Practical cut‐offs for visual rating scales of medial temporal, frontal and posterior atrophy in Alzheimer's disease and mild cognitive impairment

Abstract

Background Atrophy in the medial temporal lobe, frontal lobe and posterior cortex can be measured with visual rating scales such as the medial temporal atrophy (MTA), global cortical atrophy – frontal subscale (GCA‐F) and posterior atrophy (PA) scales, respectively. However, practical cut‐offs are urgently needed, especially now that different presentations of Alzheimer's disease (AD) are included in the revised diagnostic criteria. Aims The aim of this study was to generate a list of practical cut‐offs for the MTA, GCA‐F and PA scales, for both diagnosis of AD and determining prognosis in mild cognitive impairment (MCI), and to evaluate the influence of key demographic and clinical factors on these cut‐offs. Methods AddNeuroMed and ADNI cohorts were combined giving a total of 1147 participants (322 patients with AD, 480 patients with MCI and 345 control subjects). The MTA, GCA‐F and PA scales were applied and a broad range of cut‐offs was evaluated. Results The MTA scale showed better diagnostic and predictive performances than the GCA‐F and PA scales. Age, apolipoprotein E (ApoE) ε4 status and age at disease onset influenced all three scales. For the age ranges 45–64, 65–74, 75–84 and 85–94 years, the following cut‐offs should be used. MTA: ≥1.5, ≥1.5, ≥2 and ≥2.5; GCA‐F, ≥1, ≥1, ≥1 and ≥1; and PA, ≥1, ≥1, ≥1 and ≥1, respectively, with an adjustment for early‐onset ApoE ε4 noncarrier AD patients (MTA: ≥2, ≥2, ≥3 and ≥3; and GCA‐F: ≥1, ≥1, ≥2 and ≥2, respectively). Conclusions If successfully validated in clinical settings, the list of practical cut‐offs proposed here might be useful in clinical practice. Their use might also (i) promote research on atrophy subtypes, (ii) increase the understanding of different presentations of AD, (iii) improve diagnosis and prognosis and (iv) aid population selection and enrichment for clinical trials.

Electroencephalography Is a Good Complement to Currently Established Dementia Biomarkers

“…Therefore, EEG is completely unbiased and without any circularity, and it still outperformed MTA. Similar sensitivity and specificity values have been reported for MTA, GCA-F and PA in the diagnosis of AD [26,27,42,43,44,45,46]. Only GCA-F showed some clinical utility for discriminating controls from all clinical patients, particularly from DLB/PDD patients, as recently shown [40].…”

“…L.C. has participated as single rater in seven previous independent studies, achieving intrarater agreement of weighted kappa values between 0.88 and 0.94 for MTA, of 0.70 for GCA-F, and of 0.72 for PA [6,25,27,28,29,30,31,32]. Good interrater agreement has previously been demonstrated for L.C.…”

“…However, this all depends on the cutoffs used for determining abnormality [6,48]. We used cognitive normative data from the NORD EEG cohort and applied a recently proposed cutoff for MTA [27]. This is still one of the main limitations of the IWG and NIA-AA diagnostic criteria at present.…”

“…material, see www.karger.com/doi/10.1159/000448394). Deviation from normality was established following a recently proposed list of practical cutoffs [27]. MTA was considered when MTA scores were ≥1.5, ≥1.5, ≥2.0, and ≥2.5 for the respective age ranges 45-64, 65-74, 75-84, and 85-94 years, and frontal atrophy and PA were considered when GCA-F and PA scores were ≥1, irrespective of age.…”

Measuring Global Brain Atrophy with the Brain Volume/Cerebrospinal Fluid Index: Normative Values, Cut-Offs and Clinical Associations

“…The BV/CSF index correlated with functions beyond episodic memory, suggesting that the index reflects the effect of processes leading to both global brain atrophy and disease-specific regional atrophy. Although regional atrophy in the medial temporal lobe is the main finding in AD and causes memory impairment [44], atrophy in other brain regions such as the frontal lobe and posterior cortex is also frequently reported [45,46]. Therefore, measurements that account for atrophy in brain regions other than the medial temporal lobe are important in AD [41].…”