IMPORTANCE Increased prevalence of language-based learning disabilities (LDs) has been previously reported in patients with primary progressive aphasia (PPA). This study hypothesized that patients with focal neurodegenerative syndromes outside the language network, such as posterior cortical atrophy (PCA), would have a higher rate of nonlanguage LDs, congruent with their mainly visuospatial presentation. OBJECTIVE To investigate the prevalence and type of LD (language and/or mathematical and visuospatial) in a large cohort of patients with PCA compared with patients with logopenic variant PPA (lvPPA) and amnestic Alzheimer disease (AD). DESIGN, SETTING, AND PARTICIPANTS This case-control study reviewed 279 medical records from a university-based clinic and research center for patients with neurodegenerative diseases for LD history, including patients with PCA (n = 95), patients with lvPPA (n = 84), and a matched cohort with amnestic AD (n = 100). No records were excluded. The study compared cognitive and neuroimaging features of patients with PCA with and without LDs. A review of the records of patients presenting from March 1, 1999, to August 31, 2014, revealed 95 PCA cases and 84 lvPPA cases. Then 100 patients with amnestic AD from this same period were chosen for comparison, matching against the groups for age, sex, and disease severity. Data analysis was performed from September 8, 2013, to November 6, 2017. MAIN OUTCOMES AND MEASURES Prevalence of total LD history and prevalence of language and mathematical or visuospatial LD history across all cohorts. RESULTS A total of 179 atypical AD cases (95 with PCA and 84 with lvPPA) and 100 disease control cases (amnestic AD)were included in the study. The groupswere not statistically different for mean (SD) age at first visit (PCA, 61.9 [7.0] years; lvPPA, 65.1 [8.7] years; amnestic AD, 64.0 [12.6] years; P = .08), mean (SD) age at first symptom (PCA, 57.5 [7.0] years; lvPPA, 61.1 [9.0] years; amnestic AD, 59.6 [13.7] years; P = .06), or sex (PCA, 66.3%female; lvPPA, 56.0%female; amnestic AD, 57.0%female; P = .30) but differed on non-right-hand preference (PCA, 18.3%; lvPPA, 20.2%; amnestic AD, 7.7%; P = .04), race/ethnicity (PCA, 88.3%white; lvPPA, 99.0%white; amnestic AD, 80.0%white; P < .001), and mean (SD) educational level (PCA, 15.7 [3.2] years; lvPPA, 16.2 [3.3] years; amnestic AD, 14.8 [3.5] years; P = .02). A total of 18 of the 95 patients with PCA (18.9%) reported a history of LD, which is greater than the 3 of 100 patients (3.0%) in the amnestic AD cohort (P < .001) and the 10.0%expected rate in the general population (P = .007). In the PCA cohort, 13 of 95 patients (13.7%) had a nonlanguage mathematical and/or visuospatial LD; this ratewas greater than that in the amnestic AD (1 of 100 [1.0%]; P < .001) and lvPPA (2 of 84 [2.4%]; P = .006) cohorts and greater than the 6.0% expected general population rate of mathematical LD (P = .003). Compared with the patients with PCA without LDs, the group with LDs had greater preservation of global cognition and a more right-lateralized pattern of atrophy. CONCLUSIONS AND RELEVANCE Nonlanguage mathematical and visuospatial LDswere associated with focal, visuospatial predominant neurodegenerative clinical syndromes. This finding supports the hypothesis that neurodevelopmental differences in specific brain networks are associated with phenotypic manifestation of later-life neurodegenerative disease.
|Number of pages||10|
|State||Published - Jun 2018|
Bibliographical noteFunding Information:
Funding/Support: Dr Z. A. Miller is funded by grant K23 AG048291 from the National Institutes of Health (NIH). Dr Grinberg is funded by the John Douglas French Foundation and grants R01AG040311-01 and K24AG053435 from the NIH. Dr Seeley is funded by grant P50 AG1657303 from the NIH, the John Douglas French Alzheimer’s Disease Foundation, Consortium for Frontotemporal Dementia Research, James S. McDonnell Foundation, and Larry Hillblom Foundation. Dr B. L. Miller is funded by P50AG023501, P01AG019724, and P50 AG1657303 from the NIH and the state of California. Additional funds were provided by the Hellman Foundation and the Arking Foundation for Frontotemporal Dementia.
reported receiving grants from the Alzheimer’s Association and AVID Radiopharmaceuticals. Dr Seeley reported receiving support for travel from the Alzheimer’s Association and payment for lectures by the Alzheimer’s Association, American Academy of Neurology, and Novartis Korea. Dr B. L. Miller reported serving as a board member for the John Douglas French Alzheimer’s Foundation and Larry L. Hillblom Foundation; serving as a consultant for TauRx Ltd, Allon Therapeutics, Siemens, BMS, the Tau Consortium, and the Consortium for Frontotemporal Research; and receiving institutional support from Novartis. Dr Rabinovici reported receiving research support from Avid Radiopharmaceuticals, GE Healthcare, and Piramal Imaging and speaking or consulting fees from Eisai, Genentech, Lundbeck, Merck & Co, Putnam, and Roche. No other disclosures were reported.
© 2018 American Medical Association. All rights reserved.
ASJC Scopus subject areas
- Clinical Neurology