Predicting Dementia of the Alzheimer Type Using Cognistat

Matthew Battista, PhD, Siobhan O’Toole, PhD, Stephanie Gaudenti, PhD, Nick Tolchin, MA, Jeff Delarm, MA, and Alycia Barlow, MA

Although not as extensively studied or widely used as the Mini Mental State Examination, Cognistat may be a more sensitive tool for cognitive evaluation in elders. These investigators propose Cognistat subscale cutoff scores for differentiating DAT from other types of cognitive impairment in veterans.

ementia is a generic term mentia is and increasingly will be a tions for both clinical care and future used to characterize the de- major health problem for our aging research, we conducted a study to velopment of multiple cogni- society, including our veteran popu- develop Cognistat cutoff scores that Dtive deficits that impair such lation. would maximally differentiate DAT intellectual abilities as language, ab- Cognistat, also referred to as the from other forms of cognitive im- stract reasoning, and memory, while Neurobehavioral Cognitive Status pairment in a veteran population. In affecting a person’s relational or occu- Examination, is a testing instru- completing this analysis, our overall pational functioning. Dementia can ment used to screen for and differ- goal was to help establish a demen- be caused by a number of physiologi- entiate between a variety of cognitive tia-specific “fingerprint” that practi- cal conditions, including neurode- disorders, including dementia.3–8 It tioners could further use to identify generative, vascular, traumatic, toxic, provides basic information about a those veterans in need of a more or infectious etiologies. patient’s executive system function- comprehensive evaluation. Dementia of the Alzheimer type ing (through measures of attention (DAT) is the most common form of and abstract reasoning), as well as COGNISTAT AS A SCREENING dementia and is characterized as a information on domains character- TOOL progressive neurodegenerative pro- istically affected by dementia. Cog- Cognistat evaluates five major do- cess, with age identified as the single nistat has been identified as a useful mains of cognitive functioning— most important risk factor.1 A recent instrument in screening for cognitive language, construction, memory, report compiled by the VA’s Office of impairment in elderly inpatient and calculation, and reasoning abilities— the Assistant Deputy Under Secretary outpatient populations, including and, with separate measures, assesses for Health projected that the preva- those with dementia or dementia-like levels of consciousness, orientation, lence of dementia in veteran enroll- symptoms.7,9 and attention. The 25-minute screen- ees aged 65 and older will rise from Studies have suggested that Cog- ing test generates a profile of cogni- 218,455 in 2004 to a peak of 339,248 nistat profiles also can be used to dif- tive abilities, rather than one global in 2015—a remarkable 55% increase ferentiate between various cognitive score,11,12 and it is designed so that in just over a decade.2 Therefore, de- disorders. For example, Margolin and a patient’s successful performance in colleagues suggested that patients several cognitive domains does not

Dr. Battista is a neuropsychologist at the VA with Parkinson disease have signifi- obscure deficits in others. The scor- Central California Health Care System, Fresno. cantly different Cognistat profiles ing system calculates values, rang- Dr. O’Toole is an assistant professor at the than patients with DAT.10 In addition, ing from 0 to 12, for each cognitive California School of Professional Psychology (CSPP) at Alliant University, Fresno. Dr. Gaudenti the authors of Cognistat provided domain. Memory domain scores, is a psychologist in the U.S. Air Force and is case studies depicting the profiles for instance, are based on the un- stationed overseas. At the time of this writing, associated with various cognitive prompted, delayed recall of four ev- Mr. Tolchin was a psychology intern at CSPP. 11 13 He is currently a psychology intern at Lakeview disorders, though there is little sys- eryday words. Specialty Hospital and Rehabilitation Center, Wa- tematic research regarding the deriva- Data on normal Cognistat values terford, WI. Mr. Delarm is a data consultant in tion of these profiles. have been developed for a variety of Weld County, CO. Ms. Barlow is a psychology 14 intern at the John D. Dingell VA Medical Center, Since screening for dementia is as populations, including children, 11 15,16 Detroit, MI. important as ever, having implica- healthy adults, healthy elders,

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and neurosurgery patients.17 Data from healthy elders and neurosurgery Table 1. Initial and final, adjusted Cognistat patients suggest age-specific de- cutoff scores determined to maximize sensitivity clines in memory and construction for dementia of the Alzheimer type ability.15,16 Several studies have shown that Cognistat domain Initial score Final, adjusted score Cognistat has good sensitivity and Orientation < 12 < 11 specificity in predicting organic brain Attention > 5 > 4 impairment18 and moderate overall validity in screening for cognitive im- Comprehension > 4 > 2 pairment.19 Other studies have sug- Repetition > 9 > 7 gested that it has good sensitivity but Naming 5–8 (inclusive) 3–8 (inclusive) relatively lower specificity than other Construction 1–5 (inclusive) 0–5 (inclusive) screening measures.13,20,21 Compared to the Mini Mental Memory < 6 < 6 State Examination (MMSE),22 the Calculation > 1 > 1 most widely used cognitive screen- Similarities 3–8 (inclusive) 2–8 (inclusive) ing test, Cognistat has been found to Judgment > 3 > 2 have a higher sensitivity in geriatric populations, specifically for orienta- tion and memory.21 In addition, Cog- Establishing the DAT and disorders included vascular demen- nistat’s individual scores for a variety Non-DAT 1 patient groups tia, mild cognitive impairment, and of cognitive domains provide more During the first phase of our research, Parkinson disease.) The patients’ av- information about particular areas of we established our DAT group. These erage age was 66.9 years (range, 25 to possible cognitive decline than the 20 patients had been diagnosed with 79 years), all were male, and all had one overall score of the MMSE, which DAT, using criteria from either the been referred for routine neuropsy- may obscure deficits in specific cogni- Diagnostic and Statistical Manual of chological evaluations. The average tive domains. Mental Disorders, Fourth Edition or years of education for the group was the National Institute of Neurological 12.3 (range, five to 15 years). STUDY DESIGN and Communicative Disorders and Only patients who had MMSE To identify Cognistat subscale cutoff the Stroke-Alzheimer’s Disease and scores greater than 20 (indicating scores for dementia, we retrospec- Related Disorders Association. This overall mild or moderate cognitive tively evaluated the Cognistat profiles group included only patients diag- impairment) were included in the of veterans diagnosed with DAT and nosed with DAT who had no addi- DAT group and the non-DAT 1 group, those diagnosed with other forms of tional psychiatric disorders or other because more advanced stages of de- cognitive impairment. Testing proto- neurologic diagnoses. The average mentia are associated with significant cols were selected randomly from neu- age of these patients was 78.2 years impairment across multiple areas, and ropsychological assessment cases (range, 67 to 87 years). The group such deficits in performance would at the VA Central California Health consisted of 20 patients, 16 men be below the lower limit of inclusive Care System’s Fresno psychology sec- and four women, and all had been Cognistat scores. tion. Cognistat was administered as referred for routine neuropsychologi- part of a standard neuropsychological cal evaluations. The average years of Identifying the subscale cutoff evaluation, and diagnoses were made education for these group members scores as part of routine assessments during was 11.1 (range, seven to 14 years). Next, we established Cognistat sub- which other patient data (such as ad- We then established our non-DAT scale criterion scores that would ditional cognitive measures, medical 1 group by selecting 20 patients who maximally distinguish the DAT group history, and behavioral observations) did not meet the criteria for DAT but from the non-DAT 1 group patients. were considered as well. All testing who had been diagnosed, through the Our initial cutoff scores for each do- was administered by graduate level MMSE, with mild to moderate forms main were derived a priori, based on psychology students. of other cognitive disorders. (These clinical experience.

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Because early-stage DAT typically mine their individual contributions differentiating DAT from other types presents with disproportionate mem- to group differentiation. of cognitive impairment in veterans, ory impairment and only mild overall are consistent with previously pub- cognitive deficit, we chose memory RESULTS lished research. In addition, our data and orientation domain cutoffs to se- Using the non-DAT 2 and the DAT revealed strong specificity and a high lect for low scores, or those ranging study groups, a chi-square test for positive predictive value, suggesting toward the lower limit. We devised independence was used to assess that the use of cutoff scores derived cutoffs for other measures to select whether the established Cognistat from clinical experience improved for scores ranging toward the upper cutoff scores could predict DAT ac- the sensitivity and predictive valid- limit. We entered the cutoff scores curately. None of the cell sizes had ity of Cognistat. This relatively im- into a database that assigned study a minimum expected count of less pressive result may have been due to participants to either the DAT or the than five. The Pearson chi-square test the small sample size or the inclusion non-DAT 1 group, and by successive results were significant (χ2 [1, n = 40] of only male veterans who had been adjustments of cutoffs, we maximized = 17.3, P < .01). The levels of sensi- suspected of having cognitive failure. the specificity and sensitivity of the tivity and specificity reached using Despite limitations in our meth- cutoff scores (Table 1). the cutoff scores were 75% and 90%, odology, however, our data nonethe- respectively (Table 2). The positive less provide compelling evidence The age-matched non-DAT predictive value, or the likelihood of that Cognistat is worth studying as group a patient actually having DAT given a a dementia-specific, brief cognitive During the second phase of our re- positive result, was 88%. examination tool. The multiple and search, we established a second con- The single Cognistat domain cut- quantifiable subtests (some of which trol group—the non-DAT 2 group. off that showed the greatest ability to have age-corrected normative data) We selected members of this group using the same criteria as the non- Table 2. Classification of study patients as having or not DAT 1 group, except that non-DAT having DAT* using the established Cognistat cutoff scores 2 group members were age-matched (within 12 months) to the members Group assignment† of the DAT group. The non-DAT 2 group consisted of 20 participants Study group Patients with DAT Patients without DAT with an average age of 78.2 years DAT group (n = 20) 15 (75%) 5 (25%) (range, 67 to 87 years). All partici- Non-DAT 2 control 2 (10%) 18 (90%) pants were male and had been re- group (n = 20) ferred for routine neuropsychological evaluation. These group members *DAT = dementia of the Alzheimer type. †χ2 (1, n = 40) = 17.29, P < .01. had an average of 10.7 years of edu- cation (range, six to 18 years). differentiate correctly between DAT and differential profile generated Our final step was to assess the and non-DAT 2 patients was memory. across patient groups holds particu- utility—including specificity, sensitiv- The memory domain alone produced lar promise. In our current research, ity, and positive predictive value—of a significant chi-square value (χ2 [1, n specifically setting the memory and our established Cognistat subscale = 40] = 21.5, P < .01), and it achieved orientation domain subtest cutoffs criterion scores on members of the 100% sensitivity (Table 3). Using the toward the low end of the scoring non-DAT 2 group. We used the ad- memory domain cutoff alone, how- scale is consistent with the pattern of justed Cognistat cutoff scores to as- ever, resulted in much lower speci- cognitive deficits typically associated sign the DAT and non-DAT 2 group ficity and positive predictive values: with early-stage DAT. Indeed, this is participants into DAT and non-DAT 70% and 77%, respectively. demonstrated in our impressive find- groups. We then determined the ing that, when using the Cognistat specificity, sensitivity, and positive GOOD SENSITIVITY DESPITE memory subtest cutoff scores alone, predictive value of these cutoff scores. LIMITATIONS sensitivity was perfect and overall pre- Individual items from the Cognistat Our results, which suggest that Cog- dictive value was fair. In other words, were examined post hoc to deter- nistat has fairly good sensitivity in Cognistat appears to be potentially

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tion: A brief but quantitative approach to cognitive Table 3. Classification of study patients as assessment. Ann Intern Med. 1987;107:481–485. 12. Mueller J, Kiernan R, Langston W. Manual for Cog- having or not having DAT* using the established nistat (Neurobehavioral Status Exam; NCSE). Fair- fax, CA: The Northern California Neurobehavioral Cognistat memory domain cutoff alone Group Inc. Oakley; 2001. 13. Schwamm LH, Van Dyke C, Kiernan RJ, Merrin EL, Group assignment† Mueller J. The Neurobehavioral Cognitive Status Examination: Comparison with the Cognitive Ca- Study group Patients with DAT Patients without DAT pacity Screening Examination and the Mini-Mental State Examination in a neurosurgical population. DAT group (n = 20) 20 (100%) 0 (0%) Ann Intern Med. 1987;107:486–491. 14. Wuethrich J, Lebby P, Ammen S, Canfield M. A Non-DAT 2 control 6 (30%) 14 (70%) Normative and Validational Analysis of Child and Adolescent Performance on the Cognistat [disserta- group (n = 20) tion]. Fresno, CA: California School of Professional Psychology; 1998. † 2 *DAT = dementia of the Alzheimer type. χ (1, n = 40) = 21.5, P < .01. 15. Eisenstein N, Engelhart CI, Johnson V, Wolf J, Williamson J, Losonczy MB. Normative data for healthy elderly persons with the neurobehavioral useful in producing dementia-specific Please review complete prescribing in- cognitive status exam (Cognistat). Appl Neuropsy- chol. 2002;9:110–113. patterns, at least for DAT. formation for specific drugs or drug 16. Macaulay C, Battista M, Lebby PC, Mueller J. Ge- combinations—including indications, riatric performance on the Neurobehavioral Cog- nitive Status Examination (Cognistat). What is SUGGESTIONS FOR FUTURE contraindications, warnings, and ad- normal? Arch Clin Neuropsychol. 2003;18:463–471. RESEARCH verse effects—before administering 17. Cammermeyer M, Evans JE. 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