Refining Mild-to-Moderate Alzheimer Disease Screening: A Tool for Clinicians.
Recent evidence suggests that a substantial minority of people clinically diagnosed with probable Alzheimer disease (AD) in fact do not fulfill the neuropathological criteria for the disease. A clinical hallmark of these phenocopies of AD is that these individuals tend to remain cognitively stable for extended periods of time, in contrast to their peers with confirmed AD who show a progressive decline. We aimed to examine the prevalence of patients clinically diagnosed with mild-to-moderate AD who do not experience the expected clinically significant cognitive decline and identify markers easily available in routine medical practice predictive of a stable cognitive prognosis in this population.



Data were obtained from two independent, longitudinal, observational multicenter studies in patients with mild-to-moderate AD.



The two studies were the European "Impact of Cholinergic Treatment Use" (ICTUS) and the French "REseau sur la maladie d'Alzheimer FRançais" (REAL.FR).



We used prospective data of 756 patients enrolled in ICTUS and 340 enrolled in REAL.FR.



A prediction rule of cognitive decline was derived on ICTUS using classification and regression tree analysis and then cross-validated on REAL.FR. A range of demographic, clinical and cognitive variables were tested as predictor variables.



Overall, 27.9% of patients in ICTUS and 20.9% in REAL.FR did not decline over 2 years. We identified optimized cut-points on the verbal memory items of the Alzheimer Disease Assessment Scale-Cognitive Subscale capable of classifying patients at baseline into those who went on to decline and those who remained stable or improved over the duration of the trial.



The application of this simple rule would allow the identification of dementia cases where a more detailed differential diagnostic examination (eg, with biomarkers) is warranted. These findings are promising toward the refinement of AD screening in the clinic. For a further optimization of our classification rule, we encourage others to use our methodological approach on other episodic memory assessment tools designed to detect even small cognitive changes in patients with AD.
Gérontopôle, Institute of Ageing, Toulouse University Hospital, Toulouse, France; "NeuroToul" Center of Excellence in Neurodegeneration of Toulouse, Toulouse, France; Department of Psychiatry, University of Cambridge, Cambridge, England. Electronic address: nata.delcampo@gmail.com.
Natalia
N
Del Campo
Gérontopôle, Institute of Ageing, Toulouse University Hospital, Toulouse, France; INSERM UMR 1027, Paul Sabatier University of Toulouse, Toulouse, France.
Matteo
M
Cesari
Memory Clinic, Department of Neurology and Psychiatry, University Sapienza, Rome, Italy.
Marco
M
Canevelli
Gérontopôle, Institute of Ageing, Toulouse University Hospital, Toulouse, France; Department of Epidemiology & Biostatistics, EMGO+ Institute for Health and Care Research, VU University Medical Center, Amsterdam, the Netherlands.
Emiel O
EO
Hoogendijk
Gérontopôle, Institute of Ageing, Toulouse University Hospital, Toulouse, France; APHP, Department of Geriatrics, Bichat Hospital, Paris, France.
Matthieu
M
Lilamand
Gérontopôle, Institute of Ageing, Toulouse University Hospital, Toulouse, France.
Eirini
E
Kelaiditi
Gérontopôle, Institute of Ageing, Toulouse University Hospital, Toulouse, France; INSERM UMR 1027, Paul Sabatier University of Toulouse, Toulouse, France.
Maria E
ME
Soto
Gérontopôle, Institute of Ageing, Toulouse University Hospital, Toulouse, France.
Pierre-Jean
PJ
Ousset
Department of Veterans Affairs Medical Center, Center for Imaging of Neurodegenerative Diseases, San Francisco, CA; Department of Radiology, University of California, San Francisco, CA; Department of Medicine, University of California, San Francisco, CA; Department of Psychiatry, University of California, San Francisco, CA; Department of Neurology, University of California, San Francisco, CA.
Michael W
MW
Weiner
INSERM UMR 1027, Paul Sabatier University of Toulouse, Toulouse, France; Department of Epidemiology and Public Health, University Hospital Toulouse, Toulouse, France.
Sandrine
S
Andrieu
Gérontopôle, Institute of Ageing, Toulouse University Hospital, Toulouse, France; INSERM UMR 1027, Paul Sabatier University of Toulouse, Toulouse, France.
Bruno
B
Vellas
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000503:physiopathology*; D060825:Cognitive Dysfunction; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D009483:Neuropsychological Tests; D011446:Prospective Studies; D012720:Severity of Illness Index
Alzheimer disease; classification and regression tree (CART); cognitive decline; differential diagnosis