Improving the Diagnosis of the Frontal Variant of Alzheimer’s Disease with the DAPHNE Scale

Abstract

Background: The frontal variant of Alzheimer’s disease (fAD) is poorly understood and poorly defined. The diagnosis remains challenging. The main differential diagnosis is the behavioral variant of frontotemporal degeneration (bvFTD). For fAD, there is some dissociation between the clinical frontal presentation and imaging and neuropathological studies, which do not always find a specific involvement of the frontal lobes. DAPHNE is a behavioral scale, which demonstrated excellent performance to distinguish between bvFTD and AD. Objective: The aim of the present study was to assess the reliability of this new tool to improve the clinical diagnosis of fAD. Methods: Twenty fAD patients and their caregivers were prospectively included and were compared with 36 bvFTD and 22 AD patients. Results: The three main behavioral disorders in the fAD patients were apathy, loss of empathy, and disinhibition. Three disorders were discriminant because they were less frequent and less severe in the fAD patients than in the bvFTD patients, namely hyperorality, neglect, and perseverations. This specific pattern of behavioral disorders was corroborated by SPECT or 18FDG PET-CT scan that showed that patients with fAD could have a medial frontal hypoperfusion, whereas in bvFTD patients the orbitofrontal cortex was the main involved region, with more diffuse hypoperfusion. Conclusion: We demonstrated that DAPHNE had good sensitivity and good specificity to discriminate between the three groups and in particular between fAD and bvFTD patients. DAPHNE is a quick tool that could help clinicians in memory clinics not only to differentiate bvFTD from typical AD but also from fAD.

Research Criteria for the Behavioral Variant of Alzheimer Disease

“…The systematic literature search yielded 1257 records, of which 116 studies were assessed at full-text level for eligibility and 83 studies met inclusion criteria (eFigure 5 in the Supplement for flowchart). Confirmation of AD pathology was present in 91.1% of cases with bvAD based on autopsy data (36 studies; n = 334), genetic data (9 studies; n = 21), or biomarker data (31 studies; n = 262), while no information was available in 9.9% of cases (11 studies including 68 cases of bvAD). Thirteen studies were eligible for meta-analysis.…”

“…Meta-analysis was used to examine whether bvAD differed from tAD and bvFTD in terms of behavioral/neuropsychiatric and neuropsychological features and bvAD differed from tAD in the distribution of amyloid-β and tau pathology defined at autopsy. Missing data were requested from the authors of 3 studies (and all 3 responded) . We calculated the pooled standardized mean differences and 95% CIs using Hedges g random-effects models in the “meta” package of R version 4.0.2 (R Foundation for Statistical Computing), with a significance level of P < .05.…”

Provisional research criteria for the behavioral variant of Alzheimer’s disease A systematic review and meta-analysis

“…bvAD did not differ from tAD in three studies 23,26,27 , and showed moderately more involvement of frontal regions in bvAD compared to tAD in three other studies 17,24,25 . Studies assessing glucose metabolism with [ 18 F]FDG-PET or perfusion with SPECT (k=7, n=88) also showed heterogeneous results, ranging from a predominantly temporoparietal hypometabolic pattern 27,28 to a mixed frontal and temporoparietal 15,16,29,30 or predominantly frontal pattern 31 . Amyloid-PET studies (k=2, n=28) showed no differences in amyloid-β burden or distribution between bvAD and tAD patients.…”

“…Missing data were requested from the authors of three studies (3/3 responded). [15][16][17] We calculated the pooled standardized mean differences and 95% confidence intervals using Hedges' g random-effects models in the "meta" package (R v4.0.2), with significance levels of p<0.05. We used random effects because we assumed that the true effect size would be study dependent, due to high heterogeneity in samples, methodology and outcomes among studies.…”

Diagnosis of frontotemporal dementia: recommendations of the Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy of Neurology

“…The DAPHNE scale 63 is based on the bvFTD diagnostic criteria 6 and on the FBI items. There is only one study to evaluate its application in the differential diagnosis between bvFTD and AD (frontal variant), with good clinical accuracy 64 . There is no Brazilian validation or translation of this scale, but it appears to be promising.…”