Altered frontal and insular functional connectivity as pivotal mechanisms for apathy in Alzheimer's disease

Jones, Sarah; Marco, Matteo De; Manca, Riccardo; Bell, Simon M; Blackburn, Daniel; Wilkinson, Iain D.; Soininen, Hilkka; Venneri, Annalena

doi:10.1016/j.cortex.2019.04.008

Cited by 31 publications

(27 citation statements)

References 57 publications

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“…Although any mechanistic hypothesis would be, at this stage, speculative, it is of central importance to shed light on the map of regional brain damage caused by the virus, because the topography of network dysfunction may account for the onset of chronic behavioural symptoms. A number of studies has shown that the presence of psychiatric symptoms in patients with AD is associated with alterations of brain circuitry (37)(38)(39). If COVID-19 infection damages the neural tissue, it might result into an impoverishment of the neural pathways that support normal psychological functioning and could lead to the onset of cognitive and/or psychiatric dysfunction.…”

Section: Neuropsychiatric Symptoms In People Who Have Contracted Covimentioning

confidence: 99%

The Impact of COVID-19 Infection and Enforced Prolonged Social Isolation on Neuropsychiatric Symptoms in Older Adults With and Without Dementia: A Review

2020

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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. Manca et al. Ageing and COVID-19 Neuropsychiatric Complications 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.

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Section: Neuropsychiatric Symptoms In People Who Have Contracted Covimentioning

confidence: 99%

The Impact of COVID-19 Infection and Enforced Prolonged Social Isolation on Neuropsychiatric Symptoms in Older Adults With and Without Dementia: A Review

2020

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“…We used binary NPI scores (symptom present when score >0) similar to other authors (e.g. Jones et al, 2019) as thresholds of clinical significance may vary by symptom (Cummings et al, 1994), and as the nonlinear and skewed frequency × severity score distributions may be problematic in some statistical analyses (Lai, 2014). NPI scores (range 0-144) for each annual measurement can be seen in Table 1.…”

Section: Assessment Of Npssmentioning

confidence: 99%

“…Furthermore, the NPI frequency × severity score requires nonparametric statistical methods (Lai, 2014). Therefore, many authors (recently, e.g., Jones et al, 2019) prefer to use the binary NPI score avoid these issues. Most importantly, individual symptom data are obfuscated when using this compound score.…”

Section: Limitationsmentioning

confidence: 99%

Neuropsychiatric symptoms and activities of daily living in Alzheimer’s disease: ALSOVA 5-year follow-up study

Saari

Hallikainen

Hintsa

et al. 2019

Int. Psychogeriatr.

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ABSTRACTBackground:Neuropsychiatric symptoms (NPSs) in Alzheimer’s disease (AD) are related to activities of daily living (ADLs), but longitudinal studies are sparse.Objectives:We investigated which NPSs were related to decline in instrumental ADLs (IADLs) and basic ADLs (BADLs) in a 5-year follow-up of individuals with AD.Methods:ALSOVA 5-year follow-up study data of 236 individuals with very mild or mild AD at baseline and their caregiver were analyzed. IADLs and BADLs were assessed with Alzheimer’s Disease Cooperative Study ADL inventory, and NPSs with Neuropsychiatric Inventory at annual follow-up visits. Generalized estimating equations (GEEs) were used for longitudinal data analysis, and NPS–ADL networks were estimated to demonstrate symptom interactions.Results:Apathy [rate ratio (RR) 1.23, 95% CI 1.06–1.44, p = 0.007], aberrant motor behavior (RR 1.24, 95% CI 1.07–1.44, p = 0.005), and appetite disturbances (RR 1.22, 95% CI 1.06–1.41, p = 0.005) were related to impairment in BADLs, and the same symptoms (RR 1.13, 95% CI 1.07–1.21, p < 0.001; RR 1.13, 95% CI 1.07–1.20, p < 0.001; RR 1.14; 95% CI 1.08–1.21, p < 0.001, for apathy, aberrant motor behavior, and appetite disturbances, respectively), in addition to delusions (RR 1.09, 95% CI 1.03–1.15, p = 0.004), were related to IADL impairment. Symptom networks varied at different time points.Conclusion:As AD progresses, common (apathy) and uncommon NPSs (aberrant motor behavior, appetite disturbances, delusions) seem to be related to ADLs through various symptom interactions. Previous literature suggests that frontal pathology could underlie these relationships.

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“…Neuroimaging studies of apathy have predominantly focused on individuals with brain diseases or psychiatric conditions, including stroke (Kang and Kim, 2008;Onoda et al, 2011;Rochat et al, 2013;Kumral et al, 2019), neurodegeneration (Apostolova et al, 2007;Marshall et al, 2007;Reijnders et al, 2010;Tunnard et al, 2011;Eslinger et al, 2012;Carriere et al, 2014;Jones et al, 2019), and late-life depression (Lavretsky et al, 2007;Alexopoulos et al, 2013;Yuen et al, 2014). Reviews integrating structural and functional correlates of apathy across different disorders have identified regions commonly associated with apathy, including the anterior cingulate cortex (ACC), ventral striatum (nucleus accumbens; NAcc), thalamus, orbitofrontal cortex (OFC), and insula (IC) (Kos et al, 2016;Le Heron et al, 2018;Pimontel et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Resting-State Functional Connectivity Signatures of Apathy in Community-Living Older Adults

Jang

Han

Yew

et al. 2021

Front. Aging Neurosci.

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Apathy predicts poor outcomes in older adults, and its underlying neural mechanism needs further investigation. We examined the association between symptoms of apathy and functional connectivity (FC) in older adults without stroke or dementia. Participants included 48 individuals (mean age = 70.90) living independently in the community, who underwent resting-state fMRI and completed the Apathy Evaluation Scale (AES). Seed-to-voxel analysis (cluster-level p-FDR <0.05, voxel threshold p < 0.001) tested the association between AES scores and the whole-brain FC of brain regions involved in reward- and salience-related processing. We found that AES scores were negatively associated with FC of the right insula cortex and right anterior temporal regions (124 voxels, t = −5.10) and FC of the left orbitofrontal cortex and anterior cingulate regions (160 voxels, t = −5.45), and were positively associated with FC of the left orbitofrontal cortex and left lateral prefrontal (282 voxels, t = 4.99) and anterior prefrontal (123 voxels, t = 4.52) regions. These findings suggest that apathy in older adults may reflect disruptions in neural connectivity involved in reward- and salience-related processing.

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Altered frontal and insular functional connectivity as pivotal mechanisms for apathy in Alzheimer's disease

Cited by 31 publications

References 57 publications

The Impact of COVID-19 Infection and Enforced Prolonged Social Isolation on Neuropsychiatric Symptoms in Older Adults With and Without Dementia: A Review

The Impact of COVID-19 Infection and Enforced Prolonged Social Isolation on Neuropsychiatric Symptoms in Older Adults With and Without Dementia: A Review

Neuropsychiatric symptoms and activities of daily living in Alzheimer’s disease: ALSOVA 5-year follow-up study

Resting-State Functional Connectivity Signatures of Apathy in Community-Living Older Adults

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