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Alzheimers Dement. 2017 Dec;13(12):1307-1316. doi: 10.1016/j.jalz.2017.04.011. Epub 2017 Jun 15.

Incidence of cognitively defined late-onset Alzheimer's dementia subgroups from a prospective cohort study.

Author information

1
Department of Medicine, University of Washington, Seattle, WA, USA. Electronic address: pcrane@uw.edu.
2
VA Puget Sound Health Care System, Geriatric Research Education and Clinical Center, Seattle, WA, USA; Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA.
3
Department of Medicine, University of Washington, Seattle, WA, USA.
4
Department of Radiology and Imaging Sciences and the Indiana Alzheimer's Disease Center, Indiana University School of Medicine, Indianapolis, IN, USA.
5
Kaiser Permanente Washington Health Research Institute, Seattle, WA, USA.
6
Department of Psychosocial and Community Health, University of Washington, Seattle, WA, USA.
7
Department of Neurology, Swedish Medical Center, Seattle, WA, USA.
8
Department of Radiology, University of Washington, Seattle, WA, USA; Department of Neurology, University of Washington, Seattle, WA, USA.
9
College of Arts and Sciences, University of Washington, Seattle, WA, USA.
10
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
11
Department of Pathology, University of Washington, Seattle, WA, USA.
12
VA Puget Sound Health Care System, Geriatric Research Education and Clinical Center, Seattle, WA, USA; Department of Neurology, University of Washington, Seattle, WA, USA.
13
Department of Neurology, Boston University School of Medicine, Boston, MA, USA.

Abstract

INTRODUCTION:

There may be biologically relevant heterogeneity within typical late-onset Alzheimer's dementia.

METHODS:

We analyzed cognitive data from people with incident late-onset Alzheimer's dementia from a prospective cohort study. We determined individual averages across memory, visuospatial functioning, language, and executive functioning. We identified domains with substantial impairments relative to that average. We compared demographic, neuropathology, and genetic findings across groups defined by relative impairments.

RESULTS:

During 32,286 person-years of follow-up, 869 people developed Alzheimer's dementia. There were 393 (48%) with no domain with substantial relative impairments. Some participants had isolated relative impairments in memory (148, 18%), visuospatial functioning (117, 14%), language (71, 9%), and executive functioning (66, 8%). The group with isolated relative memory impairments had higher proportions with ≥ APOE ε4 allele, more extensive Alzheimer's-related neuropathology, and higher proportions with other Alzheimer's dementia genetic risk variants.

DISCUSSION:

A cognitive subgrouping strategy may identify biologically distinct subsets of people with Alzheimer's dementia.

KEYWORDS:

Alzheimer's disease; Cognition; Endophenotypes; Genetics; Heterogeneity; Neuropathology; Subgroups

PMID:
28623677
PMCID:
PMC5723557
DOI:
10.1016/j.jalz.2017.04.011
[Indexed for MEDLINE]
Free PMC Article

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