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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 patients 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 patients 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 test-
retest 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 Alzheimers
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 patients 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 Information-
Memory-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 Alzheimers disease. The calculated formula is based
upon the results of a logistic regression comparing sixty patients with Alzheimers
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 Alzheimers 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 Alzheimers disease based only on the results of the 7MS. If
the calculator reads LO, the patient has a low probability of dementia characteristic of
Alzheimers 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 Alzheimers 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 Alzheimers 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 patients 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 patients 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
patients 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 Alzheimers Disease Center, Northwestern University Medical School, 320 E.
Superior, Searle 11-467, Chicago, IL 60611 USA,sweintraub@northwestern.edu.
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 patients 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 Alzheimers 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 Alzheimers disease. The ADCQ can be completed using a
paper version or on line atwww.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 Alzheimers 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 Alzheimers
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 mini-
mental 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 Alzheimers 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, OConnor 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 Alzheimers Disease Caregiver Questionnaire
(ADCQ). Tampa, FL, Psychological Assessment Resources., 2002.
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BLESSED DEMENTIA SCALECAREGIVER SCALE
NAME _______________________________________
CHANGES IN PERFORMANCE OF EVERYDAY ACTIVITIES
Inability to perform household tasks ...................... 0 .5 1Inability to cope with small sums money ................ 0 .5 1Inability to remember a short list of items ............... 0 .5 1Inability to find way about indoors ......................... 0 .5 1Inability to find way about familiar street ................. 0 .5 1Inability to interpret surroundings ............................ 0 .5 1(e.g. to recognize whether in hospital or home)Inability to recall recent events ............................... 0 .5 1(e.g. recent outings, relatives visits etc.)Tendency to dwell in the past ................................. 0 .5 1
CHANGES IN HABITSEating: cleanly with proper utensils ....................... 0
messily with spoon only ......................... 1simple solids (no utensils) ....................... 2has to be fed ......................................... 3
Dressing: unaided ................................................ 0occasionally misplaced buttons ............. 1wrong sequence, forgets items .............. 2unable to dress .................................... 3
Sphincter Control: Complete ................................. 0Occasionally wets bed .............. 1Frequently wets bed .................. 2Doubly incontinent .................... 3
CHANGES IN PERSONALITY
Increased rigidity ........................................... 0 1Increased egocentricity ................................. 0 1Impairment of regard for feelings of others .... 0 1Coarsening of affect ................................... 0 1Impairment of emotional control ...................... 0 1
(e.g. increased petulance and irritability)Hilarity in inappropriate situations ................... 0 1Diminished emotional control ........................ 0 1
(e.g. depression)Sexual misdemeanor (de nova in old age) ..... 0 1
CHANGES IN INTEREST AND DRIVES
Hobbies relinquished ....................................... 0 1Diminished initiative or growing apathy ........... 0 1Purposeless hyperactivity ................................ 0 1
LEFT SCORE _________________
BLESSED DEMENTIA SCALEINFORMATION-MEMORY-CONCENTRATION TEST
DATE ________________________ No. ______________
(Ask patient to remember the name & address in the 5-MinuRecall section.)
INFORMATION
Name ......................................................... 0 Age ............................................................. 0 Time (hour) ............................................... 0 Time of day .................................................. 0 Day of Week ................................................. 0 Date ............................................................... 0 Month ............................................................ 0 Season ......................................................... 0 Year ............................................................. 0 Place: Name .............................................. 0
Street .............................................. 0 Town ............................................... 0
Type of Place (e.g. Hospital, home etc.) ....... 0 Recognition of persons .................................. 0 1
PERSONAL MEMORY
Date of Birth ................................................. 0 Place of Birth ................................................ 0 School Attended ............................................ 0 Occupation ................................................... 0 Name of sibling or spouse ............................. 0 Name of any town where patient worked .... 0 Name of employer ....................................... 0
NON-PERSONAL MEMORY
Dates of WWI (1914-1918) ......................... 0 Dates of WWII (1939-1945) ......................... 0 President of the United States ........................ 0 Vice President of the United States ................ 0
5-MINUTE RECALL
(Mr.) J ohn Brown ........................................ 0 1 42 West (Street) ........................................ 0 1 Cambridge, (MA) ......................................... 0 1
CONCENTRATION
Months Backwards .................................... 0 1 Counting 1-20 ................................... 0 1 Counting 20-1 ................................... 0 1
RIGHT SCORE _______________
(Prepared by Dorene M. Rentz, Psy.D. and Andrew EBudson, M.D. after Blessed, Tomlinson & Roth, 1968
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Blessed Dementia Scale (BDS) Administ ration and Scor ing Notes:
There is no agreed upon standard scoring of the BDS. These notes represent our suggestiofor administration and scoring, using information from the original paper and the literaturewhen possible. Note that the number of impaired responses [or errors] are commonlyreported for the BDS, rather than the number of unimpaired [or correct] responses. Thus, 0indicates normal performance or a correct response. The Caregiver Scale is for the clin icianto adminis ter to a caregiver (typically a relative or a nurse). Questions should be askedtactfully. For those items which may be scored 1, .5, or 0, total incompetence in an activ ity
should be given a score of 1, and partial, variable, or intermittent incapacity should be givenscore of .5. The Information-Memory-Concentration test is for the clinician to administer tothe patient. If the patient is asked to memorize the name and address for the 5-MinuteRecall 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 rememberedis repeated until the patient learns it (or up to 5 attempts). For the Information section, thepatient 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 cor rect with in one day, or season that is correct within one week. Recognition of persons is for the persons that thecame with; if they came with two persons there is one possible error for each, and if theycame 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 thpatient for any of the years that these wars took place; a single correct year is suffic ient.(Note that Dates of WWI is an outdated question that is of lit tle value, now typicallyreflecting semantic knowledge that may have been learned in school rather than remote NoPersonal Memory. ) For the Concentration section, score one error for one mistake, andtwo 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 bealtered if necessary to reflect the patients cultural and regional knowledge.
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