Understanding neuropsychiatric symptoms in Alzheimer’s disease: challenges and advances in diagnosis and treatment

Abstract

Neuropsychiatric symptoms (NPS) in Alzheimer’s disease (AD) affect up to 97% of AD patients, with an estimated 80% of current AD patients experiencing these symptoms. Common AD-associated NPS include depression, anxiety, agitation, aggression, and apathy. The severity of NPS in AD is typically linked to the disease’s progression and the extent of cognitive decline. Additionally, these symptoms are responsible for a significant increase in morbidity, mortality, caregiver burden, earlier nursing home placement, and greater healthcare expenditure. Despite their high prevalence and significant impact, there is a notable lack of clinical research on NPS in AD. In this article, we explore and analyze the prevalence, symptom manifestations, challenges in diagnosis, and treatment options of NPS associated with AD. Our literature review reveals that distinguishing and accurately diagnosing the NPS associated with AD remains a challenging task in clinical settings. It is often difficult to discern whether NPS are secondary to pathophysiological changes from AD or are comorbid psychiatric conditions. Furthermore, the availability of effective pharmaceutical interventions, as well as non-pharmacotherapies for NPS in AD, remains limited. By highlighting the advance and challenges in diagnosis and treatment of AD-associated NPS, we aspire to offer new insights into the complexity of identifying and treating these symptoms within the context of AD, and contribute to a deeper understanding of the multifaceted nature of NPS in AD.

Exploring the Genetic Landscape of Mild Behavioral Impairment as an Early Marker of Cognitive Decline: An Updated Review Focusing on Alzheimer’s Disease

“…Neuropsychiatric symptoms (NPSs), including depression, anxiety, apathy, agitation, irritability, disinhibition, hallucinations, and delusions, are very common manifestations of AD dementia, since up to 97% of AD patients display at least one NPS during the course of the disease [ 5 ]. NPSs have been related to increased mortality, worse quality of life, functional disability, increased caregiver burden and overall healthcare costs as well as a higher likelihood of placement in nursing homes [ 5 ]. The relationship between NPSs and cognitive decline is not linear, implying that at least partially diverse pathogenic mechanisms might underlie the cognitive and neuropsychiatric axis of neurodegenerative diseases [ 6 ].…”

“…Although NPSs have become more common as the disease progresses, they may occur at prodromal and preclinical stages, even before the manifestation of cognitive impairment [ 5 , 7 ]. NPSs, including depression and anxiety, might also be the presenting symptoms of AD [ 5 , 6 ].…”

“…Although NPSs have become more common as the disease progresses, they may occur at prodromal and preclinical stages, even before the manifestation of cognitive impairment [ 5 , 7 ]. NPSs, including depression and anxiety, might also be the presenting symptoms of AD [ 5 , 6 ]. While the clinical profile of NPSs in manifested AD is well characterized, our understanding of NPSs at the preclinical and prodromal stages of AD at a clinical and neurobiological level has been insufficient.…”

Transcranial magneto-acoustic stimulation improves spatial memory and modulates hippocampal neural oscillations in a mouse model of Alzheimer's disease

“…The deposition of amyloid beta and the formation of neurofibrillary tangles are the pathological processes associated with AD (Yokoyama et al, 2022 ). These pathological features have the potential to disrupt synaptic and neuronal activity, causing network abnormalities in various brain regions (Casula et al, 2022 ; Luo et al, 2023 ; Pless et al, 2023 ). In the brains of AD patients, various neurophysiological features have been detected, including hyperexcitability in the precuneus cortex (Casula et al, 2023 ) and impairment of cerebellar-cortical plasticity mechanisms (Di Lorenzo et al, 2020 ).…”

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“…Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that represents the most common cause of dementia in the elderly [ 1 ]. Typical clinical manifestations include declarative memory deterioration, temporal and spatial disorientation, language difficulties, judgment problems, and other cognitive impairments [ 2 ]. The key pathological feature of AD is the accumulation of beta-amyloid (Aβ) plaques and neurofibrillary tangles [ 3 ].…”