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Early organiform impairment test (OFIT). A new performance test for assessment of early cognitive impairment
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1.Original Clinical Studies
Pmg. Neum-Psychophomncol. 6 Eliol. Psychiot Printed in Great Britain. All rights reserved.
1985. Vol. 9. pp. 575-579
Copyright
027&5fJ46/85 $0.00 + so @ 1985 Pergamon Press Ltd.
EARLY ORGANIFORM IMPAIRMENT TEST (OFIT). A NEW PERFORMANCE TEST FOR ASSESSMENT OF EARLY COGNITIVE IMPAIRMENT
MOHAMMED M. AMIN, PARVEEN KHAN, HEINZ E. LEHMANN and JAMAL MIRMIRAN 2 1 Division of psychopharmacology,McGill University and The Lakeshore General Hospital, Montreal, Quebec, Canada
(Final form, June 1985)
Abstract Amin, Mohammed M., Parveen Khan, Heinz E. Lehmann and Jamal Mirmiran: Early organiform impairment test (OFIT). A new performance test for assessment of early cognitive impairment. Prog. Neuro-Psychopharmacol.L Biol. Psychiat. 1985, 2 (5/6): 575-578. 1.
2.
3. 4.
No satisfactory tests are available to a) document and b) monitor the short term effects of various pharmacological agents on early, and hopefully reversible, organic cognitive impairment in otherwise healthy individuals. A new test battery, Organiform Impairment Test (OFIT), is based on the clinical observation that impairment of the ability to operate simultaneouslywith a number of mental sets and stimuli is one of the first clinical manifestations in the early stages of organic brain pathology. This battery can be administered in 20-30 minutes and is partly automated. It has been standardized on 167 normal subjects in age ranges from 15 to 80 years. Any score below 50 on the battery in subjects under 80 years of age should be regarded with suspicion.
Keywords: Alzheimer's Disease, cognition, nootropic, organiform impairment, reversibility, test battery. Abbreviations: Alzheimer's Disease (AD), Organiform Impairment Test (OFIT)
Introduction When the clinical diagnosis of Alzheimer's Disease (AD) is first made, family members frequently remark that process had. really _.the . dementing __ . ._ __ started one or two years earlier. It is at that - not clinically recognizable - time of the earliest stages of AD that any therapeutic attempts with pharmacologicalor metabolic interventionwould have their greatest chances of success. However, there is, at the present time, no clinical or instrumental procedure that will reliably distinguish between the cognitive impairment that is an effect of normal aging (senescence) and the earliest pathological stages of Alzheimer's Disease (Jolles and Hijman, 1982; J.P. Schaie and K.W. Schaie, 1982). Most of the existing scales for the clinical assessment of mental aging and cognitive impairment are restricted to the assessment of various degrees of dementing process after it has already been clinically diagnosed (H.S. Wang, 1977). The OFIT is aimed at the recognition of pathological, cognitive impairment at the earliest stages of a dementing process that is assumed to be primarily caused by organic, i.e. structural, brain changes.
Methods The Test Battery: The OFIT was constructed so as to reflect those cognitive and performance changes often thought of as the earliest manifestations of a pathological decline of intellectualpowers,
575
576
M. M. Amin et al.
e.g.
slowing of reaction time and performance, impairment of abstract thinking, concentration, short-term memory,vigilance and the ability to perform several acts simultaneously, as well as increased susceptibility to the disturbing influence of distracting stimuli (M. Kinsbourne, 1977). Organiform cognitive impairment is assessed through a sequence of psychomotor tasks consisting of: decoding of symbols into numbers, calculation involving addition and subtraction, cancellation of digits, simple visual reaction time, card sorting. The subject is given instructions regarding the entire sequence before the test begins. He is also given a practice trial. Scores are expressed as: Total time taken for the test, number of rows correctly decoded, number of rows not decoded, number of omissions, number of incorrect cancellations,mean visual reaction time to light stimulus, failure to respond to light stimulus, number of cards upturned, failure to upturn cards, nuuber of cards correctly placed, number of cards incorrectly placed, failure to remember sequence (i.e. number of times S asks E "what to do next" after the practice trial). Length of session: 15-20 minutes. Apparatus: a> 1 table; b) 2 chairs; c) 2 pencils; d) a stopwatch; e) a sheet of paper with 10 rows of symbols, each row consisting of 8 symbols interlinked by either a plus or a minus sign; f) a sheet of paper with 10 rows of digits, each row consisting of 35 digits; g) a pack of 30 stimulus cards arranged according to a predetermined order.
Age sensitivity of scores This non-verbal performance test battery is highly sensitive to age-induced changes. Figure 1, giving mean scores, reflects the age induced decline of performance of the OFIT according to 10 year groupings in a total sample of 167 volunteer subjects who were not str-
21'30
31'LO 11150 51'60 61'70 71%0 Age Range 0 Mean Score ot 6 AD Patients
Fig. 1. OFIT scores in normal controls : Total N=167 and AD patients : Total N= 6
Early organiform impairment test
577
atified according to social status, education or I.Q. and were not known to manifest any psychiatric symptoms. The gradient of reduction in performance is fairly continuous between the second and eighth decades of life. It suggests that a score below 50 at any age before g0 should be regarded with suspicion.
a
Pretreatment
Piracetam
1
80
Fig. 2.
*
Mean OFIT scores of the entire experimental population (N=30) during the clinical trial with a nootropic drug
70 60 v1 z
50
: 40 30 20 IO v3 Fig.
3. Mean OFIT scores of the low scorers (OFIT(70) during Clinical Trial
Fig.
4.
0L Mean OFIT scores of the high scorers (OFIT)70) during Clinical Trial
M. M. Amin
578
Example
of
et
application
at.
in clinical
trial
An 18 week, double-blind clinical trial with Piracetam in a group of 30 subjects, aged 4?70, who carried no clinical diagnosis and continued to function but complained of gradually . . ._ increasing impairment of energy level, powers of concentration, memory and vigilance, revealed the potential of OFIT not only as a parameter of therapeutic change, but also as a criterion for pre-trial selection of subjects. As shown in Fig. 2, when the mean pre-trial (baseline) OFIT score of the whole group is compared with the mean scores after placebo and after Piracetam treatment, there appears a statistically significant improvement following Piracetam (p=
Conclusion If the OFIT is used as a diagnostic tool for the detection of pathological, age related, cognitive impairment before a clinical diagnosis of dementia can be established it may be possible to institute clinical trials of therapeutic intervention, by drugs or other agents, with the goal of arresting premature , senescent impairment or delaying the progress of cognitive decline in normal senescence. It might also permit, possibly by means of periodic testing, to detect progressive Alzheimer’s Disease in the very early stages, when trials of clinical interv@ntion might still have a chance of succeeding because structural changes in the brain have not yet become irreversible.
Acknowledgement These studies Pharmaceuticals
were supported in part (Piracetam Study).
by grants
from CIBA-GEIGY LTD.(No~als)
and Nordic
Regerences COLE, M. and DASTOOR, D.P.
(1983
JOLLES, J. and HUMAN, R. (1983) the Brain. W.H. Gispen and J.
Hierarchic
Dementia
Scale
“in
press”.
of aging and dementia. The neuropsychology Elsevier Science Traber (eds), pp 227-250.
(1977) Cognitive Decline with and Dementia, W. Lynn Smith and M. Kinsbourne New York, Inc.,
KINSBOURNE , M.
IN: Aging Publishers.
Advancing Age: An Interpretation. IN: (eds), pp 217-235. Spectrum Publications
of
Aging
SCBAIE, J.P. and SCRAIE, K.W. (1977) Psychological Evaluation of the Cognitively Cognitive & Emotional Disturbance in the Elderly, C. Eisdorfer Elderly. IN: Year Book Medical Publishers, Inc., London. Friedel (eds), pp 55-73.
Impaired and R.O.
WANG, H.S. (1977) Kinsbourne (eds),
and M.
Inquiries
Dementia pp l-24.
and reprint
of
Old Age. IN: Aging Spectrum Publications,
requests
Dr. M. Amin Department of Psychiatry Lakeshore General liospital 160 Stillview Road Pointe Claire, Quebec, Canada B9R 2Y2
should
be addressed
and Dementia, W. Lynn Smith Inc., New York,
to:
1.Original Clinical Studies
Pmg. Neum-Psychophomncol. 6 Eliol. Psychiot Printed in Great Britain. All rights reserved.
1985. Vol. 9. pp. 575-579
Copyright
027&5fJ46/85 $0.00 + so @ 1985 Pergamon Press Ltd.
EARLY ORGANIFORM IMPAIRMENT TEST (OFIT). A NEW PERFORMANCE TEST FOR ASSESSMENT OF EARLY COGNITIVE IMPAIRMENT
MOHAMMED M. AMIN, PARVEEN KHAN, HEINZ E. LEHMANN and JAMAL MIRMIRAN 2 1 Division of psychopharmacology,McGill University and The Lakeshore General Hospital, Montreal, Quebec, Canada
(Final form, June 1985)
Abstract Amin, Mohammed M., Parveen Khan, Heinz E. Lehmann and Jamal Mirmiran: Early organiform impairment test (OFIT). A new performance test for assessment of early cognitive impairment. Prog. Neuro-Psychopharmacol.L Biol. Psychiat. 1985, 2 (5/6): 575-578. 1.
2.
3. 4.
No satisfactory tests are available to a) document and b) monitor the short term effects of various pharmacological agents on early, and hopefully reversible, organic cognitive impairment in otherwise healthy individuals. A new test battery, Organiform Impairment Test (OFIT), is based on the clinical observation that impairment of the ability to operate simultaneouslywith a number of mental sets and stimuli is one of the first clinical manifestations in the early stages of organic brain pathology. This battery can be administered in 20-30 minutes and is partly automated. It has been standardized on 167 normal subjects in age ranges from 15 to 80 years. Any score below 50 on the battery in subjects under 80 years of age should be regarded with suspicion.
Keywords: Alzheimer's Disease, cognition, nootropic, organiform impairment, reversibility, test battery. Abbreviations: Alzheimer's Disease (AD), Organiform Impairment Test (OFIT)
Introduction When the clinical diagnosis of Alzheimer's Disease (AD) is first made, family members frequently remark that process had. really _.the . dementing __ . ._ __ started one or two years earlier. It is at that - not clinically recognizable - time of the earliest stages of AD that any therapeutic attempts with pharmacologicalor metabolic interventionwould have their greatest chances of success. However, there is, at the present time, no clinical or instrumental procedure that will reliably distinguish between the cognitive impairment that is an effect of normal aging (senescence) and the earliest pathological stages of Alzheimer's Disease (Jolles and Hijman, 1982; J.P. Schaie and K.W. Schaie, 1982). Most of the existing scales for the clinical assessment of mental aging and cognitive impairment are restricted to the assessment of various degrees of dementing process after it has already been clinically diagnosed (H.S. Wang, 1977). The OFIT is aimed at the recognition of pathological, cognitive impairment at the earliest stages of a dementing process that is assumed to be primarily caused by organic, i.e. structural, brain changes.
Methods The Test Battery: The OFIT was constructed so as to reflect those cognitive and performance changes often thought of as the earliest manifestations of a pathological decline of intellectualpowers,
575
576
M. M. Amin et al.
e.g.
slowing of reaction time and performance, impairment of abstract thinking, concentration, short-term memory,vigilance and the ability to perform several acts simultaneously, as well as increased susceptibility to the disturbing influence of distracting stimuli (M. Kinsbourne, 1977). Organiform cognitive impairment is assessed through a sequence of psychomotor tasks consisting of: decoding of symbols into numbers, calculation involving addition and subtraction, cancellation of digits, simple visual reaction time, card sorting. The subject is given instructions regarding the entire sequence before the test begins. He is also given a practice trial. Scores are expressed as: Total time taken for the test, number of rows correctly decoded, number of rows not decoded, number of omissions, number of incorrect cancellations,mean visual reaction time to light stimulus, failure to respond to light stimulus, number of cards upturned, failure to upturn cards, nuuber of cards correctly placed, number of cards incorrectly placed, failure to remember sequence (i.e. number of times S asks E "what to do next" after the practice trial). Length of session: 15-20 minutes. Apparatus: a> 1 table; b) 2 chairs; c) 2 pencils; d) a stopwatch; e) a sheet of paper with 10 rows of symbols, each row consisting of 8 symbols interlinked by either a plus or a minus sign; f) a sheet of paper with 10 rows of digits, each row consisting of 35 digits; g) a pack of 30 stimulus cards arranged according to a predetermined order.
Age sensitivity of scores This non-verbal performance test battery is highly sensitive to age-induced changes. Figure 1, giving mean scores, reflects the age induced decline of performance of the OFIT according to 10 year groupings in a total sample of 167 volunteer subjects who were not str-
21'30
31'LO 11150 51'60 61'70 71%0 Age Range 0 Mean Score ot 6 AD Patients
Fig. 1. OFIT scores in normal controls : Total N=167 and AD patients : Total N= 6
Early organiform impairment test
577
atified according to social status, education or I.Q. and were not known to manifest any psychiatric symptoms. The gradient of reduction in performance is fairly continuous between the second and eighth decades of life. It suggests that a score below 50 at any age before g0 should be regarded with suspicion.
a
Pretreatment
Piracetam
1
80
Fig. 2.
*
Mean OFIT scores of the entire experimental population (N=30) during the clinical trial with a nootropic drug
70 60 v1 z
50
: 40 30 20 IO v3 Fig.
3. Mean OFIT scores of the low scorers (OFIT(70) during Clinical Trial
Fig.
4.
0L Mean OFIT scores of the high scorers (OFIT)70) during Clinical Trial
M. M. Amin
578
Example
of
et
application
at.
in clinical
trial
An 18 week, double-blind clinical trial with Piracetam in a group of 30 subjects, aged 4?70, who carried no clinical diagnosis and continued to function but complained of gradually . . ._ increasing impairment of energy level, powers of concentration, memory and vigilance, revealed the potential of OFIT not only as a parameter of therapeutic change, but also as a criterion for pre-trial selection of subjects. As shown in Fig. 2, when the mean pre-trial (baseline) OFIT score of the whole group is compared with the mean scores after placebo and after Piracetam treatment, there appears a statistically significant improvement following Piracetam (p=
Conclusion If the OFIT is used as a diagnostic tool for the detection of pathological, age related, cognitive impairment before a clinical diagnosis of dementia can be established it may be possible to institute clinical trials of therapeutic intervention, by drugs or other agents, with the goal of arresting premature , senescent impairment or delaying the progress of cognitive decline in normal senescence. It might also permit, possibly by means of periodic testing, to detect progressive Alzheimer’s Disease in the very early stages, when trials of clinical interv@ntion might still have a chance of succeeding because structural changes in the brain have not yet become irreversible.
Acknowledgement These studies Pharmaceuticals
were supported in part (Piracetam Study).
by grants
from CIBA-GEIGY LTD.(No~als)
and Nordic
Regerences COLE, M. and DASTOOR, D.P.
(1983
JOLLES, J. and HUMAN, R. (1983) the Brain. W.H. Gispen and J.
Hierarchic
Dementia
Scale
“in
press”.
of aging and dementia. The neuropsychology Elsevier Science Traber (eds), pp 227-250.
(1977) Cognitive Decline with and Dementia, W. Lynn Smith and M. Kinsbourne New York, Inc.,
KINSBOURNE , M.
IN: Aging Publishers.
Advancing Age: An Interpretation. IN: (eds), pp 217-235. Spectrum Publications
of
Aging
SCBAIE, J.P. and SCRAIE, K.W. (1977) Psychological Evaluation of the Cognitively Cognitive & Emotional Disturbance in the Elderly, C. Eisdorfer Elderly. IN: Year Book Medical Publishers, Inc., London. Friedel (eds), pp 55-73.
Impaired and R.O.
WANG, H.S. (1977) Kinsbourne (eds),
and M.
Inquiries
Dementia pp l-24.
and reprint
of
Old Age. IN: Aging Spectrum Publications,
requests
Dr. M. Amin Department of Psychiatry Lakeshore General liospital 160 Stillview Road Pointe Claire, Quebec, Canada B9R 2Y2
should
be addressed
and Dementia, W. Lynn Smith Inc., New York,
to: