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Retrograde amnesia for medical and otherknowledge in a physician with Alzheimer's diseaseWilliam W. Beatty b , Shelley English b & Elliott D. Ross aa Department of Neurology , VAMC Center for Alzheimer's and NeurodegenerativeDiseases University of Oklahoma Health Sciences Center , PO Box 26901, OklahomaCity, OK, 73190, USAb Department of Psychiatry and Behavioral Sciences , University of Oklahoma HealthSciences Center , PO Box 26901, Oklahoma City, OK, 73190, USAPublished online: 17 Jan 2008.

To cite this article: William W. Beatty , Shelley English & Elliott D. Ross (1997) Retrograde amnesia for medical andother knowledge in a physician with Alzheimer's disease, Neurocase: The Neural Basis of Cognition, 3:4, 297-305, DOI:10.1080/13554799708405013

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Neurocase (1997) Vol. 3, pp. 297-305 C Oxford University Press 1997

Retrograde Amnesia for Medical and Other Knowledge in a Physician with Alzheimer’s Disease

William W. Beatty, Shelley English and Elliott D. Ross’ Department of Psychiatry and Behavioral Sciences and ‘Department of Neurology and VAMC Center for Alzheimer’s and Neurodegenerative Diseases, University of Oklahoma Health Sciences Center, PO Box 26901, Oklahoma City, OK 731 90, USA

Abstract

Previous studies of patients with Alzheimer’s disease (AD) demonstrate that these patients exhibit marked loss of premorbldly acquired knowledge with a tendency for relative preservation of information from the distant past. Few studies have examined the multiple components of remote memory in the same patients and no study has measured memory for old (1.e. obsolete) and recent aspects of any patient’s professional knowledge. We studied two retired physicians: an internist (A) with probable AD, and a general practitioner (P) with Parkinson’s disease. Both were symptomatic for about 5 years. A displayed marked and general deficits in remote memory, and on almost all tests showed relatively better memory for more recent information. P performed normally on all remote memory tests. In AD, memory for premorbid knowledge appears to deteriorate rapidly over the course of the disease; more recent memories may be partially protected because they are more often rehearsed.

Introduction

A common observation during interviews or conversations with patients with Alzheimer’s disease (AD) is that they appear to possess almost no memory for events in the recent past, but they sometimes can relate very detailed stories about events that occurred in the distant past. The fact that these stories are highly consistent in content from one retelling to another lends credence to the inference that these recollections are genuine memories of events that actually occurred, rather than mere confabulations.

Attempts to confirm these clinical impressions by more systematic study have led to mixed results. There is general agreement that AD patients exhibit marked and general impairment in recall of remote memories throughout their lives (Beatty et al., 1988; Sagar et al., 1988; Wilson et al., 1981) and clear but usually less severe impairments in recognition of information from the recent and distant past (Kopelman, 1989). Controversy exists, however, about whether the deficit in recall is temporally graded, with knowledge from the distant past being relatively spared.

The existence of temporally graded retrograde amnesia (RA) in AD has been reported for a variety of knowledge domains including identification of famous persons from

photographs (Beatty et af. , 1988), recall of well known public events from news stories (Sagar et al., 1988; Kopelman, 1989), and knowledge of the geography of regions of current and former residences (Beatty and Salmon, 1991). There are also failures to observe temporally graded RA (Wilson et al., 1981; Dall’Ora et al., 1989), and, when asked to generate memories of incidents in response to standard word cues, AD patients, like normal elderly controls, recall most of their memories from the recent as opposed to the distant past (Sagar et al., 1988, 1991).

Several factors may contribute to the uncertainty about the existence of temporally graded RA in AD. First, the effect, if it exists, is certainly small in magnitude. Second, tests like Public Events and Famous Faces may be inherently biased to yield temporally graded RA for memory-impaired subjects because items from distant time periods tap information from semantic memory while items from more recent time periods concern information that is still in episodic memory (Cermak, 1984). Finally, on tests of public information there is no way of determining whether a failed item was ever known.

Correspondence to: William W. Beatty, Ph.D., Department of Psychiatry and Behavioral Sciences, University of Oklahoma Health Sciences Center, Suite 410, Rogers Building, PO Box 26901, Oklahoma City, OK 73190, USA. Tel: (405) 271-2474; Fax: (405) 271-6236; e-mail: wbeatty @rex.uokhsc.edu

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298 W. W. Beatty, S. English and E. D. Ross

This latter difficulty does not apply to research with Kopelman’s ( 1989) autobiographical memory test, but on that instrument all of the information from the ‘Recent Life’ period is drawn from the 5-year period immediately prior to testing. Because especially poor performance on this time period entirely accounts for the temporal gradient of RA displayed by AD patients, it is likely that deficits in remembering information that occurred after the onset of dementia (i.e. anterograde memory impairments) contrib- ute significantly to the observed pattern of results.

For the reasons described above, it is clear that an investigation of temporal gradients of remote memory in AD must include some tests that draw items exclusively from premorbid semantic memory. Tulving (1972) stated that knowledge about one’s own profession is a form of semantic knowledge. Butters and Cermak ( 1986) demon- strated that PZ, a well known experimental psychologist who developed alcoholic Korsakoff’ s syndrome (AKS), showed relative preservation of ‘old’ professional know- ledge, a pattern that paralleled his performance on conven- tional remote memory tests such as Famous Faces. This finding suggested that temporally graded RA for purely semantic knowledge can occur in AKS.

Medical knowledge also changes rapidly and we exploited this situation to create a test containing older and more recent items appropriate for physicians in general practice, family practice or internal medicine. Following the logic of the earlier study of PZ (Butters and Cermak, 1986). the test of medical knowledge was designed to sample only information from semantic memory from different time periods. Even if this untestable assumption was met, we could not be certain that the physician- subjects had ever known the answers to items that they failed. Consequently, we also included two novel tests of personal semantic memory that tapped information about the vehicles that patients had once owned and their former residences.

In the present paper, we report findings on several measures of remote memory from two physicians, one an internist diagnosed with AD, the other a general practi- tioner with Parkinson’s disease (PD). Previous research on remote memory in PD has generally found that patients without dementia exhibit no impairment, while PD patients with dementia exhibit mild deficits of comparable degree across all past time periods (Freedman et al., 1984; Huber rt (11.. 1986; but see Sagar et al., 1988).

Case descriptors Dr P is a right-handed Caucasian male who practised medicine in a small town for 48 years until he retired at age 74. About 1 year later, a neurological examination revealed cogwheel rigidity of the neck and limbs on the left side, bradykinesia, shortened stride, absence of left arm swing while walking, mild tremor at rest, and some disturbance of balance. Treatment with Sinemet resulted in

marked improvement of all symptoms within 2 months. supporting the diagnosis of idiopathic PD.

At the time of testing, P was 80 years old, living independently, and although he was receiving Sinemet (80 mg/day I-dopa) and Parlodel (3 .375 mg/day), h i x condition had deteriorated to Stage I11 on the Hoehn and Yahr ( 1967) scale. A neuropsychological evaluation to determine competence to live alone demonstrated a WAIS- R (Wechsler, 1981) VIQ of 123 (well above average) and age-scaled scores of 8 and 9 (low average) respectively on the Picture Completion and Picture Arrangement subtests. When given additional time to respond, his performance improved to 9 and 12 (age-scaled scores) respectively on the above subtests. Because of his marked slowness and clumsiness of hand and upper extremity movenienl, the other performance tests from the WAIS-R were not administered.

On the WMS-R (Wechsler, 1987), Dr P attained scores of 93 (average) on both the General Memory and Delayed Recall Indices.

Dr A is a right-handed Caucasian male who practised medicine for 45 years (mostly in an urban area) until his retirement at age 71. He served as a Clinical Professor o f Medicine at an area medical school and was elected as ;I

Fellow of the American College of Physicians at age 52. About 5 years before the present tests his wife and the

chief nurse in his private practice noticed increasingly poor memory and a tendency to confuse one patient with another. Comprehensive medical and neurological evalua- tion confirmed a dementia syndrome. A series of CT and MRI scans over a 2-year period revealed progressivc ventricular enlargement and mild cortical atrophy without masses, ischemic changes or other focal signs. He met criteria (McKhann et al., 1984) for probable AD and retired from his medical practice.

Comprehensive neuropsychological evaluation 1 year before the present tests revealed a VIQ of 92, PIQ of 90, and FSIQ of 89 on the WAIS-R (Wechsler, 1981). His premorbid VIQ, estimated using the AMNART (Grober and Sliwinski, 199 1 ), was 124, indicating marked loss from premorbid functioning. On the WMS-R (Wechsler, 1987) he scored 58 on the General Memory Index and 56 on the Delayed Recall Index (severely impaired). Problem solving and naming were also impaired.

Subsequent memory testing with the Hopkins Verbal Learning Test (Brandt, 199 I ), a 12-word categorized list, revealed unaided free recall scores of two, three. and four correct words on the three-learning trials and a score ot one word after a 10-min delay. Dr A made no intrusions on these free recall trials. With semantic cues at a 30-niin delay he recalled one word and made three intrusions. Immediately afterwards, A was read a list of 24 words: 12 from the list, six semantically related distractors, and six unrelated distractors. On yesho recognition his scores were: true positives (i.e. hits), 1 I ; false negatives (i.e. misses), 1; false positives (i.e. false alarms). 9; overall

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accuracy, 58% correct. All of these scores indicate severe memory impairment.

On a test of visual memory for four items, A copied the circle, diamond and cross accurately but he was unable to copy the cube, despite several attempts. Thirty minutes later he recalled none of the stimuli.

At the time of the present tests, Dr A was 75 years old and residing in a nursing home; he was receiving Haldol (1 mg tid), Paxil (20 mg/day), trazodone (50 mg/day), and KCI (10 mg every other day).

Dr P, and Dr A’s wife and each of the control subjects gave written informed consent after a thorough explanation of the procedures which were approved by the local Institutional Review Board in conformation to the Helsinki Declaration.

Procedure

At the time of the remote survey study, P and A also received the following tests: Mini-Mental State Exam (MMSE. Folstein et d., 1975); the oral version of the Symbol Digit Modalities Test (SDMT; Smith, 1982); Forward Digit Span from the WAIS-R (Wechsler, 1981); Forward Visual Memory Span from the WMS-R (Wechsler, 1987); the Boston Naming Test (BNT; Kaplan et al., 1983); the Benton Line Orientation Test (Benton et al., 1983); a letter fluency test on which the subjects were allowed 60 s each to generate as many words as possible that began with the letters f, a, and s; the Animals Category Fluency Test on which they were allowed 60 s to generate the names of as many animals as possible; a shortened (64-card) version of the Wisconsin Card Sorting Test (WCST; Heaton, 198 1 ), a measure of problem solving; and the Sequences Test (Beatty and Monson, 1990), which requires arranging line drawings in correct order to ‘make a sensible story’. Unlike the Picture Arrangement subtest from the WAIS-R (Wechsler, 1981), the Sequences Test is not timed. uses much larger pictures, and employs highly familiar themes which are not subject to alternative inter- pretations. The 30-item Sequences Test is designed to minimize confounding of sequencing ability with mild losses of visual acuity, mild visuomotor disturbances, motor and cognitive slowing and susceptibility to percep- tual confusion, conditions that are commonly observed in patients with PD, AD or other neurological disorders that can complicate interpretation of scores on the Picture Arrangement test.

P and A received the following tests of remote memory.

Famous Faces Test Subjects were shown black and white photographs of people who were known during the 1940s 1950s 1960s, 1970s and 1980s, and asked to name the person shown in the photograph. There were 15 items from each decade. The stimuli were identical to those used in our earlier study

(Beatty et al., 1988) which demonstrated a weak temporal gradient of RA for the AD patients. In the present study, for items that could not be correctly recalled, subjects were shown a card containing four names (the correct name and three plausible distractors) and asked to guess the name of the person shown in the photograph.

Presidents Test P and A were asked to name the current president of the US, the president before him and so on until they named eight former presidents. If any errors occurred, they were shown cards containing the names of the eight most recent presidents and asked to arrange them in reverse order, starting with the current president.

Test of Medical Knowledge This test was created to tap practical knowledge related to the diagnosis and treatment of conditions and diseases of the sorts regularly encountered by general practitioners and internists in private practice. Items were selected from the 1940, 1950, 1961, and 1977 editions of the Merck Manual (Merck and Company, 1940; 1950; 1961; 1977), and from the 1980 edition of Goodman and Gilman’s textbook of pharmacology (Gilman et al., 1980). Because both AD and PD had insidious onsets, and overt symptoms may not be evident for many years after physical and mental functions began to decline, we made no attempt to sample up-to-date information of the sort contained in medical journals.

The Test of Medical Knowledge contained three types of items: ‘old’ knowledge (25 points) concerned treatments and procedures that were once ‘state-of-the-art’ but were obsolete by 1961; ‘new’ knowledge (31 points) concerned treatments and procedures that were developed after 196 I ; and ‘general’ knowledge (78 points) concerned treatments and procedures that were accepted through the time periods spanned by the careers of Drs P and A.

Geographical Knowledge Subjects were shown an outline map of Oklahoma and portions of the surrounding states. On the map were printed 33 numbered dots. Subjects were shown a list of 20 cities (11 from Oklahoma, nine from surrounding states) and asked to indicate (by number) which dot corresponded to the location of each city.

Autobiographical Tests The Autobiographical Memory Interview (AMI; Kopelman et ul., 1990) was administered and scored according to procedures described in the test manual. Only Dr A received this test.

Both P and A were asked to draw floor plans of all of the homes they had ever lived in and describe all of the automobiles they had owned throughout their lives (the

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Table 1. Cognitive performance by the two physicians: raw score (percentile)

A P

MMSE Oral SDMT Forward Digit Span Forward Visual Memory Span BNT, no cues Letter Fluency Animals Line Orientation WCST-64 cards

Categories Perseverative Responses

Sequences

28 38 (26)

8 (36) 7 (10)

47 (25) 44 (82) 17 (29) 29 (98)

0 31 26 (12)

Percentiles are based on the following sources: Lezak (1995) for the Oral SDMT; Ivnik et al. (1996) for BNT, Letter Fluency and Line Orientation; Beatty and Monson (1990) for sequences; local controls for the forward memory spans and Animals. Normative data are not available for the 64-card version of the WCST.

'Cars' test). These reports, as well as data from interviews about autobiographical information, were checked for accuracy by contacting close relatives. The 'Cars' test has not been used previously to study RA, but in an earlier study (Beatty et al., 1987), the temporal lobe amnesic patient, MRL, drew accurate floor plans of his former residences from the distant past, but had only fuzzy recollections of homes he had lived in during the 15 years preceding his amnestic episode. His temporally graded RA for visuospatial information assessed in this way was similar in form and extent to the memory gradients deter- mined using the Famous Faces and Public Events tests.

Results Table 1 summarizes performances by the two physicians on several measures of cognitive performance obtained at the time of remote memory testing. Both patients exhibited some slowing of information processing speed (oral SDMT), and this effect was greater for A. Both physicians performed within normal limits on forward digit span, a measure of attention and immediate memory for verbal

Table 2. Percentage correct on the Famous Faces Test

information, but both were somewhat impaired on forward visual memory span, a measure of attention and immediate memory for non-verbal information.

Dr A performed normally on the BNT, a measure of confrontation naming that is often deficient in AD, while Dr P scored in the low end of the normal range. This pattern was reversed on the letter fluency task on which P performed well and A was mildly impaired. Both physicians scored below average on the Animals Test, a measure of category fluency; the deficit was greater for A.

Both doctors attained very high scores on the Line Orientation test, a measure of visuospatial perception, but they performed poorly on the WCST, which measures concept formation and set shifting. On the Sequences Test, P was moderately impaired while A was more severely impaired.

Table 2 summarizes performance on the Famous Faces Test for P, A and a group of 1 1 male normal control subjects who were also retired physicians. The controls averaged 74.6 (range: 69-81) years of age. In terms of overall performance on the recall portion of the task, A named significantly fewer famous people than did the controls. His impairment was also statistically significant for the 1940s and the 1970s, but not for the other decades. All of the photographs A was able to name correctly were from the 1940s, 1950s and 1960s; he could not recall the names of any of the 30 persons drawn from the 1970s and 1980s. P showed normal recall for the 1940s and 1950% below average recall for the 1960s and 197Os, and poor performance for the 1980s. Finally, the normal controls exhibited comparable accuracy for identifying photographs from the 1940s, 1950s, 1960s and 1970s, and somewhat poorer performance for the items from the 1980s. Although A appears to exhibit temporally graded RA, the lower performances of P and the controls for items from the 1980s complicate this interpretation.

Results from the recognition portion of the Famous Faces Test conflict with the pattern on recall. Here it can be seen that both P and A performed well within the range of controls overall and for each decade, and both patients exhibited roughly comparable performances across the five decades. In contrast to expectation, A attained his

1940s 1950s 1960s 1970s 1980s Overall

Recull

Dr P 47 53 33 27 7 27 Dr A I 3h 33 13 Oh 0 9 h

Recognition Controls" 83 (67-100) 85 (60-100) 88 (73-100) 93 (60- 100) 90 (47-100) 88 (64-96) Dr P 93 93 87 100 93 93 Dr A 73 87 73 73 93 80

Controlsu 45 (27-73) 55 (27-73) 41 (13-73) 48 (7-80) 32 (7-73) 44 (17-64)

'Mean (range) of performances. hPerformance more than 2 SD below controls.

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best recognition memory performance for items from the 1980s.

On the Presidents Test, P correctly recited the names of all eight recent presidents in reverse order. (Actually he recited 14 correctly until stopped by the examiner.) A could not recall any of the recent presidents spontaneously or when given semantic cues. When given the first name and first letter of the last name of the president, he correctly named Clinton and Reagan, but could not name Bush or Carter. A was then shown a set of eight index cards with the name of the president printed on each card. When asked to arrange the names in reverse order starting with the current president, he correctly selected Clinton; his arrangement of the remaining seven presidents was essentially random (i.e. Kennedy, Carter, Johnson, Bush, Reagan, Nixon, Ford).

Findings for the Test of Medical Knowledge are shown in Table 3. Two control groups of physicians were recruited for comparison with P and A. The retired control doctors (n = 9) were internists or general practitioners who had retired from active medical practice 1 - 10 years before testing. They averaged 76.9 (range: 69-82) years of age. The young family practitioners (n = 5) were actively practising in a single group practice. They had completed their residences 1 - 1 1 years before testing.

A two-group (young versus old doctors) x age of items ANOVA revealed a significant main effect of Item Age (F (1,12) = 78.68, P < 0.001) and a significant interaction of group x item age (F (1,12) = 47.17, P < 0.001). The main effect of group was not significant (F < 1). Sub- sequent analyses of the interaction revealed that the retired doctors attained significantly higher scores on the old items (F (1,12) = 27.33, P < 0.001), but the young doctors performed better on the new items (F (1,12) = 16.51, P < 0.002). On the general items, the young doctors also attained higher scores (F (1,12) = 8.57, P < 0.02).

Dr P's scores on all types of items were almost identical to the average performance by the retired control doctors. By contrast, Dr A performed more poorly than the other retired physicians, regardless of the age of the items. However, significant differences in performance were observed only for old and general items, on which A's performance was 25 or 26% below that of the retired control doctors, but not for the new items for which the difference was 19%.

Geographical knowledge, which can be considered to be a test of visuospatial semantic knowledge, was studied by having P and A attempt to locate cities on an outline map of their home region. A performed poorly, correctly locating only seven of 20 cities. His score (35%) was significantly below the average of 86.5% attained by age-matched controls (Z = 4.68, P < 0.001). By contrast, P correctly located 100% of the cities. Because both A and P had lived their entire lives in a single region it was not possible to examine temporal gradients for visuospatial information using geographical knowledge as the test domain.

Instead, both physicians were asked to draw floor plans of all of the homes they had lived in throughout their lives, state the address of each home, and provide the dates they had resided in these homes. These drawings were then shown to family members for verification. P remembered every home in which he had lived, its address, and accurately dated his times of residence. Within the limits of his relatives' knowledge, his floor plans were accurate. By contrast, A could only recall information about his most recent residence. He correctly stated the address and years of residence, but omitted two major features from his floor plan (kitchen, master bedroom). When asked about previous residences, he could only describe vaguely a generic three-bedroom ranch house and he was unable to state in which city this house was located.

Table 4 shows data for A and three normal elderly controls on the Autobiographical Memory Interview (AMI). The controls averaged 76.3 (range: 68-81) years of age. The controls performed very well on both the autobiographical incident schedule and on the personal semantic schedule. Their performances were uniformly excellent across the three time periods measured. By contrast, A recalled very little personal semantic know- ledge and few autobiographical incidents from any period in his life. Surprisingly, his performance was best for the most recent period (spanning approximately the most recent 5 years). Because five different instances of

Table 3. Percentage correct on the Test of Medical Knowledge

Old items New items General items

Retired control 57 (48-66) 61 (48-79) 82 (76-94) doctors'

Practitioners' Young family 34 (20-48) 84 (79-87) 93 (89-99)

Dr P 52 61 80 Dr A 32' 42 56'

'Mean (range) of performances. bSignificantly different ( P < 0.05) from retired control doctors. 'Performance more than 2 SD below retired control doctors.

Table 4. Percentage correct on the Autobiographical Memory Interview

Childhood Early adulthood Recent life

Semantic Controls' 87 (91) 90 (94) 96 (100) Dr Ab 10 (19) 17 36

Controls' 95 (loo) 95 (loo) 95 (loo) Autobiographical incidents

Dr Ab 5 0 (10) 24

'Values are means. Numbers in parentheses are the mean percentage correct if memories that could not be verified but were not obvious confabulations are considered correct. bValues reported are for memories that could be verified. Values in parentheses are percentage correct if memories that could not be verified but were not obvious confabulations are scored as correct.

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302 W. W. Beatty, S. English and E. D. Ross

confabulation (i.e. items on which his answers were clearly false or impossible) were noted in A’s interview, it is probably prudent to discount the autobiographical informa- tion he supplied which could not be confirmed or dis- confirmed by relatives. In fact, it makes little difference in the overall pattern of the results if these items are scored as correct or incorrect. Based on reports of relatives, no instances of confabulation were noted for controls and it is likely that their unconfirmed memories were for real events of which their relatives simply had no knowledge.

We did not have access to the AM1 at the time P was tested. However, he was asked to recall major events throughout his life (e.g. weddings, births of children, major vacation trips, details of his professional life), and to date these events. Within the limits of his relatives’ knowledge he performed accurately with respect to the facts about the events described and the dates of occurrence. No instances of patently false memories were noted in P’s descriptions.

As a final inquiry into the status of remote memory in P and A, they were asked to describe the automobile they currently or most recently owned (i.e. year, make, style, color) and work backwards in time describing each car they had previously owned. They were also asked explicitly to describe the first car they had owned. Within the limits of his relatives’ knowledge, P was able to state accurately the year and make of every car he or his late wife had ever owned. He was not always certain about the style or color and he mentioned owning two cars that his relatives could not recall, although they were not certain that he had not owned these vehicles. A, by contrast, correctly described the year, style, make and color of his current auto and the year and make of this wife’s current car, but he could not remember any vehicles he had owned previously. When asked to describe his first car, A again described his current auto. almost verbatim.

Discussion On each of the seven remote memory tests, Dr A exhibited clear deficits, regardless of whether the knowledge tapped was episodic, semantic, personal-autobiographical, generic, or highly specialized. These findings are consistent with the results of studies reviewed earlier that demonstrate marked deficits in remote memory in AD which span patients’ lifetimes.

In contrast to the results of some previous studies (Beatty et al., 1988; Sagar et al., 1988; Kopelman, 1989; Beatty and Salmon, 1991). Dr A did not exhibit temporally graded RA on most tests. Instead he showed slightly better performance for information from more recent time periods. This pattern was observed on the Presidents Test, the Test of Medical Knowledge, the recognition portion of the Famous Faces Test, on the AM1 and on tests of knowledge of former residences and cars he had owned throughout his life. Dr A did show a mild temporal gradient of RA on the recall portion of the Famous Faces Test, but

interpretation of this result is uncertain because Dr P and the normal controls showed similar patterns of relatively poorer performance for the more recent decades. Cermak (1984) has suggested that the distribution of items from episodic and semantic memory of the Famous Faces Test may not be constant across time periods, potentially resulting in artifactual temporal gradients.

Dr A’s ‘reverse temporal gradient of RA’ was especially evident on both the personal semantic and autobiographicnl incident schedules from the AMI, on which he recalled substantially more information from his recent life than from earlier periods.

This result is in direct contradiction to findings of Kopelman (1989) who developed the AMI, but possibly consistent with findings (Sagar et al., 1988; 199 I ) that AD patients recall most of their memories to standard word cues from the recent past under test conditions that do not constrain responses to particular time periods. Examination of the data reported by Kopelman for his AD patients (1989, Figs 7 and 8, p. 450) indicates that these patients averaged -69% correct for semantic memories from childhood and early adulthood compared to 52% for recent life. For the autobiographical incident schedule, Kopel- man’s patients averaged 61, 55 and 39% correct for childhood, early adulthood and recent life periods respect- ively.

Comparison of these data with those from Table 4 indicates that A recalled only slightly less information from his recent life than did Kopelman’s patients, but his recall of information about his childhood and early adult life was substantially more impaired. As a result, the mild temporal gradient of RA observed by Kopelman became a reverse temporal gradient for Dr A.

Kopelman (1989, p. 439) reported that the mean duration of symptoms for his patients was 2.9 years, while Dr A had exhibited memory problems for at least 5 years. This suggests the following explanation for the present results. Very early in the course of AD remote memories are, in fact, better preserved than recent (i.e. anterograde) memories, a phenomenon that virtually every clinician and caregiver has observed. As the disease progresses, access to remote memories (and possibly their representations as well) deteriorates. This process probably affects all memories more or less equally (at least in terms of their biological substrates), but ‘recent’ memories are ostensibly less affected because contemporary experiences (e.g. driving or riding in the patient’s current car) or reminders from relatives (e.g. ‘You remember last Christmas’) provide more opportunities to rehearse recent memories than memories from the more distant past. Dr A’s wife visited him almost every day, providing ample opportu- nities for rehearsal of recent experiences. However, equally advanced AD patients who were socially isolated from their families might be expected to recall very little autobiographical information from any temporal period i n their lives.

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Remote memory in Alzheimer’s disease 303

The idea that rehearsal might improve memories from the past in a mildly demented AD patient is based on the hypothesis that impaired access is a major source of semantic memory loss, at least early in the course of the disease. The source of the semantic memory deficit in AD remains controversial. Some have argued that the structural representations of knowledge are irreversibly degraded (e.g. Hodges et al., 1992; Martin, 1992), but others main- tain that the representations are intact, but the knowledge is inaccessible (e.g. Nebes, 1992; Ober et al., 1995).

To examine the plausibility of the rehearsal idea we attempted to provide reminders about personal semantic knowledge from the early adult period of A’s life. During the course of other testing we engaged him in conversation about his first wedding, his children and his first pro- fessional experiences. We tried to act as much like relatives as possible, correcting his errors, but not actually drilling him. About 24 hours after the last of four such sessions, the Personal Semantic Schedule of the AM1 (Kopelman et al., 1990) was readministered. A scored 19, 52, and 33% correct for the childhood, early adult and recent life periods for verified memories. Compared with the results shown in Table 4, A exhibited relatively selective improvement for the early adult period, which is consistent with the rehearsal idea elaborated above. Because A performed very poorly on a verbal learning test with a much shorter (i.e. 30 min) delay, it seems likely that our ‘rehearsal treatment’ mainly stimulated access to autobiographical knowledge that was partly intact, but other interpretations are clearly possible.

A prospective study in which remote memory in AD patients was studied longitudinally, ideally from the earliest sign of memory decline, will be required to test this hypothesis rigorously. Such a study would have to extend over several years because Greene and Hodges ( 1996) recently reported that AD patients showed no loss in autobiographical memory over a 1 -year interval, although they did exhibit significant declines in knowledge of famous people.

The model proposed above is consistent with the known progression of neuropathological changes in the temporal lobe in AD. Early in the disease course, pathology appears to affect primarily the amygdala and the hippocampal formation including the hippocampus proper and the entorhinal cortex (Hof and Morrison, 1994). As the disease progresses, neocortical areas, especially in the temporal lobes, become more involved.

Studies of patients with temporal lobe lesions caused by hypoxia, ischemia or encephalitis reveal a close correlation between the size and location of the lesion and the extent of anterograde and retrograde memory loss. Thus, patient RB who sustained only bilateral loss of the entire CAI field of the hippocampus (Zola-Morgan et af., 1986) showed only anterograde amnesia, while other patients with nearly total destruction of the hippocampus (Beatty et al., 1987; Squire et af., 1989) showed sharply temporally graded RA as

well. More extensive bilateral damage to the medial and lateral temporal lobes caused by herpes encephalitis was associated with dense anterograde amnesia and extensive RA which spanned the patient’s lifespan and was not temporally graded (Cermak and O’Brien, 1983). Finally, in patients with semantic dementia in which the temporal neocortex is severely damaged but the hippocampus is relatively spared (Harasty et al., 1996), remote memories are severely disturbed, but recent personal memory is better preserved (Graham and Hodges, 1997).

Kopelman ( 199 1 ) has reported that the extent of remote memory impairment in AD is correlated with the severity of impairment on tests of frontal lobe function ( e g card sorting, letter fluency). Our data for Drs P and A suggest that card sorting may not be a particularly important predictor although letter fluency might be.

Dr A’s poor performance on the Sequences Test mirrored his difficulty sequencing US presidents. Further, his intrusion on the ‘Cars’ test and some of his confabulations on the AM1 suggest an inability to maintain the temporal order of events in memory. Yet Kopelman reported no significant correlation of WAIS Picture Arrangement error scores with any of the remote memory tests.

The Picture Arrangement Test is very difficult for the normal elderly (Wechsler, 1981; Ivnik et al., 1992) and it is possible that the low correlations of this test with perform- ances on remote memory tests reflect restricted range of performance on the Picture Arrangement Test by the AD patients. An easier test such as the Sequences Test (Beatty and Monson, 1990) might be a better choice for future research.

During testing Dr A was receiving three different psychoactive medications, which complicates interpreta- tion of his test results. Memory is known to be vulnerable to drugs, especially agents with anticholinergic or sedative properties. The various aspects of memory, however, are not equally affected; acquisition and recall of new informa- tion are usually most vulnerable (Duka et al., 1996). For example, the anticholinergic scopolamine profoundly dis- rupted anterograde verbal and visuospatial memory, but did not affect remote memory in normal controls (Troster et af., 1989). The Famous Faces and geographical knowledge tests used in the scopolamine study were identical to those used in the present study. Because the drug effect was opposite to the pattern of memory loss observed for Dr A (i.e. more recent memory was affected by scopolamine) it does not seem likely that Dr A’s medicatiohs produced the temporal pattern of RA that he displayed.

In most respects, the performance of Dr P on the various remote memory tests is typical of what would be expected of a non-demented PD patient of above-average premorbid intellectual ability (Freedman et al., 1984; Huber et al., 1986). His mild difficulty in recalling the names of famous people on the Famous Faces Test probably reflects his below-average performance in confrontation naming (i.e. the BNT). This interpretation is supported by P’s

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304 W. W. Beatty, S. English and E. D. Ross

excellent score on the recognition portion of the Famous Faces Test.

On the Test of Medical Knowledge, P scored almost exactly at the average of the nine retired physicians on each of the three sections of the test, indicating that knowledge of his profession was both intact and accessible. On the other tests of public information and personal remote memory (i.e. Presidents, Geographical Knowledge, Floor Plans and Cars), P displayed accurate knowledge of the various items and the ability to arrange the items in correct temporal order.

Sagar and colleagues (Sagar et al., 1988; Sullivan et al., 1989) have shown that sequencing ability, including the ability to order information in memory, is impaired in PD, even among patients of normal mental status. P’s below- average performance on the Sequence Test used in the present study is typical of other PD patients we have studied (Beatty and Monson, 1990). Yet Dr P was able to sequence US presidents, as well as his own previous residences and automobiles, with considerable precision. Perhaps his retained ability can be attributed to his lifelong interest in history. Dr P had traveled extensively, both in the US and abroad, traced his family genealogy back several hundred years to its origin in what is now modem Norway, and served for more than 20 years as volunteer Director-Curator of the small historical museum in the rural county in which he lived.

Acknowledgements Supported by Grant HR4-087 from the Oklahoma Center for the Advancement of Science and Technology.

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Received on 13 November, 1996; resubmitted on I0 February, 1997; accepted on 15 February, 1997

Retrograde amnesia for medical and other knowledge in a physician with Alzheimer’s disease

W. W. Beatty, S. English and E. D. Ross Abstract : Previous studies of patients with Alzheimer’s disease (AD) demonstrate that these patients exhibit marked loss of premorbidly acquired know- ledge with a tendency for relative preservation of information from the distant past. Few studies have examined the multiple components of remote memory in the same patients and no study has measured memory for old (i.e. obsolete) and recent aspects of any patient’s professional knowledge. We studied two retired physicians: an internist (A) with probable AD, and a general practitioner (P) with Parkinson’s disease. Both were symptomatic for about 5 years. A displayed marked and general deficits in remote memory, and on almost all tests showed relatively better memory for more recent information. P performed normally on all remote memory tests. In AD, memory for premorbid knowledge appears to deteriorate rapidly over the course of the disease; more recent memories may be partially protected because they are more often rehearsed.

Journal Neurocase 1997; 3: 297-305

Neurocase Reference Number

Primary diagnosis of interest Alzheimer’s disease

Author’s designation of cases (Dr) A (Dr) P

Key theoretical issue 0 Temporal gradient of retrograde amnesia

Key words: Alzheimer’s disease; retrograde amnesia; remote memory; autobiographical memory

085

Scan, EEG and related measures

Standardized assessment CT, MRI scans of head

WAIS-R, WMS-R, MMSE, BNT, LOT, Verbal Fluency, WCST, Famous Faces Test, President’s Test, Neurological exam, Autobiographical Memory Interview

Other assessment Test of Medical Knowledge, Geographical Knowledge, Knowledge of former residences and cars owned

Lesion location 0 Diffuse atrophy

Lesion type Not known

Language English

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