Prefrontal Aβ pathology influencing the pathway from apathy to cognitive decline in non-dementia elderly

Sun, Lin; Li, Wei; Li, Guanjun; Xiao, Shifu; Initiative, Alzheimer’s Disease Neuroimaging

doi:10.1038/s41398-021-01653-8

Cited by 12 publications

(13 citation statements)

References 30 publications

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“…Several neuroanatomical mechanisms are hypothesized to underlie apathy and depression. In elderly individuals without dementia, apathy has been associated with amyloid‐β (Aβ) pathology, indexed by the ratio of Aβ 42 to t‐tau in the cerebrospinal fluid (CSF) and the burden of Aβ as shown by amyloid positron emission tomography (PET) 97 . A vascular contribution has been proposed, where apathy may result from destruction of limbic and reward pathways in the brain associated with small vessel disease (SVD) 98,99 .…”

Section: Distinguishing Apathy and Depression On The Basis Of Neurobi...mentioning

confidence: 99%

“…Reduced cortical thickness in right frontal and temporoparietal regions 118 Increased cortical thickness in right lateral and medial orbitofrontal cortices, right pars orbitalis, and right rostral anterior cingulate 118 White matter networks Larger volumes of frontal white matter hyperintensities 110 Larger volume of white matter hyperintensities in right parietal lobe 110 Reduced white matter connectivity in premotor and cingulate regions 90 ; white matter integrity in temporoparietal regions 89 Not significantly correlated with reduced regional connectivity or white matter integrity 89,90 Hippocampal volume Correlated with lower hippocampal volume 111 No relationship with hippocampal volume 111 PET and fluid biomarkers Frontal Aβ deposition associated with risk of developing apathy 97 ; associated with tau 113 and Aβ 114 deposition in frontal regions Associated with the ratio of Aβ 42 /Aβ 40 in plasma 119 Abbreviation: PET, positron emission tomography.…”

Section: Cortical Thicknessmentioning

confidence: 99%

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Distinguishing apathy from depression: A review differentiating the behavioral, neuroanatomic, and treatment‐related aspects of apathy from depression in neurocognitive disorders

Lanctôt

Ismail

Bawa

et al. 2023

Int J Geriat Psychiatry

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Objectives This narrative review describes the clinical features of apathy and depression in individuals with neurocognitive disorders (NCDs), with the goal of differentiating the two syndromes on the basis of clinical presentation, diagnostic criteria, neuropathological features, and contrasting responses to treatments. Methods Literature was identified using PubMed, with search terms to capture medical conditions of interest; additional references were also included based on our collective experience and knowledge of the literature. Results Evidence from current literature supports the distinction between the two disorders; apathy and depression occur with varying prevalence in individuals with NCDs, pose different risks of progression to dementia, and have distinct, if overlapping, neurobiological underpinnings. Although apathy is a distinct neuropsychiatric syndrome, distinguishing apathy from depression can be challenging, as both conditions may occur concurrently and share several overlapping features. Apathy is associated with unfavorable outcomes, especially those with neurodegenerative etiologies (e.g., Alzheimer's disease) and is associated with an increased burden for both patients and caregivers. Diagnosing apathy is important not only to serve as the basis for appropriate treatment, but also for the development of novel targeted interventions for this condition. Although there are currently no approved pharmacologic treatments for apathy, the research described in this review supports apathy as a distinct neuropsychiatric condition that warrants specific treatments aimed at alleviating patient disability. Conclusions Despite differences between these disorders, both apathy and depression pose significant challenges to patients, their families, and caregivers; better diagnostics are needed to develop more tailored treatment and support.

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Section: Distinguishing Apathy and Depression On The Basis Of Neurobi...mentioning

confidence: 99%

Section: Cortical Thicknessmentioning

confidence: 99%

Distinguishing apathy from depression: A review differentiating the behavioral, neuroanatomic, and treatment‐related aspects of apathy from depression in neurocognitive disorders

Lanctôt

Ismail

Bawa

et al. 2023

Int J Geriat Psychiatry

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“…Overall, the above mentioned clinical studies show that the various functional, structural or metabolic alterations affecting the dopaminergic VTA and its mesocorticolimbic targets since the MCI stage ( Figure 1 , panel B) are a very precocious phenomenon in the disease progression, that can be related with the early appearance of NPS. In fact, today the assessment of CSF biomarkers and the application of the Neuropsychiatric Inventory (NPI) for evaluation of NPS are standard clinical practices, with a strong proven link between the two, such as increased levels of total (t-tau) and phosphorylated tau (p-tau) proteins and low levels of Aβ42 correlating with apathy, anxiety, agitation, and irritability ( 143 – 148 ). Combined with these diagnostic tools, early identification of alterations in the mesocorticolimbic dopamine system could provide an additional valid biomarker aimed at the prognosis of NPS and thus prediction of disease acceleration and faster conversion from MCI to AD.…”

Section: Conclusion: Implications For Early Diagnosis and Treatmentmentioning

confidence: 99%

The VTA dopaminergic system as diagnostic and therapeutical target for Alzheimer's disease

2022

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Neuropsychiatric symptoms (NPS) occur in nearly all patients with Alzheimer's Disease (AD). Most frequently they appear since the mild cognitive impairment (MCI) stage preceding clinical AD, and have a prognostic importance. Unfortunately, these symptoms also worsen the daily functioning of patients, increase caregiver stress and accelerate the disease progression from MCI to AD. Apathy and depression are the most common of these NPS, and much attention has been given in recent years to understand the biological mechanisms related to their appearance in AD. Although for many decades these symptoms have been known to be related to abnormalities of the dopaminergic ventral tegmental area (VTA), a direct association between deficits in the VTA and NPS in AD has never been investigated. Fortunately, this scenario is changing since recent studies using preclinical models of AD, and clinical studies in MCI and AD patients demonstrated a number of functional, structural and metabolic alterations affecting the VTA dopaminergic neurons and their mesocorticolimbic targets. These findings appear early, since the MCI stage, and seem to correlate with the appearance of NPS. Here, we provide an overview of the recent evidence directly linking the dopaminergic VTA with NPS in AD and propose a setting in which the precocious identification of dopaminergic deficits can be a helpful biomarker for early diagnosis. In this scenario, treatments of patients with dopaminergic drugs might slow down the disease progression and delay the impairment of daily living activities.

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“… Johansson et al [ 110 ] (18)F-flutemetamol-PET sMRI, FreeSurfer T2 FLAIR for white matter lesions (WML), LST toolbox AES CN ( n = 104), MCI ( n = 53) followed for up to 4 years Apathy and anxiety were shown related to Aβ deposition and predicted cognitive decline. Apathy level, but not anxiety, was associated with atrophy in the ACC, PCC, lateral temporal, and parietal cortex, as well as white matter lesion volume Sun et al [ 111 ] Aβ PET, ROI - medial orbitofrontal cortex (mOFC) and the pars orbitalis cortex (POFC). NPI non-demented apathy(+) n = 114, among which 78 with Aβ PET, non-demented apathy (-) n = 943, among which 569 with Aβ PET, 5–6 year follow-up (ADNI data) Individuals with apathy, higher CSF Aβ42 level, or frontal lobe Aβ deposition had an increased risk of cognitive decline compared with those without apathy.…”

Section: Introductionmentioning

confidence: 99%

The neurobiology of apathy in depression and neurocognitive impairment in older adults: a review of epidemiological, clinical, neuropsychological and biological research

et al. 2022

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Apathy is a common condition that involves diminished initiative, diminished interest and diminished emotional expression or responsiveness. It is highly prevalent in the context of a variety of neuropsychiatric disorders and is related to poor health outcomes. Presence of apathy is associated with cognitive and functional decline in dementia. Despite its negative impact on health, there is no definitive treatment for apathy, a clinical reality that may be due in part to lack of knowledge about assessment, neuropsychological features and neurobiological underpinnings. Here, we review and synthesize evidence from clinical, epidemiological, neuropsychological, peripheral biomarker and neuroimaging research. Apathy is a common feature of depression and cognitive disorders and is associated with impairment in executive function. Neuropsychological and neuroimaging studies point to dysfunction of brain circuitry involving the prefrontal cortex, especially the dorsolateral prefrontal cortex circuit, the dorsomedial prefrontal cortex circuit, and the ventromedial prefrontal cortex circuit. However, inconsistent findings, particularly in neuroimaging may be due to heterogeneity of apathy symptoms (with a need to better elucidate subtypes), neuropsychiatric comorbidities, the severity of cognitive impairment and other factors. These factors need to be accounted for in future studies so that biomarker research can make progress. On the whole, the literature on apathy has identified likely neurocognitive, peripheral biomarker and neuroimaging targets for understanding apathy, but also points to the need to address methodological issues that will better inform future studies. In turn, as we learn more about the underpinning of apathy and its subtypes, subsequent research can focus on new neurally based interventions that will strengthen the clinical management of apathy in the context of its comorbidities.

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Prefrontal Aβ pathology influencing the pathway from apathy to cognitive decline in non-dementia elderly

Cited by 12 publications

References 30 publications

Distinguishing apathy from depression: A review differentiating the behavioral, neuroanatomic, and treatment‐related aspects of apathy from depression in neurocognitive disorders

Distinguishing apathy from depression: A review differentiating the behavioral, neuroanatomic, and treatment‐related aspects of apathy from depression in neurocognitive disorders

The VTA dopaminergic system as diagnostic and therapeutical target for Alzheimer's disease

The neurobiology of apathy in depression and neurocognitive impairment in older adults: a review of epidemiological, clinical, neuropsychological and biological research

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