Late onset depression: dopaminergic deficit and clinical features of prodromal Parkinson’s disease: a cross-sectional study

Abstract

BackgroundLate onset depression (LOD) may precede the diagnosis of Parkinson’s disease (PD) or dementia with Lewy bodies (DLB). We aimed to determine the rate of clinical and imaging features associated with prodromal PD/DLB in patients with LOD.MethodsIn a cross-sectional design, 36 patients with first onset of a depressive disorder (Diagnostic and Statistical Manual of Mental Disorders IV criteria) diagnosed after the age of 55 (LOD group) and 30 healthy controls (HC) underwent a detailed clinical assessment. In addition, 28/36 patients with LOD and 20/30 HC underwent a head MRI and 29/36 and 25/30, respectively, had dopamine transporter imaging by 123I-ioflupane single-photon emission computed tomography (SPECT) imaging. Image analysis of both scans was performed by a rater blind to the participant group. Results of clinical assessments and imaging results were compared between the two groups.ResultsPatients with LOD (n=36) had significantly worse scores than HC (n=30) on the PD screening questionnaire (mean (SD) 1.8 (1.9) vs 0.8 (1.2); p=0.01), Movement Disorder Society Unified Parkinson’s Disease Rating Scale total (mean (SD) 19.2 (12.7) vs 6.1 (5.7); p<0.001), REM-sleep behaviour disorder screening questionnaire (mean (SD) 4.3 (3.2) vs 2.1 (2.1); p=0.001), Lille Apathy Rating Scale (mean (SD) −23.3 (9.6) vs −27.0 (4.7); p=0.04) and the Scales for Outcomes in PD-Autonomic (mean (SD) 14.9 (8.7) vs 7.7 (4.9); p<0.001). Twenty-four per cent of patients with LOD versus 4% HC had an abnormal 123I-ioflupane SPECT scan (p=0.04).ConclusionsLOD is associated with increased rates of motor and non-motor features of PD/DLB and of abnormal 123I-ioflupane SPECTs. These results suggest that patients with LOD should be considered at increased risk of PD/DLB.

Locus Coeruleus Malfunction Is Linked to Psychopathology in Prodromal Dementia With Lewy Bodies

“…The assessment of DLB's typical core features can be confounded by psychiatric symptoms, thereby hindering a bradykinesia assessment or neuropsychological testing. Recent evidence suggests that the frequent detection of nigrostriatal deficit via 123I-FP-CIT SPECT as an indicative biomarker for DLB in patients presenting late-onset depression (Kazmi et al, 2020) might support the hypothesis that DLB begins as a lateonset psychiatric disorder. Diverse studies provided evidence that psychiatric symptoms such as acoustic hallucinations, delusions, and depressive symptoms at disease onset are much more often present in DLB than in AD patients in clinically diagnosed DLB and autopsy-confirmed DLB patients (Ballard et al, 1999).…”

“…We know that mainly dopaminergic neuronal loss in the ventral tegmental area (VTA), but not LC is diagnosed in patients presenting symptoms of late-onset depression, and in post-mortem evidence of Lewy bodies (Wilson et al, 2013). These findings were recently corroborated by the fact that 24% of patients suffering from late-onset depression exhibited a nigrostriatal dopaminergic deficit in 123I-Ioflupane SPECT (Kazmi et al, 2020). However, the VTA is not the only source of dopamine, as it can also be released from LC terminals in the hippocampus (Kempadoo et al, 2016) and prefrontal cortex (Devoto et al, 2020) indicating that a neuronal LC loss could entail impaired dopamine release as a possible consequence.…”

Older adults respond better to psychological therapy than working-age adults: evidence from a large sample of mental health service attendees.

“…A quarter of older adults (over 65s) have a common mental disorder (CMD) such as depression or an anxiety disorder ( Evans and Mottram, 2000 ; Gowling et al., 2016 ). CMDs in older adults are associated with negative outcomes including increased risk of cognitive impairment and dementia ( Byers and Yaffe, 2011 ; Kazmi et al., 2021 ) and earlier mortality ( Saz and Dewey, 2001 ). Psychological therapies such as cognitive behaviour therapy (CBT) are proven to be effective ( NICE, 2011 ), there is a patient preference for psychological therapies over antidepressant medications ( Cuijpers et al., 2020 ; McHugh et al., 2013 ), and there are fewer adverse side-effects ( Carvalho et al., 2016 ).…”

Assessing Nigrostriatal Dopaminergic Pathways via 123I-FP-CIT SPECT in Dementia With Lewy Bodies in a Psychiatric Patient Cohort

“…However, most patients diagnosed with a neurodegenerative or major psychiatric disorder exhibited similar psychotic symptoms ( Schutte et al, 2020 ) indicating the need for a biological marker such as 123I-FP-CIT SPECT to better differentiate these disorders, as they share similarities in their phenotypical appearance. The late-onset of a major psychiatric disorder such as late-onset depression might imply a neurodegenerative etiology potentially detectable via 123I-FP-CIT SPECT, such as Parkinson’s disease or DLB ( Kazmi et al, 2021 ) especially when other neuroimaging findings are unremarkable. Our results reveal that in DLB patients suffering from psychiatric symptoms, 123I-FP-CIT SPECT plays a key role in diagnosing probable DLB.…”