Towards Defining the Neuroanatomical Basis of Late-Onset Psychiatric Symptoms

Abstract

Psychiatric symptoms, including changes in emotional processing, are a common feature of many neurodegenerative disorders, such as Alzheimer's disease, dementia with Lewy Bodies, frontotemporal dementia, and Huntington's disease. However, the neuroanatomical basis of emotional symptoms is not well defined; this stands in contrast to the relatively well-understood neuroanatomical correlates of cognitive and motor symptoms in neurodegenerative disorders. Furthermore, psychiatric diagnostic categories, as defined by the Diagnostic and Statistical Manual of Mental Disorders (DSM) and International Statistical Classification of Diseases and Related Health Problems (ICD), may have limited applicability in patients with late-onset psychiatric symptoms in the context of neurodegenerative disorders. In this clinical review, we suggest that early-onset and late-onset psychiatric symptoms have distinct etiologies, and that late-onset changes in emotional processing are likely underpinned by neurodegenerative disease. Furthermore, we suggest that an improved understanding of the neuroanatomical correlates of emotional changes in neurodegenerative disease may facilitate diagnosis and future treatment development. Finally, we propose a novel clinical approach, in a preliminary attempt to incorporate late-onset emotional symptoms alongside cognitive and motor symptoms into a clinical "algorithm," with a focus on the neuroanatomy implicated when particular combinations of emotional, cognitive, and motor features are present. We anticipate that this clinical approach will assist with the diagnosis of neurodegenerative disorders, and our proposed schema represents a move towards integrating neurologic and psychiatric classification systems.

Keywords: dementia; emotional blunting; neurodegenerative disease; neuropsychiatry.

Figure 1.

Age of onset of primary psychiatric disorders. From Paus et al., 2008.

Figure 2.

Theoretical model of incidence and etiology of psychiatric symptoms by age.

Figure 3.

Neuropathological diagnoses in a large community cohort by cognitive status prior to death. Abbreviations: NCI = No Cognitive Impairment; MCI = Mild Cognitive Impairment; AD = Alzheimer’s disease; V = Vascular; OD = Other Degenerative; 0 = no vascular or neurodegenerative pathology. From Kapasi et al., 2017.

Figure 4.

An additive model of neuropathologies contributing to cognitive impairment. Cognitive status is defined as demented, definitely impaired, or marginal at the last examination prior to death. Lesion indices include AD changes, microvascular ischemic lesions, cortical Lewy bodies, hippocampal sclerosis, and generalized atrophy. From White et al., 2016.

Figure 5.

Flowchart depicting a clinical algorithm to neuroanatomically localize emotional changes observed with neurodegenerative disorders. Neurodegenerative disorders targeting the neuroanatomical regions are listed in italic gray text. Abbreviations: WM = white matter; vmPFC, bvFTD = behavioral variant frontotemporal dementia; svPPA = semantic variant primary progressive aphasia; SD = semantic dementia; AD = Alzheimer’s disease; PD = Parkinson’s disease; DLB = dementia with Lewy Bodies; HD = Huntington’s disease.