The Neuropsychiatric Inventory: Development & Applications

Key Messages

• The Neuropsychiatric Inventory (NPI) is a reliable tool developed to capture a large scope of neuropsychiatric symptoms.
• NPI’s utility and applicability is global and show significant impact in clinical trials.
• The NPI has traversed clinical symptomatology and neurobiological data to provide key insights into the pathophysiology of neurodegenerative disorders.

Background

• The Neuropsychiatric Inventory (NPI) has been utilized to assess neuropsychiatric symptoms that occur in patients with Alzheimer disease (AD) and other neurodegenerative disorders (NDD).
  • NPI has been instrumental in clinical research that required neuropsychiatric data collection.
  • NPI has been translated into more than 40 languages, which facilitated its use in global clinical trials and international research efforts.
  • Correlation of NPI scores to brain imaging and cerebrospinal fluid (CSF) helps elucidate underlying neurophysiology of NDD associated neuropsychiatric syndrome (NPS).

 Purpose & Methodology

• The article reviews the history of NPI development and expansion, the application of each NPI version, and clinical applications of research findings based on the NPI.

Results

• Development of the NPI
  • NPI was built to capture a wider range of behaviors that existing instruments did not, such as apathy and disinhibition.
  • The development of NPI also considered NPS symptoms distinct from a primary psychiatric diagnosis such as schizophrenia or major depression and was intended to assess behavioral changes that accompany NDD disease progression.
  • Convergent validity of NPI was ensured using available instruments, such as the Cohen-Mansfield Agitation Inventory (CMAI).
• Versions of the NPI
  • The expansion of the NPI reflects the various clinical settings and care providers involved for most appropriate measurements.
    • The most widely used 12-item NPI version integrated measurement of caregiver distress that influences the characterization of patient behavior.
    • NPI-Nursing Home (NPI-NH) version allows NPI utilization in residential facilities and inpatient settings with nonfamily professional caregiver reports.
    • NPI-Clinician (NPI-C) version is more comprehensive and allows an expert (clinician) perspective of the patient’s behavioral frequency and severity.
  • Translations and International Applications of the NPI
    • Translations of the NPI are available in over 40 languages and are reliable to assess behavioral disturbances across global populations. However, heterogeneity across global regions have been observed and requires further research.
  • Characterizing Behavioral Changes in NDDs with the NPI
    • NPI can capture distinct behavioral profiles across NDDs and provide insight into the underlying neuropathophysiology.
      • AD patients present behavioral changes that correlate with disease course and include NPI measured psychosis, mood, apathy, and agitation.
      • Behavioral profiles in Frontotemporal Dementia (FTD) using NPI include greater elation, apathy, disinhibition, and lower psychosis levels compared to AD profiles.
      • NPI has been utilized for quantitation of complex and specific composition of symptoms associated with dementia with Lewy bodies (DLB).
      • NPI profiles of patients with dementia associated with Parkinson disease (PD) show globally abnormal behavior characteristics compared to PD patients with stable cognition.
      • NPI utilization to assess NPS in wide-ranging neurological disorders show a high prevalence of apathy across many types of NDD.
    • The NPI and the Neurobiology of Behavior
      • NPI data has revealed informative connections between behavior and correlative brain physiology
        • Agitation profiles have been linked to frontal lobe hypometabolism confirmed by fluorodeoxyglucose positron emission tomography (FDG-PET).
        • Occipital lobe and orbitofrontal dysfunctions are associated with NPI determined hallucinations and disinhibition, respectively.
        • Disinhibition has been further linked to the frontal polar and inferior orbital frontal cortex in AD patients.
      • NPI in Clinical Trials
        • NPI has been useful in trials of cognitive-enhancing drugs and to provide safety measures in studies of disease-modifying agents.
        • NPI has played key roles in trials to determine baseline severity for a trial population, primary, and secondary outcome measures.
      • Caregiver Burden, Cost of Care, and Other Research Areas Informed by the NPI
        • Small differences in NPI scores may reflect significant costs to care due to outcomes in patient institutionalization.
      • Challenges with Use of the NPI
        • NPI’s wide scope of NPS characterization is less appropriate for domain-specific studies of psychotropic agents.
        • Behavior assessments on sexual demeanor and impulse control cannot be addressed using NPI.

Conclusions

• The development and evolvement of the NPI strived to meet the dynamic clinical needs of the patient population, caregiver, and care providers.
• The NPI reliably provides behavioral disturbances across world regions and shows common effects for patients suffering from NDD and associated caregiver burden.
• Studies with NPI have effectively linked behavioral changes to neuroanatomical function.

Clinical Implications

• The complex behavioral characteristics captured by NPI may facilitate differential diagnosis of NDD with overlapping symptoms.
• Associated neurophysiological insights provided by NPI can help determine resource needs of patients and their caregivers.
• Use of NPI in clinical trials have contributed to the development of key therapies for patients suffering from NDD.