Poster Presentation: Alzheimer’s Disease and K&ted Dementius IV

rexding in a nursing home. This open-label study was conducted at 13 US centers.

involving 173 AD patients (65-97 years of age). The patients were titrated to a dose

of 3-12 mg/day rivastigmine and the primary efficacy measure, the Neuropsychiatric

Inventory - Nursing Home version (NPI-NH), was used to evaluate behavioral

symptoms (e.g.. agitation, apathy, hallucinations, delusions) at I2 and 26 weeks. The

mean MMSE score at baseline was 9.2 and the mean NPI-NH score was 15.8, with

81% of patients having at least one behavioral symptom. All patients who entered had

a coexistent medical condition and were taking concomitant medicationa. After 26

weeks of treatment, there was a mean reduction in NPI-NH total score of 3.25 points

(20%:). For patients with behavioral symptoms at baseline, who completed 26.weeks

of treatment. 58% demonstrated improvement, with 50%’ showing an improvement of

at least 30%. Behavioral improvement was also accompanied by a significant

decrease in the use of psychotropic medications. In nddltion, there was a concomitant

lmprovemrnt of 0.5 points in the MMSE mean change wore from bazline for the

entire population. Thl\ study provider ewdence that treatment with nvastigmine can

lead to behavioral Improvementa m AD patirntr to a degree which is similar to that

seen with commonly use’d armpsychotics, with the added advantage that II can

improve cogmtion.

SlOO~lNTERACTlONS WITH TAU IN ALZHEIMER’S DISEASE

AND THE ANALYSIS OF CHEMICAL PROPERTIES REQUIRED.

SIOOPP a hmall molecular &lght calcium and zinc bmding protein whose expression

i\ increased m AlLheimer’q d~seeae (AD). We have investigated aspect, of the

potential mteractionc of SlOOPand tau. Tau. a microtubule associated protein, can be

pho\phorylated which lead? to the formation of neurofibrillary tangles. il major

pathological factor in Allheimcr’s dieaw. Preview studies have identified S l(X@a\

a potentxd binding protein and our work examines variow factors that alter its

interaction with tau. We have observed that SlOO@bindmg to tau liom AD bran

homogenates I\ Ggnificantly reduced. Thi\ binding is blocked by the presence of

EDTA, a potent metal chelator. These rxperiments Identify the conditions required for

the binding of tau and SIOOP. and provide5 insight into the role they may play in the

pathophysiology of AlLheimer‘s disease.

(1005( GLOBAL INTELLECTUAL DETERIORATION IN PATIENTS WfTH ALZHEIMER’S DISEASE - THE REVERSE OF THE

MODEL OF INTELLECTUAL DEVELOPMENT: A PROPOSAL OF A “G RELATIONSHIP” USING THE BINET SCALE AND PET

Intellectual dcteriomtlon in patxnta with Al/heimer‘s dircar (AD) can tx comidered

to drmonatrate u reverse of the intellectual development of children, not attributable

to impaired specific cognitwe domams. We investigated the applicability of the

Tanaka-Binet Intelligence rcalc (TB xale): it has been established based on the

hypothesis showing a fundamental faculty of intelligence not attributable to a \peufic

domam. The scale was reported to be correlated with the tasks determining Piaget’c

developmental \tagrs. In Part I of this study, thirty AD patients and thirty

age-matched normal sub.jectb were examined with the wde. It wa\ possible to

quantitatively axe the intellectual function of the AD patient< even in the severe

age, although their 1Qs could not be abaessed with.thc WAlS. The findings appeared

to indicate a “general factor” of intellectual development mcluding three develop-

mental stage\ of Piaget. We conGder that the TB scale i\ useful m aaie,sing the

intellectual function in AD patirntr. In Part 11 of the study. we examined thirteen AD

patients with PET (positron rmiwon tomography). We found that the mean CMRglc

(cerebral metabolic rate for glucose) values declined in three stages and that the IQ

with the TB scale was correlated with CMRglc in widepread regions. The results

suggest that intellectual deterioration in AD patients may be based on widespread

region,, supporting the developmental and general intelligence model. Together with

the results of our previous study, we propose a “g relationship” based on a Piaget’s

model.

(1006)

s22 I

DEFICITS OF VISUOSPATIAL ATTENTION ABH,ITY IN PA- TIENTS WITH ALZHEIMER’S DISEASE AS SHOWN BY POSNER PARADIGM

Al7heirner‘s disease (AD) is a major cause of dementia in elderly adults. After an

Initial amnesic stage, attention may be the first non-memory domain to be affected ac

a relatively early stage before deficit\ in language and visuoapatial function become

apparent. We examined a \hlfting of visuo5patial attention in 20 patvents with

probable AD (NINCDS-ADRDA) and IO age-matched normal elderly subject5 by

choice reaction time (CRT) and the covert orienting paradigm. Neuropsychological

tests assearing home viwoapatial functions were also performed in the AD patient>.

For covert orienting, a peripheral spatial cue method vu teed, with stimulus-onset

(SOA) between the we and the target time varying from 250 mb to 2100 ms. The CRT

and the reaction times (RT?) for the valid condition\ were found to show no difference

between the AD and the normal group\ However. the RT\ cost, plus benefits were

found to be Ggnificantly greater in the AD patlenth than in the normal group. This

mpairment of shifting attention in the AD patients was not correlated with the

wverity of dementia. From the analysis of individual profile, in the time course of cue

validity. two wbgroups of AD patients were found, i.e., patienta who had a normal

pattern for the cue vahdity of the time courw. and thoce who had an abnormal,

‘extinction-hke’ pattern. The latter wbgroup had particular difficulty in performing

the visual construction and \patlal attention of neuropsychological test). These result\

wggested that focusing attention wa\ relatively intact even in moderate AD.

However, there was a subgroup of AD. conrihting of patients whew deficit5 of

‘disengagement were more severe, in which their voluntary shifting of attention may

also have been affected. Preview \tudles have uggested that the focwinp ot

viwo\patial attention vu\ intact hut that spatial shifting of attention to the contralilt-

rral field wa\ affected in nuld AD. We confirmed a smGlar pattern in more wvere AD

patient\. There wa\ an AD whgmup thowing an ‘ebnormal p~ltern‘ m tlmr course of

the ue validity. wggatmg a decline m voluntary shifts of attention. Thih whgrwp

\howcd impaumen~\ m nruropaych(,ll)gical tests on viwal construction and \patlal

attention.

(1007( A UNIFYING HYPOTHESIS OF ALZHEIMER’S DISEASE

Bard on the study of more than lOO.OW papers. a hoh\tlc. coherem hypothr\is I\

prcwnted uhich Inregrate\ neurohiologlcal. endocrinological and im~r~un,)lop,c:lI

flndingx into a comlxehzn\i\ c cauwl vxluencc ol c\ent\ leading 10 the mamfc~tat~on

ot Alrhcimrr’\ d~wa\e (AD). The theory defines AD a, a psych~,nzuroendocr~~~~)~

Immunolopul disorder in which the agin?-related impairmrnt c4 the ho~mwnal

regulation of the calcium-energy~redox homrosta\i\ i\ detcriomted by rl\k factors in

a prototypic gellr-ellV,rOnlllCIIt Interaction. Notnhly. this approach allows for the lirit

time to delineate cauwl relatlon$hlp~ between the major patho,phyGological went\

e.g. endocrinological aberrations. disruption of calcium, energy and rrdox homsorl;i-

\I\. APP and tau mctaboliw~, amyloid, nwro- trancmitter changes. cellular and

humoral immune re\pone\. apoE metaboh$m. neuronal plastuly. \ ulncrahiluy and

cell cycle events mcluding cell death. This highly innovntivc concept is a hrenk-

through 111 our underwndmg ot the p;lthophyslologlc;,I ha%\ of ncuro- degcnerati\ c

diwrdcrs and open\ up ~ne\u wenues for the precention and treatment of AD.

Comment (not to he Included m the puhli\hed nhaact) The complexity vt the rope

\e\crrly quatiow that the papa can he presented a\ a poster. Due to the complexity.

the topic I\ published a\ it w-is\ of 5 paper\ Paper\ I to 3 (already puhli$hcd, IC~IIIII,

mcluded in the package) contamed a total of ?SOO references. Paper 1 (not 4~”

whrnittedl M III drlinrate the cauwtlon and vxlurnce of c\enl\ m d highl) Inno\atl\ c

nnd unprecedented way and \LIII contam approx. 2000 additinn;d reference\. l?lrr 5

will outlrnr the conclusions for prevemion and treatment of the d~\e;tse.