Alzheimer's disease biomarkers as predictors of trajectories of depression and apathy in cognitively normal individuals, mild cognitive impairment<scp>,</scp> and Alzheimer's disease dementia

Banning, Leonie C.P.; Ramakers, Inez H.G.B.; Rosenberg, Paul B.; Leoutsakos, Jeannie Marie S.; Initiative, Alzheimer’s Disease Neuroimaging

doi:10.1002/gps.5418

Cited by 27 publications

(38 citation statements)

References 35 publications

(44 reference statements)

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“…Apathy and depression frequently coexist in dementia, however either can occur without the other, so they are generally regarded as separate entities, a view supported by biomarker evidence [ 6 ]. The presence of apathy is associated with less favourable outcomes in dementia, including more rapid functional and cognitive decline [ 7 ], greater disease severity [ 8 ], and increased mortality [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

The Experience of Apathy in Dementia: A Qualitative Study

Baber

Chang

Yates

et al. 2021

IJERPH

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We aimed to explore and gain an understanding into how people with dementia experience apathy, and consequently suggest effective interventions to help them and their carers. Twelve participants (6 dyads of 6 people with dementia and their family carers) were recruited from “memory cafes” (meeting groups for people with dementia and their families), social groups, seminars, and patient and public involvement (PPI) meetings. People with dementia and their carers were interviewed separately and simultaneously. Quantitative data were collected using validated scales for apathy, cognition, anxiety, and depression. The interviews were semi-structured, focusing on the subjective interpretation of apathy and impacts on behaviour, habits, hobbies, relationships, mood, and activities of daily living. Interviews were recorded and transcribed. Transcripts were analysed using interpretative phenomenological analysis (IPA), which generated codes and patterns that were collated into themes. Four major themes were identified, three of which highlighted the challenging aspects of apathy. One described the positive aspects of the individuals’ efforts to overcome apathy and remain connected with the world and people around them. This study is the first to illustrate the subjective experience of apathy in dementia, portraying it as a more complex and active phenomenon than previously assumed. Apathy and its effects warrant more attention from clinicians, researchers, and others involved in dementia care.

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Section: Introductionmentioning

confidence: 99%

The Experience of Apathy in Dementia: A Qualitative Study

Baber

Chang

Yates

et al. 2021

IJERPH

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“…Moreover, amyloid pathology was found to play a mediation role in associating minimal depressive symptoms with cognitive impairments in the non-dementia population [ 31 ]. Lower Aβ 42 and higher p-tau were also confirmed to be related to an increased probability of depression and apathy over time [ 32 ]. There was an overlap between apathy and depression, which shared common clinical features in AD.…”

Section: Discussionmentioning

confidence: 99%

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

Sun

et al. 2021

Transl Psychiatry

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The purpose of this study is to investigate the complex connection between apathy and cognitive decline that remains unclear. A total of 1057 non-dementia elderly from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database received up to 13 years of follow-up and were divided into an apathy negative (−) group of 943 participants and an apathy positive (+) group of 114 participants through the Neuropsychiatric Inventory (NPI)-apathy subitem. Cerebrospinal fluid (CSF) AD biomarkers and amyloid β (Aβ) PET were measured, and their longitudinal changes were assessed using linear mixed-effects models. Risk factors for cognitive decline and apathy conversion were explored through the Cox proportional hazards model. Mediation effects of Aβ pathology on cognition were investigated using the causal mediation analysis. Apathy syndrome was associated with faster impairment of cognition and elevation of the Aβ burden. The effects of apathy on cognitive function and life quality were mediated by Aβ pathology, including CSF Aβ42/total tau ratio, and Aβ deposition in the prefrontal regions. Apathy syndrome was the risk factor for cognitive deterioration; meanwhile, frontal Aβ burden was the risk factor for apathy conversion. Apathy syndrome is an early manifestation of cognitive decline and there are bidirectional roles between apathy syndrome and Aβ pathology. Prefrontal Aβ pathology influenced the pathway from apathy to cognitive decline.

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“…While previous work identi ed unique trajectories of depression and apathy in LOAD subjects and biomarkers associated with LOAD-speci c depression progression 5 , the current work focused on a genetic based prediction model of depression in LOAD. Collectively, our approach generated PRS to identify LOAD subjects with greater genetic risk of developing depression and those at risk to develop depression earlier in the time course of LOAD.…”

Section: Discussionmentioning

confidence: 99%

“…Neuropsychiatric symptoms (NPS) are common in Late-onset Alzheimer's Disease (LOAD), characterized by heterogeneity with highly variable onset duration and severity. Amongst LOAD with comorbid NPS, depression and anxiety are the most prevalent [1][2][3][4][5] . Furthermore, individuals with depression are at greater risk to develop LOAD, suggesting that treating depression may delay LOAD 2,6 .…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, individuals with depression are at greater risk to develop LOAD, suggesting that treating depression may delay LOAD 2,6 . In addition, distinct trajectories of increasing risk of depression were associated with LOAD pathology such as, lower cerebrospinal uid (CSF) Aβ 42 and higher CSF total and phosphorylated tau, highlighting the heterogeneity of depression within LOAD 5 . Interestingly, we previously identi ed shared genetic etiology between LOAD and major depressive disorder (MDD) 6 .…”

Section: Introductionmentioning

confidence: 99%

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Polygenic Risk Score Effectively Predicts Risk of Depression Onset in Alzheimer’s Disease

Upadhya

Liu

Luo

et al. 2021

Preprint

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Introduction: Depression is a common, though heterogenous, comorbidity in late-onset Alzheimer’s Disease (LOAD) patients. In addition, individuals with depression are at greater risk to develop LOAD. In previous work, we demonstrated shared genetic etiology between depression and LOAD. Collectively, this evidence suggested interactions between depression and LOAD. However, the underpinning genetic heterogeneity of depression co-occurrence with LOAD is largely unknown.Methods: Major Depressive Disorder (MDD) genome wide association study (GWAS) summary statistics were used to create polygenic risk scores (PRS). The Religious Orders Society and Rush Memory and Aging Project (ROSMAP) and National Alzheimer’s Coordinating Center (NACC) datasets were utilized to assess the PRS performance in predicting depression onset in LOAD patients.Results: The developed PRS showed marginal results in standalone models for predicting depression onset in both ROSMAP (AUC=0.540) and NACC (AUC=0.534). Full models, with baseline age, sex, education, and APOEε4 allele count, showed improved prediction of depression onset (ROSMAP AUC: 0.606, NACC AUC: 0.583). In time-to-event analysis, standalone PRS models showed significant effects in ROSMAP (P=0.0051), but not in NACC cohort. Full models showed significant performance in predicting depression in LOAD for both datasets (P<0.001 for all).Discussion: This study provided new insights into the genetic factors contributing to depression onset in LOAD and advanced our knowledge of the genetics underlying the heterogeneity of depression in LOAD. The developed PRS accurately predicted LOAD patients with depressive symptoms, thus, has clinical implications including, diagnosis of LOAD patients at high-risk to develop depression for early anti-depressant treatment.

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Alzheimer's disease biomarkers as predictors of trajectories of depression and apathy in cognitively normal individuals, mild cognitive impairment, and Alzheimer's disease dementia

Cited by 27 publications

References 35 publications

The Experience of Apathy in Dementia: A Qualitative Study

The Experience of Apathy in Dementia: A Qualitative Study

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

Polygenic Risk Score Effectively Predicts Risk of Depression Onset in Alzheimer’s Disease

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