Supplementary Appendix This appendix has been provided by the authors to give readers additional information about their work. Supplement to: Budson AE and Price BH. Memory Dysfunction in Clinical Practice. N Engl J Med 2005; 352:xxxx-xx.
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Web supplement to “Memory dysfunction,” by Andrew E. Budson, M.D. and Bruce H. Price, M.D.
There are many cognitive tests that can be used to assess a patients’ episodic memory function. We discuss several here that we have found to be useful in our clinical practice. The clinician interested in details of administration or validation of these tests in different populations is encouraged to follow-up with the references provided or a neuropsychology textbook such as that by Lezak.57 There are many other excellent cognitive tests that are not mentioned here; omission does not imply that other tests are any less valuable than those that are discussed. Relationships between a patient’s cognitive functions, test performance, and their “real-life” activities are often complex. Test performance is rarely pathognomonic. No single test is capable of evaluating all aspects of memory. Possible factors confounding test interpretation include aphasia, dyslexia, low intellectual function, alterations in mood and motivation, confusion or delirium, psychosis, and medication side-effects.
The Mini-Mental State Examination Published by Folstein, Folstein, and McHugh in 1975,18 the Mini-Mental State Examination (MMSE) is one of the most widely used tests in clinical medicine for assessing a patient’s overall cognitive function. A revised version is now available, published by Psychological Assessment Resources, Inc. (Lutz, Florida); more information about it is available on-line at www.minimental.com.
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The advantages of the MMSE include that it is well known, easy to administer in about five to ten minutes, that it samples a number of cognitive functions, and has testretest and interrater reliabilty. A limitation is that only three words are to be remembered on the recall test, making the MMSE insensitive for patients with mild but clinically relevant memory problems. Another limitation is that the interval between registration and recall is not standard; instead, it is dependent upon the time it takes for the patient to perform the attention and calculation section. Thus, patients who take a long time to complete the attention and calculation section will end up with a more difficult memory test compared with those who complete the attention and calculation section more quickly. The MMSE evaluates episodic memory in a number of ways. The “Registration” section tests encoding. Although it is not used in scoring, the number of trials needed to register the three objects provides information on how easily the patient is able to encode information. Assuming registration is eventually achieved, performance on the “Recall” section may be impaired by either a failure to retain the information (e.g., due to medial temporal lobe dysfunction) or by a failure to access that information (e.g., due to frontal lobe dysfunction). Episodic memory is also required to answer most of the orientation questions. Numerous studies have evaluated the MMSE in the last 30 years. When using the MMSE as a screening instrument for cognitive dysfunction, we favor stringent cut-offs with the understanding that a result below this number does not definitively indicate dementia or other cognitive impairment, but suggests that a more thorough evaluation is warranted. Scores which warrant concern are those below 29 for adults younger than 50
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years of age, below 28 for those from 50-79 years of age, and below 26 for those from 80-89 years or age.58 In addition to age, lower levels of education are also associated with lower scores in the absence of cognitive impairment. When reporting the results of the MMSE, we encourage clinicians to report which items were missed in addition to the total score. The implications of scoring 26 out of 30 may be very different depending upon which items are missed. For example, a patient who misses all three of the recall items and the date shows evidence of episodic memory dysfunction, whereas the patient who misses four points on the attention and calculation section does not.
The Blessed Dementia Scale In 1968 Blessed, Tomlinson and Roth published a study that correlated the number of senile plaques in several areas of the cortex of the brain in dementia patients with a quantitative measure of dementia severity which they called the Dementia Scale.19 Now known as the Blessed Dementia Scale (BDS; see below), it thus has the advantage of reflecting the extent of pathology when administered to patients with Alzheimer’s disease. It has the disadvantage of being developed and used mainly for patients with or at risk for dementia, and not other etiologies of memory impairment. A major advantage of using the BDS is that it is comprised of two subtests, which can be administered together or separately. The first is a caregiver scale which is informative regarding the patient’s activities of daily living and personality. This caregiver scale can be used in patients with mild, moderate, or severe impairment. The
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second is the “Information-Memory-Concentration test” which is administered to the patient. Episodic memory is evaluated on the Information-Memory-Concentration test by the “5-Minute Recall” section and most questions on the “Information” section. By contrast, the “Personal Memory” and “Non-personal Memory” sections sample remotely learned information which is part of semantic memory. Note that the number of impaired responses (or errors) are commonly reported for the BDS, rather than the number of unimpaired (or correct) responses. Thus, the most severely demented patient would score 28 on the caregiver scale and 37 on the Information-Memory-Concentration test. For the caregiver scale, scoring less than 4 suggests that the patient is unimpaired; a score from 4 to 9 suggests mild impairment; scores higher that 10 suggest moderate to severe impairment.59 For the InformationMemory-Concentration test, less than 4 errors suggests no impairment, 4 to 10 errors suggests mild impairment, 11 to 16 errors suggests moderate impairment, and greater than 16 errors suggests severe impairment.60 As with the MMSE, when reporting the results of the BDS, we encourage clinicians to report which items were missed in addition to the total score.
The 7 Minute Screen Like the BDS, the 7 Minute ScreenTM (7MS; see below) was also developed for use in dementia. In 1998 Solomon and colleagues published the first report of a screening assessment they developed consisting of four subtests: Orientation (month, date, year, day, time), Memory (16 items, 4 at a time, cued and uncued), Clock Drawing,
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and Verbal Fluency (naming animals in one minute).21 Unlike most tests, however, the interpretation is performed automatically by entering the result of the four subtests into a special calculator or web site (http://www.memorydoc.org), leading to a high or low probability that the patient has Alzheimer’s disease. The calculated formula is based upon the results of a logistic regression comparing sixty patients with Alzheimer’s disease and sixty healthy control subjects. The 7MS demonstrates sensitivity, specificity, test-retest reliability, and interrater reliability all greater than 90%. The test has been validated in the primary care setting as a screening tool for patients over the age of sixty,61 and it has also been validated in other languages.62,63 Advantages of this test include that it is sensitive, reliable, easy to administer, takes little time, and the interpretation is performed automatically. Another advantage of the 7MS is that both episodic and semantic memory are evaluated, episodic memory by the Orientation and Memory subtests and semantic memory by the Verbal Fluency subtest. Limitations include that it has been developed for and used in patients with or at risk for dementia, and that a calculator is needed for interpretation. If the result from the calculator reads “HI”, the patient has a high probability of dementia characteristic of Alzheimer’s disease, and it is suggested that the patient undergo a full diagnostic evaluation. It is cautioned (and we agree) that it is inappropriate to diagnose Alzheimer’s disease based only on the results of the 7MS. If the calculator reads “LO”, the patient has a low probability of dementia characteristic of Alzheimer’s disease; in this circumstance the patient may or may not need further evaluation depending upon the history and clinical setting. In less than 5% of cases the calculator may also indicate that the data are insufficient to make a judgment; in this
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situation either using other evaluation measures or re-screening the patient in 6 to 9 months would be appropriate.
Other tests Although the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) word list memory, recall, and recognition test was developed in part for research studies, it has become one of the standards of care in clinical centers that diagnose Alzheimer’s disease and other dementias.20 It consists of ten words to be remembered which are repeated over three study-test trials, a ten minute retention interval, a delayed recall test, and finally a twenty-word recognition test (ten studied and ten unstudied words). There are several advantages to using this CERAD memory test. Because separate scores are obtained for the encoding trials, delayed recall, correct recognition, and false positive responses, it facilitates separating out performance on these different aspects of episodic memory. Clinicians who are interested in using the CERAD memory test can learn more about it and order materials from the CERAD web site, http://cerad.mc.duke.edu.
The Drilled Word Span procedure,2,64 a useful bedside memory test, can be briefly described as follows. First, the patient’s digit span (how many single digit numbers they can repeat) is measured. Then, they are asked to memorize a list of words equal to one less than the patient’s digit span. (For example, if their digit span is seven they are given six words to remember.) The patient then recites the words back to the examiner, and the process is repeated until the patient can recite the list correctly three consecutive times.
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Recall is tested after one minute without distraction. (If the entire list is not recalled, it is drilled again.) Recall is then tested after one minute with distraction, and then after three minutes with distraction. Many clinicians also find it useful to test recall after ten minutes with distraction. Finally the patient undergoes multiple choice testing with an equal number of foils. Advantages of this test include that it takes into account the patient’s level of attention, that the rate of forgetting between one and three minutes can be measured, and that recall can be contrasted with recognition. For more information consult the references below2,64 or contact Sandra Weintraub, PhD, Cognitive Neurology and Alzheimer’s Disease Center, Northwestern University Medical School, 320 E. Superior, Searle 11-467, Chicago, IL 60611 USA,
[email protected].
The Three Words-Three Shapes memory test is another useful bedside test, and one which can evaluate verbal and nonverbal memory, both in the visual modality.2,64,65 Patients are shown three shapes with one word underneath each shape. There is an incidental encoding trial, followed by drilling the items using study-recall trials until five of the six items are recalled or five trials have been given. Delayed recall is tested at 5, 15, and 30 minutes, and multiple choice recognition is tested after the 30 minute recall test. This test is particularly useful when there is reason to suspect impaired memory for nonverbal materials that may be missed on a word-based memory test alone, or when trying to detect dementia in a patient with an aphasia or other language difficulty. For more information consult the references below;2,64,65 testing materials may be obtained from Sandra Weintraub, PhD, address listed above.
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Another approach to evaluate memory and other cognitive abilities is to use an informant based questionnaire. Such questionnaires rely on family members or close friends to evaluate the patient’s cognitive abilities. They have several advantages over clinician-administered instruments: they require little or no staff time, do not require the cooperation of the patient, and can be administered via mail, telephone or the internet. A recent example is the Alzheimer’s Disease Caregiver Questionnaire (ADCQ).66 The ADCQ consists of 18 yes/no questions evaluating memory, confusion and disorientation, geographic disorientation, reasoning and judgment, language abilities, and behavior that can be used to screen for Alzheimer’s disease. The ADCQ can be completed using a paper version or on line at www.ADCQ.net. The questionnaire is scored via the web site or computer software, and a report is generated which summarizes the cognitive deficits endorsed, whether the results are suggestive of Alzheimer’s disease, and recommendations and resources for the caregiver. The ADCQ is published by Psychological Assessment Resources, Inc. (Lutz, Florida, www.parinc.com).
References 2. Mesulam M-M. Principles of Behavioral and Cognitive Neurology. 2nd ed. New York, NY: Oxford University Press, 2000. 18. Folstein MF, Folstein SE, McHugh PR. A practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research 1975; 12:189-198. 19. Blessed G, Tomlinson BE, Roth M. The association between quantitative measures of dementia and of senile change in the cerebral grey matter of elderly subjects. Br J Psychiatry 1968; 114:797-811.
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20. Welsh KA, Butters N, Mohs RC, Beekly D, Edland S, Fillenbaum, Heyman A. The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part V. A normative study of the neuropsychological battery. Neurology 1994; 44:609-614. 21. Solomon PR, Hirschoff A, Kelly B, Relin M, Brush M, DeVeaux RD, Pendlebury WW. A 7 minute neurocognitive screening battery highly sensitive to Alzheimer’s disease. Arch Neurol 1998; 55(3):349-55. 57. Lezak MD. Neuropsychological Assessment. 3rd ed. New York: Oxford University Press, 1995. 58. Bleecker ML, Bolla-Wilson K, Kawas C, Agnew J. Age-specific norms for the minimental state exam. Neurology 1988; 38:1565-1568. 59. Eastwood MR, Lautenschlaeger E, Corbin S. A comparison of clinical methods for assessing dementia. J Am Geriatr Soc 1983; 31:342-347. 60. Locascio JJ, Growdon JH, Corkin S. Cognitive Test Performance in Detecting, Staging, and Tracking Alzheimer's Disease. Arch Neurol 1995; 52:1087-1099. 61. Solomon PR, Brush M, Calvo V, Adams F, DeVeaux RD, Pendlebury WW et al. Identifying dementia in the primary care practice. Int Psychogeriatr 2000; 12(4):483-493. 62. Tsolaki M, Iakovidou V, Papadopoulou E, Aminta M, Nakopoulou E, Pantazi T, Kazis A. Greek validation of the seven-minute screening battery for Alzheimer’s disease in the elderly. Am J Alzheimers Dis Other Dement. 2002; 17:139-148. 63. Meulen EFJ, Schmand B, van Campen JP, de Koning SJ, Ponds RW, Scheltens P, Verhey FR. The seven minute screen: a neurocognitive screening test highly sensitive to various types of dementia. J Neurol Neurosurg Psychiatry 2004; 75:700-705.
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64. Weintraub S. Mental state testing. In Samuels MA, Feske S, eds, Office Practice of Neurology, 2nd Edition. New York: Churchill Livingstone Inc., Chapter `35, pp 850-858, 2003. 65. Weintraub S, Peavy GM, O’Connor M, Johnson NA, Acar D, Sweeney J, Janssen I. Three words-three shapes: A clinical test of memory. J Clin Exp Neuropsychology 2000; 22:267-278. 66. Solomon PR, Murphy CA. The Alzheimer’s Disease Caregiver Questionnaire (ADCQ). Tampa, FL, Psychological Assessment Resources., 2002.
BLESSED DEMENTIA SCALE CAREGIVER SCALE
BLESSED DEMENTIA SCALE INFORMATION-MEMORY-CONCENTRATION TEST
NAME _______________________________________
DATE ________________________ No. _______________ (Ask patient to remember the name & address in the 5-Minute Recall section.)
CHANGES IN PERFORMANCE OF EVERYDAY ACTIVITIES Inability to perform household tasks ...................... Inability to cope with small sums money ................ Inability to remember a short list of items ............... Inability to find way about indoors ......................... Inability to find way about familiar street ................. Inability to interpret surroundings ............................ (e.g. to recognize whether in hospital or home) Inability to recall recent events ............................... (e.g. recent outings, relatives visits etc.) Tendency to dwell in the past .................................
0 0 0 0 0 0
.5 .5 .5 .5 .5 .5
0 .5 1 0 .5 1
CHANGES IN HABITS Eating: cleanly with proper utensils ....................... messily with spoon only .........................… simple solids (no utensils) ....................... has to be fed .........................................…
0 1 2 3
Dressing: unaided ................................................ occasionally misplaced buttons ............. wrong sequence, forgets items .............. unable to dress ....................................
0 1 2 3
Sphincter Control: Complete ................................. Occasionally wets bed .............. Frequently wets bed .................. Doubly incontinent ....................
0 1 2 3
INFORMATION Name .........................................................… Age .............................................................… Time (hour) ...............................................… Time of day .................................................. Day of Week ................................................. Date ............................................................... Month ............................................................ Season ......................................................... Year ............................................................. Place: Name .............................................. Street .............................................. Town ...............................................
0 0 0 0 0 0 0 0 0 0 0 0
1 1 1 1 1 1 1 1 1 1 1 1
Type of Place (e.g. Hospital, home etc.) ....... Recognition of persons ..................................
0 1 0 1 2
PERSONAL MEMORY Date of Birth ................................................. Place of Birth ................................................ School Attended ............................................ Occupation ................................................... Name of sibling or spouse ............................. Name of any town where patient worked ...…. Name of employer .....................................…..
0 0 0 0 0 0 0
1 1 1 1 1 1 1
0 0 0 0
1 1 1 1
NON-PERSONAL MEMORY
CHANGES IN PERSONALITY Increased rigidity ..........................................……. Increased egocentricity .................................…… Impairment of regard for feelings of others ....…… Coarsening of affect ...................................… Impairment of emotional control ....................…….. (e.g. increased petulance and irritability) Hilarity in inappropriate situations ..................……. Diminished emotional control ........................ (e.g. depression) Sexual misdemeanor (de nova in old age) .....……
1 1 1 1 1 1
0 0 0 0 0
1 1 1 1 1
0 0
1 1
0
1
Dates of WWI (1914-1918) ......................... Dates of WWII (1939-1945) ......................... President of the United States ........................ Vice President of the United States ................ 5-MINUTE RECALL (Mr.) John Brown ........................................ 42 West (Street) ........................................ Cambridge, (MA) .........................................
0 1 2 0 1 2 0 1
CONCENTRATION CHANGES IN INTEREST AND DRIVES Hobbies relinquished ....................................... 0 Diminished initiative or growing apathy ........... 0 Purposeless hyperactivity ..............................…….. 0
LEFT SCORE _________________
1 1 1
Months Backwards ...................................……. 0 1 2 Counting 1-20 ...................................…… 0 1 2 Counting 20-1 ...................................…… 0 1 2
RIGHT SCORE _______________
(Prepared by Dorene M. Rentz, Psy.D. and Andrew E. Budson, M.D. after Blessed, Tomlinson & Roth, 196818.)
Blessed Dementia Scale (BDS) Administration and Scoring Notes:
There is no agreed upon standard scoring of the BDS. These notes represent our suggestions for administration and scoring, using information from the original paper and the literature when possible. Note that the number of impaired responses [or errors] are commonly reported for the BDS, rather than the number of unimpaired [or correct] responses. Thus, 0 indicates normal performance or a correct response. The Caregiver Scale is for the clinician to administer to a caregiver (typically a relative or a nurse). Questions should be asked tactfully. For those items which may be scored 1, .5, or 0, total incompetence in an activity should be given a score of 1, and partial, variable, or intermittent incapacity should be given a score of .5. The Information-Memory-Concentration test is for the clinician to administer to the patient. If the patient is asked to memorize the name and address for the “5-Minute Recall” section first, it will be about 5 minutes by the time that section of test is reached (although it is better if timed). We recommend that the name and address to be remembered is repeated until the patient learns it (or up to 5 attempts). For the “Information” section, the patient must be within one hour for the “Time (hour),” and within one day for the “Date.” Similarly, no errors are scored if the patient gives a month that is correct within one day, or a season that is correct within one week. “Recognition of persons” is for the persons that they came with; if they came with two persons there is one possible error for each, and if they came with only one person there is only one possible error. Check the “Personal Memory” data with the caregiver or previous testing. For “Dates of WWI” and “Dates of WWII,” ask the patient for any of the years that these wars took place; a single correct year is sufficient. (Note that “Dates of WWI” is an outdated question that is of little value, now typically reflecting semantic knowledge that may have been learned in school rather than remote “NonPersonal Memory.”) For the “Concentration” section, score one error for one mistake, and two errors for two or more mistakes. Note that a number of the items, including “President,” “Vice President,” and the name and address of the “5-Minute Recall” section should be altered if necessary to reflect the patient’s cultural and regional knowledge.
