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Alzheimers Res Ther. 2016 Feb 12;8:8. doi: 10.1186/s13195-016-0170-5.

Alzheimer's Disease Assessment Scale-Cognitive subscale variants in mild cognitive impairment and mild Alzheimer's disease: change over time and the effect of enrichment strategies.

Collaborators (466)

Weiner MW, Aisen P, Weiner M, Aisen P, Petersen R, Jack CR Jr, Jagust W, Trojanowki JQ, Toga AW, Beckett L, Green RC, Saykin AJ, Morris J, Shaw LM, Khachaturian Z, Sorensen G, Carrillo M, Kuller L, Raichle M, Paul S, Davies P, Fillit H, Hefti F, Holtzman D, Mesulam M, Potter W, Snyder P, Schwartz A, Green RC, Montine T, Petersen R, Aisen P, Thomas RG, Donohue M, Walter S, Gessert D, Sather T, Jiminez G, Balasubramanian AB, Mason J, Sim I, Beckett L, Harvey D, Donohue M, Jack CR Jr, Bernstein M, Fox N, Thompson P, Schuff N, DeCarli C, Borowski B, Gunter J, Senjem M, Vemuri P, Jones D, Kantarci K, Ward C, Jagust W, Koeppe RA, Foster N, Reiman EM, Chen K, Mathis C, Landau S, Morris JC, Cairns NJ, Householder E, Taylor-Reinwald L, Shaw LM, Trojanowki JQ, Lee V, Korecka M, Figurski M, Toga AW, Crawford K, Neu S, Saykin AJ, Foroud TM, Potkin S, Shen L, Faber K, Kim S, Nho K, Weiner MW, Thal L, Khachaturian Z, Thal L, Buckholtz N, Weiner MW, Snyder PJ, Potter W, Paul S, Albert M, Frank R, Khachaturian Z, Hsiao J, Kaye J, Quinn J, Silbert L, Lind B, Carter R, Dolen S, Schneider LS, Pawluczyk S, Beccera M, Teodoro L, Spann BM, Brewer J, Vanderswag H, Fleisher A, Heidebrink JL, Lord JL, Petersen R, Mason SS, Albers CS, Knopman D, Johnson K, Doody RS, Villanueva-Meyer J, Chowdhury M, Rountree S, Dang M, Stern Y, Honig LS, Bell KL, Ances B, Morris JC, Carroll M, Creech ML, Franklin E, Mintun MA, Schneider S, Oliver A, Marson D, Griffith R, Clark D, Geldmacher D, Brockington J, Roberson E, Love MN, Grossman H, Mitsis E, Shah RC, deToledo-Morrell L, Duara R, Varon D, Greig MT, Roberts P, Albert M, Onyike C, D'Agostino D 2nd, Kielb S, Galvin JE, Cerbone B, Michel CA, Pogorelec DM, Rusinek H, de Leon MJ, Glodzik L, De Santi S, Doraiswamy P, Petrella JR, Borges-Neto S, Wong TZ, Coleman E, Arnold SE, Karlawish JH, Wolk D, Clark CM, Smith CD, Jicha G, Hardy P, Sinha P, Oates E, Conrad G, Lopez OL, Oakley M, Simpson DM, Porsteinsson AP, Goldstein BS, Martin K, Makino KM, Ismail M, Brand C, Mulnard RA, Thai G, Mc-Adams-Ortiz C, Womack K, Mathews D, Quiceno M, Levey AI, Lah JJ, Cellar JS, Burns JM, Swerdlow RH, Brooks WM, Apostolova L, Tingus K, Woo E, Silverman DH, Lu PH, Bartzokis G, Graff-Radford NR, Parfitt F, Kendall T, Johnson H, Farlow MR, Hake AM, Matthews BR, Brosch JR, Herring S, Hunt C, van Dyck CH, Carson RE, MacAvoy MG, Varma P, Chertkow H, Bergman H, Hosein C, Black S, Stefanovic B, Caldwell C, Hsiung GY, Feldman H, Mudge B, Assaly M, Finger E, Pasternack S, Rachisky I, Trost D, Kertesz A, Bernick C, Munic D, Mesulam MM, Lipowski K, Weintraub S, Bonakdarpour B, Kerwin D, Wu CK, Johnson N, Sadowsky C, Villena T, Turner RS, Johnson K, Reynolds B, Sperling RA, Johnson KA, Marshall G, Yesavage J, Taylor JL, Lane B, Rosen A, Tinklenberg J, Sabbagh MN, Belden CM, Jacobson SA, Sirrel SA, Kowall N, Killiany R, Budson AE, Norbash A, Johnson PL, Obisesan TO, Wolday S, Allard J, Lerner A, Ogrocki P, Tatsuoka C, Fatica P, Fletcher E, Maillard P, Olichney J, DeCarli C, Carmichael O, Kittur S, Borrie M, Lee TY, Bartha R, Johnson S, Asthana S, Carlsson CM, Potkin SG, Preda A, Nguyen D, Tariot P, Burke A, Trncic N, Fleisher A, Reeder S, Bates V, Capote H, Rainka M, Scharre DW, Kataki M, Adeli A, Zimmerman EA, Celmins D, Brown AD, Pearlson GD, Blank K, Anderson K, Flashman LA, Seltzer M, Hynes ML, Santulli RB, Sink KM, Gordineer L, Williamson JD, Garg P, Watkins F, Ott BR, Querfurth H, Tremont G, Salloway S, Malloy P, Correia S, Rosen HJ, Miller BL, Perry D, Mintzer J, Spicer K, Bachman D, Finger E, Pasternak S, Rachinsky I, Rogers J, Kertesz A, Drost D, Pomara N, Hernando R, Sarrael A, Schultz SK, Ponto LL, Shim H, Smith KE, Relkin N, Chaing G, Lin M, Ravdin L, Smith A, Raj BA, Fargher K, Weiner MW, Aisen P, Weiner M, Aisen P, Petersen R, Green RC, Harvey D, Jack CR Jr, Jagust W, Morris JC, Saykin AJ, Shaw LM, Toga AW, Trojanowki JQ, Neylan T, Grafman J, Green RC, Montine T, Weiner M, Petersen R, Aisen P, Thomas RG, Donohue M, Gessert D, Sather T, Davis M, Morrison R, Jiminez G, Neylan T, Hayes J, Finley S, Harvey D, Donohue M, Jack CR Jr, Bernstein M, Borowski B, Gunter J, Senjem M, Kantarci K, Ward C, Jagust W, Koeppe RA, Foster N, Reiman EM, Chen K, Landau S, Morris JC, Cairns NJ, Householder E, Shaw LM, Trojanowki JQ, Lee V, Korecka M, Figurski M, Toga AW, Crawford K, Neu S, Saykin AJ, Foroud TM, Potkin S, Shen L, Faber K, Kim S, Nho K, Weiner MW, Friedl K, Schneider LS, Pawluczyk S, Beccera M, Brewer J, Vanderswag H, Stern Y, Honig LS, Bell KL, Fleischman D, Arfanakis K, Shah RC, Duara R, Varon D, Greig MT, Doraiswamy P, Petrella JR, James O, Porsteinsson AP, Goldstein B, Martin KS, Mulnard RA, Thai G, McAdams-Ortiz C, Mintzer J, Massoglia D, Brawman-Mintzer O, Sadowsky C, Martinez W, Villena T, Jagust W, Landau S, Rosen H, Perry D, Turner RS, Behan K, Reynolds B, Sperling RA, Johnson KA, Marshall G, Sabbagh MN, Jacobson SA, Sirrel SA, Obisesan TO, Wolday S, Allard J, Johnson SC, Fruehling J, Harding S, Peskind ER, Petrie EC, Li G, Yesavage JA, Taylor JL, Furst AJ, Chao S, Relkin N, Chaing G, Ravdin L.

Author information

1
Boehringer Ingelheim Pharma GmbH & Co. KG, Binger Strasse 173, Ingelheim/Rhein, 55218, Germany. jana.podhorna@boehringer-ingelheim.com.
2
Cogitars GmbH, Heidelberg, Germany. tillmann.krahnke.ext@boehringer-ingelheim.com.
3
Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach/Riss, Germany. michael.shear@boehringer-ingelheim.com.
4
VU University Medical Center Amsterdam, Amsterdam, The Netherlands. johncpc@btinternet.com.

Abstract

BACKGROUND:

Development of new treatments for Alzheimer's disease (AD) has broadened into early interventions in individuals with modest cognitive impairment and a slow decline. The 11-item version of the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) was originally developed to measure cognition in patients with mild to moderate AD. Attempts to improve its properties for early AD by removing items prone to ceiling and/or by adding cognitive measures known to be impaired early have yielded a number of ADAS-Cog variants. Using Alzheimer's Disease Neuroimaging Initiative data, we compared the performance of the 3-, 5-, 11- and 13-item ADAS-Cog variants in subjects with early AD. Given the interest in enrichment strategies, we also examined this aspect with a focus on cerebrospinal fluid (CSF) markers.

METHODS:

Subjects with mild cognitive impairment (MCI) and mild AD with available ADAS-Cog 13 and CSF data were analysed. The decline over time was defined by change from baseline. Direct cross-comparison of the ADAS-Cog variants was performed using the signal-to-noise ratio (SNR), with higher values reflecting increased sensitivity to detect change over time.

RESULTS:

The decline over time on any of the ADAS-Cog variants was minimal in subjects with MCI. Approximately half of subjects with MCI fulfilled enrichment criteria for positive AD pathology. The impact of enrichment was detectable but subtle in MCI. The annual decline in mild AD was more pronounced but still modest. More than 90 % of subjects with mild AD had positive AD pathology. SNRs were low in MCI but greater in mild AD. The numerically largest SNRs were seen for the ADAS-Cog 5 in MCI and for both the 5- and 13-item ADAS-Cog variants in mild AD, although associated confidence intervals were large.

CONCLUSIONS:

The possible value of ADAS-Cog expansion or reduction is less than compelling, particularly in MCI. In mild AD, adding items known to be impaired at early stages seems to provide more benefit than removing items on which subjects score close to ceiling.

PMID:
26868820
PMCID:
PMC4751673
DOI:
10.1186/s13195-016-0170-5
[Indexed for MEDLINE]
Free PMC Article

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