Apathy as a feature of prodromal Alzheimer's disease: an FDG‐PET ADNI study

Delrieu, Julien; Desmidt, Thomas; Camus, Vincent; Sourdet, Sandrine; Boutoleau‐Bretonnière, Claire; Mullin, Emmanuel; Vellas, Bruno; Payoux, Pierre; Lebouvier, Thibaud; Initiative, Alzheimer’s Disease Neuroimaging

doi:10.1002/gps.4161

Cited by 53 publications

(44 citation statements)

References 56 publications

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“…[59] Numerous studies have identified apathy as an early and common behavioral symptom in MCI and AD dementia linked to clinical progression[59, 60] and, recently, to posterior cingulate cortex hypometabolism in amnestic MCI. [61] Our current findings suggest that apathy and anhehonia may also signal early neurodegeneration and, thereby, increased vulnerability to clinical decline, in CN elderly. Apathy-andedonia factor scores in our sample were also significantly associated with high amyloid burden in unadjusted bivariate analyses, implicating AD pathophysiology, and in line with evidence of an association of greater apathy with high amyloid at the stage of MCI.…”

Section: Discussionmentioning

confidence: 75%

Depressive Symptoms and Biomarkers of Alzheimer’s Disease in Cognitively Normal Older Adults

Donovan

Hsu

Dagley

et al. 2015

JAD

104

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Even low levels of depressive symptoms are associated with an increased risk of cognitive decline in older adults without overt cognitive impairment (CN). Our objective was to examine whether very low, “subthreshold symptoms of depression” (SSD) are associated with Alzheimer’s disease (AD) biomarkers of neurodegeneration in CN adults and whether these associations are specific to particular depressive symptoms. We analyzed data from 248 community-dwelling CN older adults, including measurements of cortical amyloid burden, neurodegeneration markers of hippocampal volume (HV) and cerebral 18F-fluorodeoxyglucose (FDG) metabolism in a composite of AD-related regions and the 30-item Geriatric Depression Scale (GDS). Participants with GDS>10 were excluded. General linear regression models evaluated the cross-sectional relations of GDS to HV or FDG in separate backward elimination models. Predictors included GDS total score, age, sex, premorbid intelligence, a binary amyloid variable and its interaction with GDS. Principal component analyses of GDS item scores revealed three factors (the Dysphoria, Apathy-Anhedonia and Anxiety-Concentration Factors). In secondary analyses, GDS total score was replaced with the three factor scores in repeated models. Higher GDS score (p=0.03) was significantly associated with lower HV and was marginally related (p=0.06) to FDG hypometabolism. In secondary models, higher Dysphoria (p=0.02) and Apathy-Anhedonia (p=0.05) were related to lower HV while higher Apathy-Anhedonia (p=0.003) was the sole factor related to FDG hypometabolism. Amyloid was not a significant predictor in any model. In conclusion, very low-level dysphoria, apathy and anhedonia may point to neurodegeneration in AD-related regions but this association appears to be independent of amyloid burden.

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Section: Discussionmentioning

confidence: 75%

Depressive Symptoms and Biomarkers of Alzheimer’s Disease in Cognitively Normal Older Adults

Donovan

Hsu

Dagley

et al. 2015

JAD

104

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“…Similarly apathy is associated with decreased perfusion in ACC (Benoit et al, 2004; Lanctôt et al, 2007; Robert et al, 2006), decreased ACC white matter integrity by DTI (Hahn et al, 2013; Kim et al, 2011; Ota et al, 2012) and increased amyloid burden in right ACC (Mori et al, 2014). Apathy is also associated with decreased PCC metabolism (Delrieu et al, 2015). There are also links between apathy and volume loss and/or cortical thinning in frontal cortex (Apostolova et al, 2007; Bruen et al, 2008; Stanton et al, 2013; Tunnard et al, 2011), though there is no strict concordance on the specific regions of frontal cortex which include medial, lateral, and orbital regions.…”

Section: Resultsmentioning

confidence: 99%

Neuropsychiatric symptoms in Alzheimer's disease: What might be associated brain circuits?

Rosenberg

Nowrangi

Lyketsos

2015

Molecular Aspects of Medicine

259

178

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Neuropsychiatric symptoms (NPS) are very common in Alzheimer’s disease (AD), particularly agitation, apathy, depression, and delusions. Brain networks or circuits underlying these symptoms are just starting to be understood, and there is a growing imaging and neurochemical evidence base for understanding potential mechanisms for NPS. We offer a synthetic review of the recent literature and offer hypotheses for potential networks/circuits underlying these NPS, particularly agitation, apathy, and delusions. Agitation in AD appears to be associated with deficits in structure and function of frontal cortex, anterior cingulate cortex, posterior cingulate cortex, amygdala, and hippocampus, and may be associated with mechanisms underlying misinterpretation of threats and affective regulation. Apathy in AD is associated with frontal cortex, anterior cingulate cortex, posterior cingulate cortex, as well as orbitofrontal cortex, and inferior temporal cortex, and may be associated with mechanisms underlying avoidance behaviors.

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“…Many data established a possible link between apathy and AD with a decreased reliability of ACC network, mainly due to an increased generalized amyloid depositions (Canevelli et al, 2013), a volume loss in ACC (Apostolova et al, 2007; Bruen et al, 2008; Marshall et al, 2013; Stanton et al, 2013), a decreased perfusion in ACC (Benoit et al, 2004; Lanctôt et al, 2007; Tunnard et al, 2011), a decreased ACC white matter related integrity (Robert et al, 2006; Kim et al, 2011; Hahn et al, 2013), and increased amyloid burden in right ACC (Ota et al, 2012; Mori et al, 2014). Apathy is also associated with decreased posterior cingulate (PCC metabolism; Migneco et al, 2001), with a reduced insular volume (Moon et al, 2014a; Delrieu et al, 2015), and with decreased inferior temporal cortical (ITC) thickness (Moon et al, 2014b; Guercio et al, 2015), with cortical shrinkage of the frontal cortex (Apostolova et al, 2007; Bruen et al, 2008; Marshall et al, 2013; Stanton et al, 2013), with greater amyloid burden in bilateral frontal cortex (Ota et al, 2012), reduced orbitofrontal metabolism on the left (Donovan et al, 2014) or right (Benoit et al, 2004), and reduced connectivity in left-sided functional connectivity, with thalamus and parietal cortex, and amygdala (Holthoff et al, 2005; Kang et al, 2012; Ota et al, 2012; Baggio et al, 2015). Galantamine, as a cholinesterase inhibitor has been linked to a slower decrease of the putamen metabolism (Zhao et al, 2014), based on FDG-PET study (Zhao et al, 2014).…”

Section: What Do We Know About Apathy From Clinical Practice?mentioning

confidence: 99%

“…Data are not univocal (Donovan et al, 2014; Delrieu et al, 2015). One fMRI study found alterations in functional limbic-hypothalamic networks in relation to apathy (Tatemichi et al, 1992; Starkstein et al, 1997; Balthazar et al, 2014).…”

Section: What Do We Know About Apathy From Clinical Practice?mentioning

confidence: 99%

Neural Correlates for Apathy: Frontal-Prefrontal and Parietal Cortical- Subcortical Circuits

Moretti

Signori

2016

Front. Aging Neurosci.

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Apathy is an uncertain nosographical entity, which includes reduced motivation, abulia, decreased empathy, and lack of emotional involvement; it is an important and heavy-burden clinical condition which strongly impacts in everyday life events, affects the common daily living abilities, reduced the inner goal directed behavior, and gives the heaviest burden on caregivers. Is a quite common comorbidity of many neurological disease, However, there is no definite consensus on the role of apathy in clinical practice, no definite data on anatomical circuits involved in its development, and no definite instrument to detect it at bedside. As a general observation, the occurrence of apathy is connected to damage of prefrontal cortex (PFC) and basal ganglia; “emotional affective” apathy may be related to the orbitomedial PFC and ventral striatum; “cognitive apathy” may be associated with dysfunction of lateral PFC and dorsal caudate nuclei; deficit of “autoactivation” may be due to bilateral lesions of the internal portion of globus pallidus, bilateral paramedian thalamic lesions, or the dorsomedial portion of PFC. On the other hand, apathy severity has been connected to neurofibrillary tangles density in the anterior cingulate gyrus and to gray matter atrophy in the anterior cingulate (ACC) and in the left medial frontal cortex, confirmed by functional imaging studies. These neural networks are linked to projects, judjing and planning, execution and selection common actions, and through the basolateral amygdala and nucleus accumbens projects to the frontostriatal and to the dorsolateral prefrontal cortex. Therefore, an alteration of these circuitry caused a lack of insight, a reduction of decision-making strategies, and a reduced speedness in action decision, major responsible for apathy. Emergent role concerns also the parietal cortex, with its direct action motivation control. We will discuss the importance of these circuits in different pathologies, degenerative or vascular, acute or chronic.

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Apathy as a feature of prodromal Alzheimer's disease: an FDG‐PET ADNI study

Abstract: The presence of apathy in MCI patients is associated with AD-specific pattern of brain metabolic defect. These results could suggest that apathy belongs to the spectrum of prodromal AD symptoms.

Cited by 53 publications

References 56 publications

Depressive Symptoms and Biomarkers of Alzheimer’s Disease in Cognitively Normal Older Adults

Depressive Symptoms and Biomarkers of Alzheimer’s Disease in Cognitively Normal Older Adults

Neuropsychiatric symptoms in Alzheimer's disease: What might be associated brain circuits?

Neural Correlates for Apathy: Frontal-Prefrontal and Parietal Cortical- Subcortical Circuits

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