMed and Web of Science databases were searched to identify relevant manuscripts published between 1st March 2020 and 31th December 2020. Outputs were screened and selected by two assessors. Relevant studies not detected by literature search were added manually.Results: Ninety studies, mainly single cases and case series, were included. Several neuroimaging and neuropathological findings in older patients with COVID-19 emerged from these studies, with cerebrovascular damage having a prominent role. Abnormalities (hyperintensities, hypoperfusion, inflammation, and cellular damage) were reported in most brain areas. The most consistent cross-aetiology findings were in white matter, brainstem and fronto-temporal areas. Viral DNA was detected mainly in olfactory, orbitofrontal and brainstem areas.Conclusion: Studies on COVID-19 related neural damage are rich and diverse, but limited to description of hospitalised patients with fatal outcome (i.e., in neuropathological studies) or severe symptoms (i.e., in neuroimaging studies). The damage seen in this population indicates acute and largely irreversible dysfunction to neural regions involved in major functional networks that support normal cognitive and behavioural functioning. It is still unknown whether the long-term impact of the virus will be limited to chronic evolution of acute events, whether sub-clinical pathological processes will be exacerbated or whether novel mechanisms will emerge. Based on current literature, future theoretical frameworks describing the long-term impact of COVID-19 infection on mental abilities will have to factor in major trends of aetiological and topographic heterogeneity.