• Select the area you would like to search.
  • ACTIVE INVESTIGATIONS Search for current projects using the investigator's name, institution, or keywords.
  • EXPERTS KNOWLEDGE BASE Enter keywords to search a list of questions and answers received and processed by the ADNI team.
  • ADNI PDFS Search any ADNI publication pdf by author, keyword, or PMID. Use an asterisk only to view all pdfs.
Principal Investigator  
Principal Investigator's Name: Haroon Burhanullah
Institution: Johns Hopkins University
Department: Geriatric Neuropsychiatry
Proposed Analysis: ADNI PROPOSAL: Neuropsychiatric symptoms (NPS) are common in pre- clinical Alzheimer’s disease (AD) (Ref) and mild cognitive impairment. NPS are common in MCI and are associated with poorer cognitive and psychosocial function within MCI cohorts and confer a greater risk for conversion to dementia in comparison with MCI patients without NPS. There has been considerable progress in identifying early cognitive and biomarker predictors of Alzheimer’s disease incidence, with increasing evidence that Neuropsychiatric symptoms may indicators of pre-clinical Alzheimer’s disease. Mild Behavioral Impairment (MBI) is a construct that describes the emergence at ≥ 50 years of age of sustained and impactful neuropsychiatric symptoms. MBI describes NPS of any severity, which are not captured by traditional psychiatric nosology, persist for at least 6 months, and occur in advance of or in concert with Mild Cognitive Impairment (MCI). MBI concept is operationalizing the idea that neuropsychiatric symptoms may help identify persons with preclinical or prodromal dementia. We will be collaborating with the premier investigator of the MBI concept, Zahinoor Ismail at University of Calgary, who has developed an algorithm for mapping scores from the Neuropsychiatric Inventory (NPI) onto the 5 domains of the MBI. In this way, NPI data can be used to approximate the definition of MBI. Ismail and colleagues developed a transformational algorithm that maps NPI items onto MBI domains. The conversion was explained in a paper (Sheikh et. al 2017). NPS was assessed using the informant-rated Neuropsychiatric Inventory Questionnaire (NPI-Q) completed by a family member or close informant. The NPI-Q assesses the presence and severity of ten NPS (delusions, hallucinations, agitation/aggression, dysphoria/depression, anxiety,irritability, disinhibition, euphoria, apathy, aberrant motor behavior) and two neurovegetative domains (sleep and night-time behavior change, and appetite/eating change). MBI was assessed in accordance with the ISTAART-AA research diagnostic criteria (Ismail et al.,2016). Ten NPS domains from the NPI-Q were used to operationalize the five ISTAART-AA MBI domains of decreased motivation (NPI-Q apathy/indifference); emotional/ affective dysregulation (NPI-Q depression/dysphoria, anxiety, elation/euphoria); impulse dyscontrol (NPI-Q agitation/aggression, irritability liability, aberrant motor behavior); social inappropriateness (NPI-Q disinhibition); and abnormal perception or through content (NPI-Q delusions, hallucinations). Presence of at least one behavior comprising a specific domain meant the domain criteria was met. The neurovegetative domains of sleep and appetite changes, as described in the NPI-Q, are not reflected in the ISTAART-AA MBI criteria. MBI was stated to be present if at least one of the five domains were present. Since MBI requires 6 month of NPS symptoms and NPI has 1 month reference range, they have included only those with NPI at 2 successive time points 6 months apart. It results in smaller n, but a larger and more specific signal. Data analysis plan: 1.As a first step, we will compare cross-sectional Alzheimer’s biomarkers between ADNI participants with and without MBI. These biomarkers may include CSF amyloid, tau, and phospho-tau, and imaging studies including global and regional SUVRs for amyloid PET and (if available) tau PET. 2.After completing these cross-sectional studies we plan to request data for longitudinal analyses, with those plans potentially dependent on the results of the cross-sectional analyses.
Additional Investigators