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Introduction/aims Sporadic inclusion body myositis (IBM) is a degenerative and inflammatory acquired myopathy characterized by muscle deposition of various proteins typically associated with Alzheimer disease and other neurodegenerative diseases. Although cognitive impairment is not noted as a clinical feature of IBM, evidence is lacking. In this study we investigated whether cognitive performance of patients with IBM differs from population norms, focusing on cognitive domains affected in early Alzheimer disease (memory, executive function), and to test whether disease duration and the level of disability of IBM are associated with cognitive function. Methods Twenty-four patients with IBM (mean [standard deviation]: age, 62.0 [7.2] years; disease duration, 9.6 [4.8] years) were assessed cross-sectionally on neuropsychological tests covering multiple cognitive domains, including the Preclinical Alzheimer Cognitive Composite (PACC). Performance was compared with published normative data adjusted for age, sex, and education (National Alzheimer's Coordinating Center; N = 3268). Associations were examined between PACC score, disease duration, and level of disability (assessed using the IBM Functional Rating Scale [IBMFRS]). Results Across all cognitive tests, group performance was within ±1 standard deviation of the normative mean. There was no evidence of associations between PACC score and either disease duration (ρ = -0.04, P = .87) or IBMFRS total score (ρ = 0.14, P = .52). Discussion Memory and executive function in patients with IBM did not differ from normative data, and we observed no evidence of associations between the cognitive composite and disease duration or level of disability. This addresses a question frequently asked by patients and will be of value for clinicians and patients alike.

Objectives: Depression, anxiety, and apathy are the most commonly reported neuropsychiatric symptoms (NPS) in Alzheimer’s disease (AD). Understanding their prevalence in rarer dementias such as frontotemporal dementia (FTD), primary progressive aphasia (PPA), posterior cortical atrophy (PCA), young-onset AD (YOAD), and inherited dementias has implications for both clinical practice and research. In this study, we aimed to examine the current state of knowledge of the prevalence of these three NPS in less prevalent dementias. Design: We conducted a systematic review based on searches of EMBASE, PsycINFO, and PubMed up to September 2019. Results: 47 articles meeting inclusion criteria were identified. Depression, anxiety, and apathy were commonly reported across the phenotypes studied but their prevalence showed large variation between studies. Apathy showed the highest reported frequency in FTD (50–100% across studies), behavioral variant frontotemporal dementia (bvFTD) (73–100%), and YOAD (44–100%). Anxiety was frequently reported in FTD (0–100%) and bvFTD (19–63%). Depression showed the highest prevalence in FTD (7–69%) and YOAD (11–55%). Among the three variants of PPA, sv-PPA is the one most investigated (seven articles). Three or fewer articles were identified examining NPS in the remaining PPA variants, PCA, familial AD, and familial FTD. Inconsistency in the tools used to measure symptoms and small sample sizes were common methodological limitations. Conclusions: Future studies should consider the inclusion of larger sample sizes (e.g. through multicenter collaborations) and the use of harmonized protocols that include the combination of caregiver and patient-derived measures and symptom-specific questionnaires. More research is needed on the phenotype-specific barriers and facilitators for people living with dementia to successfully engage in self-reports of NPS.

ObjectiveTo investigate predictors of performance on a range of cognitive measures including the Preclinical Alzheimer Cognitive Composite (PACC) and test for associations between cognition and dementia biomarkers in Insight 46, a substudy of the Medical Research Council National Survey of Health and Development.MethodsA total of 502 individuals born in the same week in 1946 underwent cognitive assessment at age 69–71 years, including an adapted version of the PACC and a test of nonverbal reasoning. Performance was characterized with respect to sex, childhood cognitive ability, education, and socioeconomic position (SEP). In a subsample of 406 cognitively normal participants, associations were investigated between cognition and β-amyloid (Aβ) positivity (determined from Aβ-PET imaging), whole brain volumes, white matter hyperintensity volumes (WMHV), and APOE ε4.ResultsChildhood cognitive ability was strongly associated with cognitive scores including the PACC more than 60 years later, and there were independent effects of education and SEP. Sex differences were observed on every PACC subtest. In cognitively normal participants, Aβ positivity and WMHV were independently associated with lower PACC scores, and Aβ positivity was associated with poorer nonverbal reasoning. Aβ positivity and WMHV were not associated with sex, childhood cognitive ability, education, or SEP. Normative data for 339 cognitively normal Aβ-negative participants are provided.ConclusionsThis study adds to emerging evidence that subtle cognitive differences associated with Aβ deposition are detectable in older adults, at an age when dementia prevalence is very low. The independent associations of childhood cognitive ability, education, and SEP with cognitive performance at age 70 have implications for interpretation of cognitive data in later life.

Background: Cross-sectional studies in presymptomatic familial Alzheimer’s disease (FAD), have associated binding deficits with preclinical AD. How impairments in visual-short term memory (VSTM) relate to longitudinal change and proximity to expected symptom onset (EYO) is less characterized.Methods: Thirty-two FAD mutation carriers (23 presymptomatic; 9 symptomatic) carrying a mutation in either presenilin 1 or amyloid precursor protein genes and 67 healthy controls were included in an extension VSTM cross-sectional study. Forty-eight participants (23 presymptomatic carriers, 6 symptomatic and 19 healthy controls) who had at least two annual visits (median= 3), were included in the longitudinal study. Participants completed the “What was where?” relational binding task (which measures memory for object identification, localisation and object-location binding under different conditions of memory load and delay), neuropsychology assessments and genetic testing. Results: While cross-sectionally only symptomatic carriers (N=9) showed significant impairments in VSTM performance, longitudinally, presymptomatic carriers within 8.5 years of estimated symptom onset (mean=5.8 years ±SD [1.8], N=11) showed a faster rate of decline in localisation performance in long-delay conditions (4s) compared to controls: increase/year in localisation error was 6.9% greater in the high-memory load condition (p=0.008) and 7.0% greater for the low-memory load condition (p=0.043). Change in this metric preceded presymptomatic changes in traditional measures of verbal episodic memory. Symptomatic carriers had 15% faster reduction in identification performance per year compared to controls (p=0.036) and some evidence of faster increase in localisation error (6.5% increase/year; p=0.066). The earliest significant difference in VSTM performance between FAD mutation carriers (presymptomatic and symptomatic) and controls was in localisation performance, six years prior to estimated symptom onset (p=0.024). Conclusions: This longitudinal study of FAD, suggests changes in VSTM resolution, which measure precision and thus quality of recall of the memory presentation, may be sensitive markers for tracking and predicting cognitive decline in preclinical AD.

Visual short-term memory (VSTM) deficits including VSTM binding have been associated with Alzheimer's disease (AD) from preclinical to dementia stages, cross-sectionally. Yet, longitudinal investigations are lacking. The objective of this study was to evaluate VSTM function longitudinally and in relation to expected symptom onset in a cohort of familial Alzheimer's disease. Ninety-nine individuals (23 presymptomatic; 9 symptomatic and 67 controls) were included in an extension cross-sectional study and a sub-sample of 48 (23 presymptomatic carriers, 6 symptomatic and 19 controls), attending two to five visits with a median interval of 1.3 years, included in the longitudinal study. Participants completed the “What was where?” relational binding task (which measures memory for object identification, localisation and object-location binding under different conditions of memory load and delay), neuropsychology assessments and genetic testing. Compared to controls, presymptomatic carriers within 8.5 years of estimated symptom onset showed a faster rate of decline in localisation performance in long-delay conditions (4s) and in traditional neuropsychology measures of verbal episodic memory. This study represents the first longitudinal VSTM investigation and shows that changes in memory resolution may be sensitive to tracking cognitive decline in preclinical AD at least as early as changes in the more traditional verbal episodic memory tasks., Highlights • VSTM function was investigated in presymptomatic and symptomatic FAD carriers. • PMCs showed faster decline in VSTM function (target localisation) than controls. • Target localisation accuracy decreased with proximity to expected symptom onset. • “What was where?” may be sensitive to tracking preclinical cognitive decline.