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Background for Primary Care Screening with the CANS-MCI

Screening for Mild Cognitive Impairment (MCI) and Alzheimer's Disease Risk

In the 1990s, the opinion was widely accepted in primary care that "detecting dementia in the pre-symptomatic (MCI) phase has no significant impact in illness outcome"(1). Since that time, a number of clinical interventions have shown promise as factors that delay the onset or progression of Alzheimer's Disease (AD) and Mild Cognitive Impairment (MCI). Sometimes, as is the case with hormone replacement therapy and metrifonate (2,4), the results first seem promising for primary care but the optimism is not supported by subsequent research. The most impressive interventions (with both theoretical and empirical bases for their efficacy) involve chemical agents such as cholinergic drugs or cholinesterase inhibitors [donepezil, rivastigmine](3,5), anti-inflammatory drugs (6), and antioxidants(7). Researchers widely acknowledge that the best opportunities for primary care treatment exist at the earliest stage of AD detection, before significant or irreversible brain damage has occurred(8). Therefore, efforts to target persons who have the highest risk of developing mild cognitive impairment (MCI) or Alzheimer's disease offer the best possible method to screen in primary care offices for the need to refer for intensive diagnostic evaluation and possible symptom retardation treatment. Presently, no widespread assessment of cognitive disorders is being performed in primary care, and early screening in primary care for MCI and Alzheimer's is often delayed until symptoms are relatively advanced(9).

Standardized neuropsychological tests of memory and other cognitive abilities offer early diagnostic markers for the disease (8,10,11,12,13,14,15). Linguistic ability deficits that are predictive of AD might even be measured many years before the onset of symptoms (17). However, AD is a progressive disorder whose symptoms change over time, and a variety of atypical expressions of the disease can be expected at pre-clinical (MCI) stages (18). Some mild AD patients score within the normal range on current standardized test measures but "have significant difficulties in the natural setting of their daily lives, such as driving, working, household chores and finances"(19).

Since there are marked individual differences in MCI symptom expression, it would be useful to establish baseline cognitive functioning levels in primary care facilities for each individual on several cognitive dimensions. Longitudinal re-testing in primary care facilities would be the most precise, economical method for early detection of the mild cognitive impairments that lead to AD. Screen, Inc. has developed a set of automated tests for that purpose. If you test someone repeatedly on these tests, a doctor can compare the progression of the scores and also compare the rates of deterioration to those of normal people the same age and to people later found to have been showing mild cognitive impairments predictive of dementia.

It is critical to administer tests in exactly the same way each time, so that measurements of change are accurate. Testing with a computer provides a method for standard administration without costly staff training and re-training. The ways that one interacts with the computer on the CANS-MCI touch screen tests were designed to parallel the most effective in-person methods that do not create anxiety. There is even a correspondence in errors that people make with effective computer-administered and profesional traditional administration methods (20,21,10,23,24).

Five types of cognitive tasks have proven to be strong and independent predictors of subsequent dementia of the Alzheimer's type: language fluency measured by the naming of pictured objects, the matching of designs with letters or numbers, memory acquisition over a number of trials with reminders (category hints) for words not recalled on previous trials, spatial relations (e.g. putting correct times on a clock face), and delayed recall of words recently learned (8,10,11,12,13,14,). These five tasks, plus tests of reaction time and of the ability to inhibit inappropriate responses (an important aspect of ability to function in the community), comprise the CANS-MCI test battery. They are realistic enough to capture some of the difficulties people experience in the natural setting of their daily lives (23). Remember, the CANS-MCI tests do not diagnose Alzheimer's Disease or MCI, they only provide the earliest possible way to help select people with mild cognitive impairments (MCI) who would benefit from more intensive diagnostic evaluation. They help people who need full PET(25) or neuropsychological evaluations get them through their primary care doctors early enough for maximum benefit from symptom-delaying or preventing treatments.* The tests measure the mild cognitive impairments that most often precede AD, but the CANS-MCI can also be administered in primary care settings to people who already have mild AD to track the effects of medications. Scores are placed in the context of age, education level, depression, alcohol use, and medications.

References:

  1. Zazove, P, Mehr, DR, Ruffin, MT, Klinkman, MS, Peggs, JF, and Davies, TC A Criterion-Based Review of Preventive Health Care in the Elderly. Journal of Family Practice, 34 (3), 320-347, 1992.
  2. Schneider, LS, Farlow, MR, Pogoda, JM & Poirier, J Interaction of Estrogen Replacement Therapy and Apolipoprotein E Genotype Status on Response to Cholinesterase Inhibitor Therapy in Alzheimer's Disease In Iqbal, K, Winblad,T, Nishimura, M, Takeda, M, & Wisniewski, HM (Eds.) Alzheimer's Disease: Biology, Diagnosis and Therapeutics, Wiley & Sons, New York, 1997.
  3. Sano, M, et al A controlled trial of selegline, apha-tocopherol, or both as treatment for Alzheimer's disease. New England Journal of Medicine, 336, 1216-1222, 1997.
  4. Schmidt, BH, Hinz, VC & van der Staay, FJ Cognition Enhancement by Metrifonate: Evidence from Animal Studies. In Iqbal, K, Winblad,T, Nishimura, M, Takeda, M, & Wisniewski, HM (Eds.) Alzheimer's Disease: Biology, Diagnosis and Therapeutics, Wiley & Sons, New York, 1997.
  5. Rogers, SL, Farlow, MR, Mohs, R, Friedhoff, LT, & the Donepezil Study Group. A 24-week, double-blind, placebo-controlled trial of donepezil in patients with Alzheimer's disease. Neurology, 50, 136-145, 1998.
  6. McGeer, PL, Schulzer, M, & McGeer, EG Arthritis and anti-inflamatory agents as possible protective factors for Alzheimer's disease: a review of 17 epidemioloogic studies. Neurology, 47, 425-432.
  7. Wengenack, TM, Curan, Gl, & Poduslo, JF Therapeutic Strategies for the Non-invasive Treatment of Alzheimer's Disease by Polyamine-modified Neurotrophic Factors and Antioxidant Enzymes with Increased Permeability at the Blood-Brain Barrier in Rats. In Iqbal, K, Winblad,T, Nishimura, M, Takeda, M, & Wisniewski, HM (Eds.) Alzheimer's Disease: Biology, Diagnosis and Therapeutics, Wiley & Sons, New York, 1997.
  8. Howieson, D.B., Dame, A., Camicioli, R., Sexton, G., Payami, H., and Kaye, J.A. Cognitive Markers Preceding Alzheimer's Dementia in the Healthy Oldest Old. Journal of the American Geriatrics Society, 45:584-589, 1997.
  9. Callahan, CM, Hendrie, HC, & Tierney, WM Documentation and evaluation of cognitive impairment in elderly primary care patients. Annals of Internal Medicine, 122, 422-429, 1995.
  10. Bondi, MW, Monsch, AU, Galasko, D, Butters, N, Salmon, DP & Delis, DC Preclinical Cognitive Markers of Dementia of the Alzheimer's Type. Neuropsychology, 8 (3), 374-384, 1994.
  11. Flicker, C, Ferris, SH and Reisberg, B A Two-Year Longitudinal Study of Cognitive Function in Normal Aging and Alzheimer's Disease. Journal of Geriatric Psychiatry and Neurology, 6, 1993, 84-96.
  12. Jacobs, DM, Sano, M, Dooneief, G, Marder, K, Bell, KL & Stern, Y. Neuropsychological detection and characterization of preclinical Alzheimer's disease. Neurology, 45, 957-962, 1995.
  13. Masur, DM, Sliwinski, M, Lipton, RB, Blau, AD & Crystal, HA Neuropsychological prediction of dementia and the absence of dementia in healthy elderly persons. Neurology, 44, 1427-1432, 1994.
  14. Petersen, RC, Smith, GE, Ivnik, RJ, Kokmen, E, & Tangalos, EG Memory function in very early Alzheimer's disease. Neurology, 44, 867-872, 1994.
  15. Tuokko, H, Vernon-Wilkinson, R, Weir, J, & Beattie, BL Cued recall and early identification of dementia. Journal of Clinical and Experimental Neuropsychology, 13, 871-879, 1991.
  16. Tierney, MC, Szalai, JP, Snow, WG, et al Prediction of Probable Alzheimer's disease in memory-impaired patients: a prospective longitudinal study. Neurology, 46, 661-665, 1996
  17. Snowdon, DA, Kemper, SJ, Mortimer, JA, Greiner, LH, Wekstein, DR 7 Markesbery, WR Linguistic Ability in Early Life and Cognitive Function and Alzheimer's Disease in Late Life. Journal of the American Medical Association, 275 (7) 528-532, 1996.
  18. Fabiszewski, KJ, Rheaume, YL, and Lasch, KE (Eds.) Clinical Management of Alzheimer's Disease, Aspen Pub., Rockville, MD, 1988. P 13-28.
  19. Reisberg, B, Schneck,MK, Ferris, SH, The Brief Cognitive Rating Scale (BCRS): Findings in primary degenerative dementia. Psychopharmacology Bulletin, 19, 47-50, 1983.
  20. Hodges, JR, Salmon, DP & Butters, N Semantic memory impairment in Alzheimer's disease: failure of access or degraded knowledge? Neuropsychologia, 30, 301-304, 1992.
  21. Flicker, C & Ferris, SH Implications of Memory and Language Dysfunction in the Naming Deficit of Senile Dementia. Brain and Language, 31, 187-200, 1987.
  22. Chertkow, H & Bub, D Semantic memory loss in dementia of Alzheimer's type. Brain, 113, 397-417, 1990.
  23. Sim, A & Sussman, I Alzheimer's disease: Its natural history and differential diagnosis. Journal of Nervous and Mental Disorders, 135, 489-499, 1962.
  24. Solomon, P.R., Hirschoff, A., Kelley, B., Relin, M., Brush, M, DeVeaux, R. & Pendlebury, W.W. A 7 Minute Neurocognitive Screening Battery Highly Sensitive to Alzheimer's Disease. Archives of Neurology, 55, 349-355, 1998.
  25. Jane B. Tornatore, PhD, Emory Hill, PhD, Jo A. Laboff, MSW, Brian Fogel Preliminary Screening for Mild Cognitive Impairment: Using the CANS-MCI in Primary Care to Determine Need for Imaging. 9th International Conference on Alzheimer's Disease, Philadelphia, PA, July, 2004.

* Example: A 52-year old professional took the CANS-MCI 3 times. The first time his memory, executive functions, and fluency factor scores were all above the 80th percentile for highly educated people. The second time (one year later) his memory factor score was in the 65th percentile, but the other factor scores were above the 80th percentile. He was asked to return for a third testing 3 months later. At the third testing, his memory was at the 52nd percentile, still above average for highly educated people. However, the decline flagged a recommendation for a full neuropsychological evaluation. That evaluation took place 1 month later and resulted in a diagnosis of MCI. It also resulted in immediate treatment. Within one year that MCI diagnosis had been changed to Probable Alzheimer's Disease.

Screen, Inc., Seattle, WA
The Computer-Administered Neuropsychological Screen for Mild Cognitive Impairment
(The CANS-MCI) research@screen-inc.com

 
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