Depression in Patients with Parkinson's Disease: Current Understanding of its Neurobiology and Implications for Treatment.

Depression is one of the most frequent and burdensome non-motor symptoms in Parkinson's disease (PD), across all stages. Even when its severity is mild, PD depression has a great impact on quality of life for these patients and their caregivers. Accordingly, accurate diagnosis, supported by validated scales, identification of risk factors, and recognition of motor and non-motor symptoms comorbid to depression are critical to understanding the neurobiology of depression, which in turn determines the effectiveness of dopaminergic drugs, antidepressants and non-pharmacological interventions. Recent advances using in vivo functional and structural imaging demonstrate that PD depression is underpinned by dysfunction of limbic networks and monoaminergic systems, depending on the stage of PD and its associated symptoms, including apathy, anxiety, rapid eye movement sleep behavior disorder (RBD), cognitive impairment and dementia. In particular, the evolution of serotonergic, noradrenergic, and dopaminergic dysfunction and abnormalities of limbic circuits across time, involving the anterior cingulate and orbitofrontal cortices, amygdala, thalamus and ventral striatum, help to delineate the variable expression of depression in patients with prodromal, early and advanced PD. Evidence is accumulating to support the use of dual serotonin and noradrenaline reuptake inhibitors (desipramine, nortriptyline, venlafaxine) in patients with PD and moderate to severe depression, while selective serotonin reuptake inhibitors, repetitive transcranial magnetic stimulation and cognitive behavioral therapy may also be considered. In all patients, recent findings advocate that optimization of dopamine replacement therapy and evaluation of deep brain stimulation of the subthalamic nucleus to improve motor symptoms represents an important first step, in addition to physical activity. Overall, this review indicates that increasing understanding of neurobiological changes help to implement a roadmap of tailored interventions for patients with PD and depression, depending on the stage and comorbid symptoms underlying PD subtypes and their prognosis.

Neuropsychiatric symptoms and quality of life in Spanish patients with Alzheimer's disease during the COVID-19 lockdown.

BACKGROUND AND PURPOSE: The COVID-19 epidemic is affecting almost all individuals worldwide, and patients with Alzheimer's disease (AD) and amnesic mild cognitive impairment (MCI) are particularly at risk due to their characteristics and age. We analysed the impact of the pandemic on these patients' neuropsychiatric symptoms and their quality of life after 5 weeks of lockdown in Spain. METHODS: A total of 40 patients with a diagnosis of MCI (n = 20) or mild AD (n = 20) from the Cognitive Stimulation Program of the Cognitive Disorders Unit were evaluated. All patients had undergone a previous evaluation during the month before the lockdown, and were re-evaluated after 5 weeks of lockdown. The Neuropsychiatric Inventory (NPI) and EuroQol-5D questionnaire (EQ-5D) were used to assess neuropsychiatric symptoms in patients and the quality of life in patients as well in caregivers. RESULTS: The mean (SD) total baseline NPI score was 33.75 (22.28), compared with 39.05 (27.96) after confinement (P = 0.028). The most frequently affected neuropsychiatric symptoms were apathy [4.15 (3.78) vs. 5.75 (4.02); P = 0.002] and anxiety [3.95 (3.73) vs. 5.30 (4.01); P = 0.006] in patients with MCI, and apathy [2.35 (2.70) vs. 3.75 (3.78); P = 0.036], agitation [0.45 (1.14) vs. 1.50 (2.66); P = 0.029] and aberrant motor behaviour [1.25 (2.86) vs. 2.00 (2.93); P = 0.044] in patients with AD. We did not observe differences in EQ-5D scores during the re-evaluation. The 30% of patients and 40% of caregivers reported a worsening of the patients' health status during confinement. CONCLUSIONS: The results of this study show the worsening of neuropsychiatric symptoms in patients with AD and MCI during 5 weeks of lockdown, with agitation, apathy and aberrant motor activity being the most affected symptoms.