Neurobiology of Aging, Vol. 11, pp. 253-357. © Pergamon Press plc, 1990. Printed in the U.S.A. 0197-4580/90 $3.00 + .00

ABSTRACTS

CLINICAL COURSE

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THE CLINICAL COURSE OF ALZNEIMER'S DISEASE. *B. Relsberg, E. Franssen, A. Kluger, S. Sclan, E. Shulman, G. Steinberg, M. J. de Leon, and S. H. Ferrls. Aging and Dementia Research Center, New York University Medical Center, New York, New York, 10016 USA.

Accurate description of the clinical course of Alzhelmer's disease ( . ~ ) requires: (i) study of the earliest symptoms; (2) measures capable of detailing the entire course of/d), including the final stages when patients are said to be untestable; and (3) detailed cross sectional observation and longitudinal follow-up. Our current estimates of the typical time course of ADbased upon empirical cross-sectional data are as follows:

WPI£g TIM c ~ U | OF l ~ l l R | l ' $ I l e a l (~|)

I . . . . , i, ,i,i . L

min i m == m!!'

Our cross-sectional results suggest that: (i) the early temporal course of AD cannot be reliably distinguished from normal individuals solely on the basis of mental status and psychometric measures, and (2) psychometric and mental status measures invariably bottom out by the beginning of the final third of the temporal course of AD. More information is needed regarding the diagnosis of AD during the incipient, questionable third of the prospectively identifiable time course, and the precursors of#J) in ostensibly normal persons with AAMI (GDS stage 2) need to be identified. We also conducted a longitudinal study of the course of normal aging and progressive AD'. From 1978 to 1982 we identified 144 subjects with normal aging and probable AD. These subjects were followed-up after a mean interval of 3h yeats and again after a mean of 9 years. Follow-ups included residential and nursing home visits, where necessary. Our longitudinal results provide improved information regarding the reliability of the diagnosis of incipient dementia and the time course of the disease process.

~SDHHS grant AG03051 from the National Institute on Aging.

2 THE COURSE OF ALZHEIMER'S DISEASE AS RELATED TO CSF BIOCHEMISTRY, NEUROLOGICAL STATUS AND COGNITIVE FUNCTION. "R Adolfsson, R Ekman, L Forsgren, T Kadsson, P Westar, E Widedov Umea Institute for Basic Research in Memory, Department of Psychiatry, University of Umea, S-901 Umea, Sweden

The objective of this longitudinal study of 50-75 patients with Alzhelmer's disease was to study the natural course of the disease by means of ordinary clinical investigation tools, focusing on memory and higher cortical functions, neurological signs, behavioral symptoms, adl capacity and CSF biochemistry In addition all patients were repeatedly Investigated by CT scan and EEG Special emphasis was put on studying the peripheral glucose metabolism Preliminary results is presented in this abstract Major clinical findings: - The progress of the disease is variacle in terms of "speed", associated neurological and psychic symptoms. - Early in the disease neurological dysfunction is evident by upper extremity dysrythmia and dyscoordination. - The progression of apraxla follows a hierarchical pattern, from eady signs of difficulties with mental representation of complex movements, followed by loss of imitative ability, handling of real objects and finally loss of body awareness. - The decline of cognitive abilities, from the initial evaluation, is most marked in non- memory functions. - Behavior disturbances and psychiatric symptoms are relatively late signs. Major biochemical findings: -CSF somatostatin (SRIF), delta-sleep-inducing paptide (DSIP), and acetyicholine esterase is significantly lower compared to age-matched control, and remain thereafter, dudng the progression of the disease, unchanged.

- No significant conel~ions were ~und between clinical variacles and SCF biochemi~ry, with the exception of the actMty of acetylchclina esterase and the level of HVA. The enzyme activity was co.clued to global impairment, adl capacity and apraxia/aphasia. The HVA concentration ~ the finding of asymm~ric m~or impairment. - CSF SRIF is sign~icantly correl~ed with the glucose raise ~rea under the cuwe), following an oral glucose load. Conclueionl Throe are no sim~e corr.=ions between CSF ~ochemi=ry and clinical findings, including memory functions. Two findings, hitherto not reposed, was disclosed. Firstly. the sign~cant reduction of CSF DSIP and secondly the intimate rel=ion between CSF SRIF and peripheral ~ucose homeostasis. These findings mig~ have pathogen~ic as well as therape~ic im~ications.

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LEUKO-ARAIOSIS AND PROGNOSIS IN DEMENTIA. *Vladimir Hachinski and Harold Merskey on behalf of the University of Western Ontario Dementia Study. Department of Clinical Neurological Sciences, The University of Western Ontario, London, Ontario, Canada.

In a case control study of 140 demented patients and ii0 controls we evaluated the significance of white matter changes (leuko-araiosis) on computerized tomography of the brain in relation to the severity and progression of the dementia.

We found that patients with leuko-araiosis had more severe dementia than patients without (Extended Scale of Dementia of 138 ~ 41 compared to 178 ± 39 p < 0.001 - normal value 250) and there was a trend for patients with leuko-araiosis to have more rapid progression of their illness. In a related clinico-pathological study we found that patients with leuko-araiosis had an earlier mortality than those without (Janota et al, Arch Neurol 46: 1124-1128, 1989).

Leuko-araiosis is associated with a more severe degree of dementia and an earlier mortality among demented patients. It remains uncertain whether leuko-araiosis represents a marker or a contributing cause of deterioration.

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NEUROPSYCHOLOGICAL VALIDATION OF TWO DEMENTIA CATEGORIES - RESULTS OF FIRST PROSPECTIVE STUDY. *N.P. Verma, M.J. Yusko, B.J. Beranek-McClung, L.A. Wil l iams. Neurology, Research and Audiology Services, Al len Park VAMC, Al len Park, MI 48101 USA**

We have recent ly completed the analysis of 92 subjects prospect ive ly studied to va l ida te the cont rovers ia l c o r t i c a l / subcor t ica] d i s t i n c t i o n . The resu l ts are in l ine wi th our pre- l im inary analys is published l as t year (NNBN 2:21-30, 1989).

Twenty-one normal subjects , 20 non-demented pa t ien t con t ro l s , 29 subjects wi th dementia and motor ic mani festat ions (DEM M+) and 22 subjects wi th dementia but no motor ic mani festat ions (DEM M-) were studied. Al l groups were matched fo r age, sex and education. The 2 dementia groups were matched for sever i t y o f dementia on the Matt is Scale and depression on the Hamilton Scale. The Dem M+ group and non-demented pat ien t contro l group were matched for abnormal motor scores on Columbia Unif ied Parkinson's Scale, AIMS and f inger - tapp ing . Those with Hachin- ski scores ~7, pos i t i ve VDRL, severe dementia, s i g n i f i c a n t head i n j u r y , seizure d isorder , h i s to ry o f MS or s i g n i f i c a n t premorbid psych ia t r i c history were excluded. Neuropsychological tasks included tests fo r mental speed (Stroop Naming and Reading), simple f ree r e c a l l , shor t - term memory scanning (Sternberg Paradigm), language (Western Aphasia ba t t e r y ) , naming (Boston Naming), pa r ie ta l lobe funct ions (St ick Construct ion, Line Or ien ta t ion , Prax is , R/L Discr iminat ion) and cogn i t i ve f l e x i b i l i t y (Stroop In te r fe rence ) .

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254 NEUROBIOLOGY OF AGING. VOLUME I l, 1990 ABSTRACTS OF SECOND INTERNATIONAL CONFERENCE ON ALZHEIMER'S DISEASE

CLINICAL COURSE

The mental speed was s i g n i f i c a n t l y slowed in Dem H~ group and was not accounted fo r by t he i r motor problems as non-de- mented pat ient controls did not show that degree of s|owing. Dem M+ also exhib i ted the greatest improvement of naming with semantic cueing.

These data support the co r t i ca l / subcor t i ca l d i s t i nc t ion at least in mi ld-to-moderately demented subjects and agree with the e lect rophys io log ica l data previously published (Goodin and Ami- no f f 1986, 1987; Verma et al 1989).

**This research was supported by the Veterans Administrat ion

HETEROGENEITY OF "PROBABLE ALZHEIMER'S DISEASE". *K. Blennow, A. Wallin, C.G. Gottfries. Department of Psychiatry and Neurochemistry, Gothenburg University, S-422 03 Hisings Backa, Sweden.

In 31 early-onset and 44 late-onset Alzheimer's disease (AD) patients, evaluations of the most pronounced symptomatology were made. Vascular factors (mild hypertension, mild ischemic heart disease and mild non-insulin-dependent diabetes) were recorded. The blood-brain barrier (BBB) function was measured using the albumin ratio (CSF-albumin/serum-albumin). CT-scans were reviewed with regard to leuko-araiosis (LA).

Among mildly demented patients, no regional symptomatology had developed; memory deficits, together with mild cognitive dysfunction, predominated. In the following, only moderately to severely demented patients are discussed.

When dividing the material strictly according to age at onset, parietal-lobe symptoms predominated in early-onset AD (93% of patients). In late-onset AD, non-regional symptomatology (74% of patients) dominated, while parietal-lobe symptomatotogy was less severe and less frequent. Vascular factors and LA were more frequent in late- than in early-onset AD. The BBB function was found to be related to vascular factors, assumed to coexist with AD.

AD, in typical cases, is characterized by temporo-parietal-lobe symptoms, and if the material is divided according to clinical symptomatology, two sub-groups of AD patients, fulfilling the NINCDS criteria for "probable AD", can be delimited. One group is characterized by higher age, presence of concomitant vascular diseases, BBB disturbance and non-regional symptomatology, together with absence of or mild parietal-lobe symptomatology. The other sub-group is characterized by lower age, absence of vascular diseases, normal BBB function, and a clinical picture of marked parietal-lobe symptomatology. The relation of these sub-groups to leuko-araiosis is discussed.

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RATE OF RK)(3qEOHON O F ~ OIOEASE AFR(NPECTMESKI)Y *Ugo Lucca, Mario Comelli', Mauro Tettemant~, Pietro Tirtboschi and Alberto Spsgnoli. "Mario Negri"Institute foe PhtrmacoloSical Research, Milan; • Department of Medical Statistios, University of Ptvia - Italy

A better understendin8 of the proB~ssien of ¢ O l ~ e and functional deterioration in Alzlw/mer's ~ (AD), beyond i m p r o v i ~ the knowledge of the tmtural history ot the i lhteu, could provide the bscksround for pre~ thin pstiont's rate of decline and h is lhe r future di~bi lRy, as wel l as help in i d ~ / ~ l possible subgroups end setting up a hendy end reUsble ~ e of evaluat ion of the eff icacy of a treatment.

With this aim, during a ~ Vial, we studied the ra te prosrass ien of 56 pat ients (meen age 74.5-+7.3) wi th a cl/nical dingnosis of AD in t r e a t m e n t wi th placebo,

In order to measure the rate of decline, and to mves~jate its possible correl~ien with =~e at onset, duration of the dlsoJm, and severity at fh'st examinstion, we used the Blessed Dementia

Scale (BDS) and the Blessed Information-Memory-Concentration (BIMC) Test as assessment tools, because scores on these tests have been found to correlate with the number of neuritic plaques

in post-mortem brain tissue of AD patients.

In our sample the mean annual rate of progression was 3.5

points at the BDS and 2.6 at the BIMC, with a large variability

among the subjects. The rate of deterioration of our patients is less

pronounced than that reported in other studies. This could be due either to a different population, studied, or to a "halo effect" of the clinical trial. However, even if Blessed is almost the only test used

to measure the rate of decline in the scanty literature on this topic,

the lack of standard procedures and the often incompleteness of

the data published make a meta-analytic approach to the results difficult.

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CLINICAL ASESSMENT OF MENTAL DECLINE IN ELDERLY PEOPLE. D. Cucinotta, A. Angeline+, P. Bonati ̂ , R. Palmirani, G. Savorani. Divisions of Geriatric Medicine Hospitals of Bologna, Forli+, Reggio E. ̂ , ITALY.

The inadequacies of the traditional approach to measuring mental decline of elderly people is evident. There is an essential need for additional methods for the evaluation of the degree of the impairment and follow-up. A new simple scale has been constructed and validated by our group. It is divided into five clusters of items, which are supposed to estimate cognition, personal interrelationship, affective disorders, apathy, somatic complaints. Both clusters and items are differently estimated according to relative clinical importance, to improve as much as possible the internal coherence of the scale. Maximum cumulative score is i00, minimum 0.

Total score of four items which explore cognition may range 0 to 45, of four items about personal interrelationship 0 to Ii, of three items about affective disorders - to 15, of four items about apathy 0 to 20, of three items about somatic complaints 0 to 9. These four degrees of the entity of each symptom are considered in the evaluation: absent mild, moderate, severe.

The reliability and the validity of this scale was tested and the results show that this instrument can be useful for a general diagnosis of decline and also monitoring both clinical efficacy of treatment and natural history of mental impairment in the elderly.

EMOTIONAL DISTURBANCES IN PATIENTS WITH ALZHEIMER'S DISEASE. " C. Derouasr~. C. Bunganer, R. Jouvent. H6pital de la Salp4Rd~re, Paris, France.

The aim of the study was to describe the emotion~ pattoms-of patlants with Alzl~_.imer's disease, AD, and to find oLq if there was troy ratMIonShtl~ between these pattmlls and noWdth~ ~ . Sixty o u t ; ~ f l ~ th~NINCDS- ADRDA criteria for ~ or pmmible AD, were asSsesedf0r m0od cftmm~nces in a semtstructured Intendew. In the first part of the study, mood w u assessed according to the umlat nosograplllc approach, using Ostd-lll criteria for major depressive episode and generalized anxiety. Delm'essive and anxious symptomatology were evlduatod ~ Halnilton ~ Rating Scale. HDRS, Mor, m n w y - , ~ e ~ Per.moon mm~o sots, M,mRS, Ty. . ~ Sin,e, COW a n x ~ rating scale. In the se¢ol¢l ~ of the study, a c c o r ~ to a dlmonatorml approach, heterogenoIty of the emotional behavlour was messed with the Depreuive Mood Scale (Jouvent et at, 1gin) to pothto~dlWe,~t'sdimeneions of mood. Cognitive deEm~s were assessed by the Mint-Mental State EXamination, MMS (Fofste~ and the Dement~ RMMg Scale, ORS (Maflb).

The 60 i~tient8 wore 23 n, latN and 37 tomatas, moan a0e wos 71,6d:7. 34 paints ixe~ntKI with an ~ ormlt and26 ~ a ~tP~eet AD, Mean du~allon of the d isem was 4.4:1:2.4 yearS. 23 I~ttents had a mild domeNie (MMS score-24.4+ 2.7; DRS score= 116.4+11,3); 30 a moderate (MMS- 16.7i-2.2; DRS=98.7+15.6); and 7 a severe d e ~ (blMS-7.6d:Z,4; ~ . 9 ~ , 2 1 ) .

Part I: None of the 60 palienls met the DSM-Ill ¢dBrla for Major Depressive Episode. The mean HORS loom was 8*4.2 (range 1-19), the n'4anMAOR$. 10.3¢-6.7 (0-26). MADRS soore, but no~ HDRS sco~, was stgrdflca~lycorrekited with MMS score (r-.33) but not with the DRS soots no[with the c~retton of the disaase. None of the patients met the DSM-III crlteda ~ Generalized Anxiety Dlasrdor. Tyrer score, but not COVI score, was 810ntlica~ly ¢ i with the DRS score (r-.31) and the duration of the,¢lleesse (r=-.28). Thus depreuiva end anxiety symptoms were more pronounced in mild dementia than In mnderate or severe dementia.