Similarities Between Depression and Neurodegenerative Diseases: Pathophysiology, Challenges in Diagnosis and Treatment Options

Abstract

Depressive disorder and neurodegenerative diseases are two different clinical entities. Depression is a common psychiatric disorder in the general population. However, when present concomitantly with neurodegenerative disorders, its diagnosis becomes challenging. In many cases, patients remain undiagnosed and hence, untreated, worsening the prognosis of the neurodegenerative diseases and impairing the quality of life. One of the possible reasons for the difficulties in diagnosis in such cases is that both conditions affect the central nervous system, so there might be an overlap of symptoms leading to a missed diagnosis of depression in a neurodegenerative disease patient and vice versa. Symptoms such as irritability, apathy, and decreased cognition are common to both types of disorders. Some neurodegenerative diseases, especially Alzheimer's disease, can initially present as a depressive prodrome. This may cause a difficulty in differentiating between these two conditions and a diagnosis of either conditions may be missed; hence an opportunity for timely intervention and improved outcomes is missed. An approach towards analyzing and comparing the pathological mechanisms common to both disease types will create a better understanding of depression and neurodegenerative diseases, identify their similarities, and develop improved clinical criteria to help clinicians make a timely diagnosis of these conditions present together. In the present review, various studies related to common pathological links, concomitant diagnosis challenges, and ongoing research about different treatment options are discussed.

Analysis of Factors Associated With Depression in Community-Dwelling Older Adults in Wuhan, China

“…Recurrent major depression was a risk factor for Alzheimer’s disease, also Alzheimer’s disease constituted a risk factor for depression ( Aznar and Knudsen, 2011 ). Reports have revealed that similar changes in the neuroplasticity, morphology, and neurotransmission in the brain seemed to be associated to depression and cognitive dysfunction ( Hussain et al, 2020 ). Alzheimer’s disease intrinsically deteriorates affective regulation, a critical capacity in the resistance to depression in the face of life stresses ( Nash et al, 2007 ).…”

An Evaluation of Right-Sided Symptom Onset as a Predictor of Poor Parkinson’s Disease Prognosis

“…Functional and anatomical differences between the hemispheres have also been demonstrated [ 16 - 17 ]. Many clinical parameters have been evaluated in prognosis studies on patients with PD [ 18 - 20 ]. However, to the best of our knowledge, the impact of the asymmetrical presentation of clinical symptoms on the prognosis of patients with PD has not previously been evaluated, although many researchers believe that motor predominance is essential for a diagnosis of parkinsonism.…”

Insights into the Pathophysiology of Psychiatric Symptoms in Central Nervous System Disorders: Implications for Early and Differential Diagnosis

“…Depressive symptoms are reported in AD prior to mild cognitive impairment (MCI) with a prevalence of about 20% [ 28 , 31 ], as well as in preclinical bvFTD, where a prevalence up to 40% has been described [ 23 , 32 ]. Depression during the preclinical stages of AD and bvFTD can be often associated with other affective symptoms and mood changes [ 15 , 33 ]. Similarly, affective symptoms are already present at the time of diagnosis in PD and HD in a percentage of cases up to 30%, and may precede neurological symptoms of several years [ 5 , 34 , 35 ].…”

“…Noteworthy, depressive and anxiety symptoms are listed among clinical markers of prodromal PD in the most updated diagnostic criteria [ 36 , 37 ]. The lack of an accurate evaluation of psychiatric symptoms, i.e., insufficient attention dedicated to their late-life onset and to a negative personal psychiatric history, often leads to the diagnosis of a primary psychiatric disorder in these subjects [ 15 , 38 ]. As a consequence, inappropriate psychopharmacological treatment is frequently prescribed, further affecting the clinical presentation, and contributing at the same time to the lack of adequate medical care for the underlying neurological condition [ 33 , 39 ].…”

“…In some cases, such symptoms can be reactive to the diagnosis of the CNS disorder itself [ 10 , 11 , 12 ], while in other cases they are reported as possible consequences of pharmacological treatments [ 13 , 14 ]. In addition, the same pathophysiological pathways underlying neurological manifestations can contribute to the development of psychopathological features in CNS disorders, strongly suggesting a neurobiological link between neurological and psychiatric symptoms [ 9 , 15 , 16 ].…”