Neurodegeneration, β‐amyloid and mood disorders: state of the art and future perspectives

Piccinni, Armando; Origlia, Nicola; Veltri, Antonello; Vizzaccaro, Chiara; Marazziti, Donatella; Vanelli, Federica; Moroni, Ilenia; Domenici, Luciano; Dell’Osso, Liliana

doi:10.1002/gps.3879

Cited by 14 publications

(10 citation statements)

References 189 publications

(221 reference statements)

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“…The authors suggested that depression could reflect a prodromal stage of dementia. In this scenario, a significant reduction of β-amyloid peptide and a high Aβ40/Aβ42 ratio in depressed patients have been reported and these findings increase the risk for dementia 22 . However, this result remains to be clarified since another group that aimed to analyze the impact of depression on incident dementia developed a population-based prospective study of a large cohort of the elderly and the authors found no clear association between both conditions 23 .…”

Section: Discussionmentioning

confidence: 92%

Cortical correlates of affective syndrome in dementia due to Alzheimer’s disease

Hayata

Bergo

Rezende

et al. 2015

Arq. Neuro-Psiquiatr.

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Neuropsychiatric syndromes (NPS) in dementia due to Alzheimer' s disease (AD) have received growing attention across clinical centers and research settings in the last few decades. The high prevalence of NPS and their increasing severity in AD patients aggravate the disease' s course and cause distress for caregivers. These symptoms, once considered secondary behavior due to cognitive and functional impairment in dementia, have shown patterns of temporal course, which do not necessarily follow the linear decline of cognitive impairment.Several NPS seem to be more prevalent and clinically prominent in distinct stages of the disease. Depression is the most common syndrome in mild-to-moderate AD, while delusions, hallucinations, and aggression seem to be more common as the disease progresses, whereas apathy remains across all stages of AD, worsening as the global deterioration aggravates. However, these manifestations, also detected in mild cognitive impairment (MCI), increase the risk of dementia and may occur in prodromal AD.Moreover, aberrant vocalizations commonly emerge when patients are in advanced stages of dementia. Despite the fact that NPS and cognitive alterations may considerably overlap, these findings suggest distinct etiologies for both conditions. Furthermore, over the course of the disease, the prevalence of NPS reaches 50-90% of patients with dementia AbstrACtNeuropsychiatric symptoms in Alzheimer's disease (AD) are prevalent, however their relationship with patterns of cortical atrophy is not fully known. Objectives: To compare cortical atrophy's patterns between AD patients and healthy controls; to verify correlations between neuropsychiatric syndromes and cortical atrophy. Method: 33 AD patients were examined by Neuropsychiatric Inventory (NPI). Patients and 29 controls underwent a 3T MRI scanning. We considered four NPI syndromes: affective, apathy, hyperactivity and psychosis. Correlations between structural imaging and neuropsychiatric scores were performed by Freesurfer. Results were significant with a p-value < 0.05, corrected for multiple comparisons. Results: Patients exhibited atrophy in entorhinal cortices, left inferior and middle temporal gyri, and precuneus bilaterally. There was correlation between affective syndrome and cortical thickness in right frontal structures, insula and temporal pole. Conclusion: Cortical thickness measures revealed atrophy in mild AD. Depression and anxiety symptoms were associated with atrophy of right frontal, temporal and insular cortices.Keywords: depression, anxiety, MRI, neurodegenerative disease, neuropsychiatry. resumo Os sintomas neuropsiquiátricos na doença de Alzheimer (DA) são prevalentes, porém suas relações com padrões de atrofia cortical não são totalmente compreendidas. Objetivos: Comparar padrões de atrofia cortical entre DA e controles; verificar se há correlações entre sintomas neuropsiquiátricos e atrofia cortical. Método: 33 pacientes com DA foram examinados pelo Inventário Neuropsiquiátrico. Os pacientes e 29 controles foram submeti...

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Section: Discussionmentioning

confidence: 92%

Cortical correlates of affective syndrome in dementia due to Alzheimer’s disease

Hayata

Bergo

Rezende

et al. 2015

Arq. Neuro-Psiquiatr.

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“…Moreover, the serotoninergic system is altered in AD (Trillo et al, 2013 ; Ramirez et al, 2014 ; Verdurand and Zimmer, 2017 ), and amyloid deposition in the brain impairs the serotoninergic activity in animal models (Colaianna et al, 2010 ; Ledo et al, 2013 ). Aβ peptides display neurotoxic activity (Piccinni et al, 2013 ), and they could also alter the brain inflammatory response, which in turn modifies the expression of indoleamine2,3-dioxygenase and impairs serotoninergic transmission (Ledo et al, 2013 ; Mahgoub and Alexopoulos, 2016 ). Hence, in early stage AD, suicidal behavior could be related to alterations of serotoninergic transmission (Madsen et al, 2011 ), which have been linked to impulsive and aggressive behavior (Lai et al, 2003 ; Vermeiren et al, 2014 ).…”

Section: Resultsmentioning

confidence: 99%

A Complex Relationship Between Suicide, Dementia, and Amyloid: A Narrative Review

et al. 2018

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Background: Suicide rates are high among older adults and many conditions have been related to suicide in this population: chronic illnesses, physical disabilities, cancer, social isolation, mental disorders and neurocognitive disorders.Objectives: Among neurocognitive disorders, analysis of the relationships between dementia and suicidal behaviors led to conflicting results and some questions are still without answer. Particularly, it is not known whether (i) Alzheimer's disease (AD) increases the risk of suicidal ideation and suicide attempts (SA) or the frequency of death by suicide; (ii) the presence of suicidal ideation or SA in people older than 65 years of age is an early dementia sign; and (iii) amyloid load in frontal areas facilitates SA by modifying the decision-making pathway.Methods: Therefore, in this narrative review, we searched the PubMed database using the medical subject heading (MeSH) terms (“Suicide” AND “Depression”) OR (“Amyloid” OR “Dementia”) to identify recent (from 2000 to 2017) original studies on the links between suicidal behavior, dementia and brain amyloid load. We also explored the clinical and pathophysiological role of depression in these relationships.Results and Discussion: The findings from these studies suggest that late stage dementia could protect against suicidal ideation and SA. Conversely, the risk of complete suicide is increased during the early phase of cognitive decline.Conclusions: Serious cognitive impairment and decline of executive functions could protect against negative thoughts related to cognitive disability awareness and against suicide planning.Several factors, including brain amyloid load, could be involved in the increased suicide rate early after the diagnosis of dementia.

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“…In depression, the serum A␤ 40/42 ratio (a peripheral marker of brain AD pathology) is elevated in depressed compared with non-depressed individuals consistently across studies, even in participants aged below 40 years [177]. Studies using cerebrospinal fluid markers of A␤ 42 , arguably a more reliable measure of AD pathology, yield mixed results, showing lower, equal or greater levels in depressed versus non-depressed individuals [177].…”

Section: Annex 1: Ad Pathologymentioning

confidence: 99%

Cognitive Debt and Alzheimer's Disease

Marchant

Howard

2015

JAD

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We propose the concept of Cognitive Debt to characterize thoughts and behaviors that increase vulnerability to symptomatic Alzheimer's disease (AD). Evidence indicates that depression, anxiety, sleep disorder, neuroticism, life stress, and post-traumatic stress disorder increase risk for AD, and we suggest they do so by increasing Cognitive Debt. Repetitive negative thinking (RNT), a behaviorally measurable process common to these factors, may drive Cognitive Debt acquisition. RNT transcends disorder-specific definition, encompasses rumination and worry, and is defined by perseverative, negative thought tendencies. Evidence of dysregulated stress responses supports the concept of Cognitive Debt, of RNT as its causal mechanism, and of an interaction with the APOE-ε4 genotype to increase vulnerability to clinical AD, independent from traditional AD pathology. Defining a more specific behavioral profile of risk would enable interventions to be targeted earlier and more precisely at individuals most vulnerable to developing AD. Additionally, modulating RNT could potentially reduce risk of clinical AD. Interventions to reduce RNT are discussed, as are suggestions for future research. For these reasons we submit that the Cognitive Debt model may aid understanding of the psychological mechanisms that potentially increase predisposition to AD.

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Neurodegeneration, β‐amyloid and mood disorders: state of the art and future perspectives

Abstract: Given the intriguing association between change in plasma level of Aβ, depression and cognitive impairment, future work should focus on the relationship between Aβ peripheral level(s), biomarkers of neurodegeneration and development of dementia in patients affected by mood disorders.

Cited by 14 publications

References 189 publications

Cortical correlates of affective syndrome in dementia due to Alzheimer’s disease

Cortical correlates of affective syndrome in dementia due to Alzheimer’s disease

A Complex Relationship Between Suicide, Dementia, and Amyloid: A Narrative Review

Cognitive Debt and Alzheimer's Disease

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