Neurobehavioral Manifestations

All ADNI CN and MCI participants were diagnostically reclassified using Jak/Bondi actuarial neuropsychological test methods [24 (link), 25 (link)] applied to their baseline data. Six neuropsychological measures from ADNI were chosen because of their routine use in assessing early cognitive manifestations of AD and administration across all three ADNI grant periods (ADNI-1, -GO, and -2). The six measures were Category Fluency and Boston Naming Test scores for the language domain, Trail-Making Test Parts A and B scores for the graphomotor speed/executive function domain, and Rey AVLT delayed recall and delayed recognition scores for the episodic memory domain. None of these cognitive measures were used in making the initial ADNI diagnostic classification. Each measure was converted to an age-corrected standard score using published normative data: Mayo Older Americans Normative Study data (n = 530; [36 ]) for the Rey AVLT and National Alzheimer’s Coordinating Center normative data (n = 3,286; [37 (link), 38 (link)]) for the remaining neuropsychological measures. Participants were considered to have MCI if any one of the following three criteria were met: 1) they had an impaired score, defined as >1 SD below the age-corrected normative mean, on both measures within at least one cognitive domain (i.e., memory, language, or speed/executive function); 2) they had one impaired score, defined as >1 SD below the age-corrected normative mean, in each of the three cognitive domains sampled; or 3) they had a score on the FAQ =9 indicating dependence in three or more daily activities. This latter criterion approximated Jak, Bondi et al.’s [25 (link)] incorporation of instrumental ADL assessment to diagnosis and reflects significant study partner-rated difficulties in everyday function. If none of these criteria were met, the participant was diagnosed as CN.

First, existing screening and diagnostic instruments for ICDs and other compulsive behaviors that have been used in PD and the general population were reviewed(1 ;6 (link);19 (link);21 (link)–23 (link)). Second, input was solicited from outside experts in the area of ICDs in PD (MNP, JM, and VV) and from an expert in questionnaire development (JAS). Third, a preliminary ICD section of the QUIP was structured to be consistent with diagnostic criteria or defining clinical characteristics as described in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR)(1 ). This consisted of an introductory question and four additional questions that addressed cognitive symptoms, affective symptoms, lack of ability to reduce or stop the behaviors, and activities that enable continuation of the behaviors. The compulsive medication use section was modeled on both Giovannoni’s proposed criteria for hedonistic homeostatic dysregulation and DSM-IV substance dependence criteria. While minor wording changes were made in subsequent drafts, the structure of these sections remained consistent throughout the instrument development process. The other compulsive behaviors section was designed with conciseness in mind (an introductory question for each of the three behaviors plus two common additional questions). Guiding principles in the design of the QUIP included making it self-administered, brief yet comprehensive, and consistent in wording across different ICDs and other compulsive behaviors.
Next, the preliminary QUIP was administered to a sample of healthy controls (10 research staff members who work with neurodegenerative disease and psychiatric populations), and modifications were made based on the feedback received. Finally, the QUIP was administered to five PD patients and their informed others, and additional modifications were made based on the feedback received from them.
The final version that was validated queried about behaviors that occurred at any time since the onset of PD (either inactive or active) that lasted at least four weeks. We chose the time frame of “anytime during PD” due to the observation that a substantial number of PD patients who have experienced an ICD during PD are currently asymptomatic due to clinical management, but may be at elevated risk of developing an ICD in the future. Another version of the QUIP that queries only about active behaviors is also available; it is identical to the validated version except for the time frame queried. The final version of the QUIP is divided into three sections: (1) five questions (including an introductory question that defines and gives examples of problem behaviors) for the four ICDs reported in PD; (2) three distinct introductory questions and two common additional questions for hobbyism, punding, and walkabout; and (3) five questions (including an introductory question) for compulsive medication use. The Flesch-Kincaid Readability Test assessed the QUIP to require a 12^th grade reading level.