Determination of cut-off scores of the PAS
In the section selection of the variables of the PAS we described how the items of the PAS were
selected. We will now explain how we arrived at the cut-off score for each item.
The incidence of AD in the general population increases with age (Ott et al., 1998). The incidence
of AD in subjects younger than 60 years is very low in both epidemiological settings (Ott et al.,
1998; Rocca et al., 1986) and in clinical settings (Visser, 2000), and therefore subjects younger
than 60 are given a score of -1. The risk for AD increases steeply after age 75 in both
epidemiological settings (Geerlings et al., 1999; Ott et al., 1997; Rocca et al., 1986) and in clinical
settings (Visser, 2000), and for this reason subjects older than 75 years are given a score of 2.
Epidemiological data show an increase in incidence of AD after age 70 (Ott et al., 1998) but data
from the Maastricht Memory Clinic show an increase in incidence of AD already after age 65
(Visser, 2000). Because the data of the Maastricht Memory Clinic are based on subjects with mild
cognitive impairment, we chose to give subjects between 65 and 75 years a score of 1.
A MMSE score >= 28 is generally considered a normal score (e.g., Golomb et al., 1993) and for this
reason a MMSE score >= 28 is given a score of 0. A MMSE score <= 25 is associated with a high risk
for dementia in the general population and for this reason these scores are given a score of 2
(Braekhus et al., 1995). The remaining scores (26 and 27) are given a score of 1. Since the MMSE
score correlates with age and education, it should be corrected for these variables (Crum et al.,
1993; Tombaugh et al., 1992). For simplicity of scoring, we dichotomized the effect of age and
made the cut-off scores 1 point lower in subjects older than 75 years (Crum et al., 1993). The
effect of education was trichotomized (Crum et al., 1993; Maastricht Aging Study
, unpublished data). The cut-off score for subjects with a high level of
education ( >= 14 years) was made 1 point higher and the cut-off scores for subjects with a low level
of education (<= 8 years) was made 1 point lower than the proposed cut-off scores after correction
C. Functional impairment
Global Deterioration Scale (GDS) (Reisberg et al., 1982) stage 3, the Clinical Dementia Rating
scale (CDR) (Hughes et al., 1982) score of 0.5, and the diagnosis of minimal dementia (Roth et
al., 1986) are given a score of 2 because they are associated with a high risk of AD (Cooper et al.,
1996; de Leon et al., 1993; Devanand et al., 1997; O'Connor et al., 1991; Reisberg et al., 1986;
Rubin et al., 1989b). Memory complaints (which is equivalent to GDS stage 2) are less strongly
but still significantly associated with AD and is therefore given a score of 1 (Geerlings et al., 1999;
Schmand et al., 1996; Schofield et al., 1997).
D. Neuropsychological tests
Impairment is defined as a score below the 10th percentile (or above the 90th percentile for speed
related tests) according to age-, sex-, and education-corrected norms. If performance is impaired in
one test a score of 1 is given, if performance is impaired in two tests a score of 2 is given, and if
performance is not impaired in any test a score of 0 is given. Because memory impairment is the
most common symptom in the early stage of AD (Almkvist et al., 1998; Fox et al., 1998; Newman
et al., 1994; Nielsen et al., 1999; Small et al., 1997a), a score of -1 is given if memory
performance is above average regardless of the score on other tests.
E. Medial temporal lobe atrophy
Medial temporal lobe atrophy can be assessed by either volumetry of the hippocampus (both left
and right side) or qualitatively. The PAS rating of volume is based on percentile scores. Atrophy is
defined as a volume below the 10th percentile (z-score <= -1.28) and is given a score of 2. If the
volume is in the highest tertile (z-score >0.44), a score of -1 is given, if the volume is in the middle
tertile (z-score 0.44-0.44) a score of 0 is given, and if the volume is in the lowest tertile but above
the 10th percentile (-1.28 < z-score <= -0.44) a score of 1 is given. Qualitative rating should be
performed according to the method described by Scheltens et al. (1992) or de Leon et al. (1993a).
Both sides should be rated and the highest rating should be used for the PAS scoring. Both authors
take a qualitative rating >= 2 as an indicator of atrophy and therefore a rating >= 2 is given a score of 2.
A rating of 0 is given a score of 0 and a rating of 1 a score of 1. Since the qualitative rating
correlates with age (de Leon et al., 1997; Scheltens et al., 1992) the cut-off scores for subjects
older than 75 years are 1 point lower. Thus, in subjects older than 75 years a rating of 0 is given a
score of -1, a rating of 1 a score of 0, a score of 2 a rating of 1, and a rating of 3 or higher a score
F. Apolipoprotein E genotype
Carriers of the apolipoprotein (apoE) e3e4 genotype are given a score of 1. Carriers of the apoE
e4e4 genotype are given a score of 2 because the risk of AD is much higher in homozygotes than in
heterozygotes (Slooter et al., 1998). Data on whether subjects with the apoE-e2e4 genotype have
an increased risk of AD are inconclusive and therefore this genotype is given a score of 0.
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