Are Apathy and Depression Independently Associated with Longitudinal Trajectories of Cortical Atrophy in Mild Cognitive Impairment?

Abstract

Objective We sought to examine whether depression and apathy are independently associated with longitudinal trajectories of cortical atrophy in entorhinal cortex compared to frontal subregions previously implicated in late-life mood disturbance. Design Data from 334 participants classified as having Mild Cognitive Impairment (MCI) in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) were analyzed using multilevel models for change adjusted for age, global cognitive status, and total intracranial volume at enrollment. Setting Participants in ADNI were recruited from over 50 clinical research sites in the United States and Canada. Measurements Depression and apathy were identified by informants with the Neuropsychiatric Inventory Questionnaire. Serial MRI was carried out on 1.5T scanners according to standardized ADNI-1 protocol on an average of 5 occasions over an average of 2.5 years. Regional cortical thickness values were derived from longitudinal data processing in Freesurfer version 4.4. Results Depression was associated with reduced cortical thickness in the entorhinal cortex at baseline and accelerated atrophy in anterior cingulate cortex. Similarly-sized relationships between depression and orbitofrontal cortex and between apathy and anterior cingulate cortex were not significant. Conclusions In MCI, depression signs are a better marker of longitudinal cortical atrophy than apathy. Results are consistent with hypotheses that depression is an early sign of a more aggressive neurodegenerative process or that depression lowers brain reserve capacity, allowing for more rapid progression of AD neuropathology.

Chronic Depressive Symptomatology in Mild Cognitive Impairment Is Associated with Frontal Atrophy Rate which Hastens Conversion to Alzheimer Dementia

“…It has been suggested that changes in the serotonergic system driven by neurodegeneration in adjacent cholinergic system may induce depression and accelerate cognitive impairment (32). Thus, our findings could also be explained by a progression of the underlying MCI neurodegenerative pathology, as previously suggested (16, 17). We cannot exclude, however, yet another explanation, namely that chrDS in MCI may represent an atypical neurodegenerative pattern with additional frontal and ACC atrophy, a line of thought supported by studies of atypical AD (33).…”

“…In a study of depressive symptoms assessed at baseline in relation to longitudinal brain changes in MCI, depressive symptoms were associated with accelerated cortical atrophy in ACC (16). A more recent study in MCI found that chronic, but not baseline depressive symptoms were associated with bilateral frontoparietotemporal white matter (WM) atrophy and consequently with an increased risk to develop AD (17).…”

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

“…Mendez et al, for example, verified a correlation between anxiety and dysthymia with hypoperfusion of the right temporal lobe 13 . Other studies have also examined the correlation between depression and a reduction in cortical thickness on the entorhinal cortex and the anterior cingulated cortex 14 . Because of these findings, it is possible to note the relevance of correlations between affective syndrome and the frontal and temporal lobes.…”

Apathy in Parkinson's disease: clinical features, neural substrates, diagnosis, and treatment

“…7,55 Both dopaminergic denervation and cholinergic abnormalities aff ect the lateral and medial regions of the prefrontal cortex in Parkinson's disease. Degeneration of mesencephalic dopaminergic neurons at Braak stage III of the disease leads to dopamine depletion in the mesocortical and mesolimbic systems, 56 and the spread of synucleinopathy to subcortical and cortical dopamine projection areas further impairs their functionality during Braak stages IV and V. 57,58 Delineation of the diff erent components that can lead to apathy is crucial to the planning of therapeutic strategies.…”