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We aimed to investigate associations between regional cortical thickness and rate of decline over time in 4 cognitive domains in patients with subjective cognitive decline (SCD). We included 233 SCD patients with the total number of 654 neuropsychological assessments (median = 3, range = 2–8) and available baseline magnetic resonance imaging from the Amsterdam Dementia Cohort (125 males, age: 63 ± 9, Mini–Mental State Examination score: 28 ± 2). We assessed longitudinal cognitive functioning at baseline and follow-up in 4 cognitive domains (composite Z-scores): memory, attention, executive function, and language. Thickness (millimeter) was estimated using FreeSurfer for frontal, temporal, parietal, cingulate, and occipital cortices. We used linear mixed models to estimate effects of cortical thickness on cognitive performance (dependent variables). There were no associations between cortical thickness and baseline cognition, but a faster subsequent rate of memory loss was associated with thinner cortex of the frontal [β (SE) = 0.20 (0.07)], temporal [β (SE) = 0.18 (0.07)], and occipital [β (SE) = 0.22 (0.09)] cortices (all p < 0.05FDR). These findings illustrate that early cortical changes, particularly in the temporal cortex, herald incipient cognitive decline related to neurodegenerative diseases, most prominently Alzheimer's disease.

BACKGROUND: Many older people worry about cognitive decline. Early cognitive screening in an anonymous and easily accessible manner may reassure older people who are unnecessarily worried about normal cognitive aging while it may also expedite help seeking in case of suspicious cognitive decline.OBJECTIVE: To develop and validate online and telephone-based automated self-tests of cognitive function.METHODS: We examined the feasibility and validity of the self-tests in a prospective study of 117 participants of whom 34 had subjective cognitive decline (SCD), 30 had mild cognitive impairment (MCI), and 53 had dementia. The ability of these self-tests to accurately distinguish MCI and dementia from SCD was examined with ROC curves. Convergent validity was examined by calculating rank correlations between the self-tests and neuropsychological tests.RESULTS: Both the online and telephone cognitive self-tests were feasible, because the majority of participants (86% and 80%, respectively) were able to complete them. The online self-test had adequate diagnostic accuracy in the screening for MCI and dementia versus SCD with an Area under the Curve (AUC) of 0.86 (95% CI: 0.78-0.93). The AUC of the MMSE was 0.82 (95% CI: 0.74-0.89). By contrast, the telephone self-test had lower diagnostic accuracy (AUC = 0.75, 95% CI: 0.64-0.86). Both self-tests had good convergent validity as demonstrated by moderate to strong rank correlations with neuropsychological tests.CONCLUSION: We demonstrated good diagnostic accuracy and convergent validity for the online self-test of cognitive function. It is therefore a promising tool in the screening for MCI and dementia.

ObjectiveTo examine cross-sectional effects of cognitive reserve (CR) and brain reserve (BR) on cognition across the spectrum of Alzheimer disease (AD).MethodsWe included 663 AD biomarker–positive participants with dementia (probable AD, n = 462) or in the predementia stages (preclinical/prodromal AD, n = 201). Education was used as a proxy of CR and intracranial volume as a proxy of BR. Cognition was assessed across 5 domains (memory, attention, language, visuospatial, and executive functions). We performed multiple linear regression models to examine effects of CR and BR on cognitive domain Z scores, adjusted for cerebral atrophy. Furthermore, we assessed differences in effects according to disease stage and across degrees of total reserve using a 4-level variable (high CR/high BR, high CR/low BR, low CR/high BR, and low CR/low BR).ResultsWe found positive, independent effects of both CR and BR across multiple cognitive domains. Stratification for disease stage showed that effects of CR on attention and executive functioning were greater in predementia than in dementia (β = 0.39 vs β = 0.21 [Welch t = 2.40, p < 0.01] and β = 0.46 vs β = 0.26 [t = 2.83, p < 0.01]). Furthermore, we found a linear trend for better cognitive performance in all domains in the high CR/high BR group, followed by high CR/low BR, low CR/high BR, and then low CR/low BR (p for trend ConclusionsCR and BR both independently mitigate cognitive symptoms in AD. The positive effect of CR is most strongly expressed in the predementia stages and the additive effects of high CR and BR are most beneficial.

Background Survival after dementia diagnosis varies considerably. Previous studies were focused mainly on factors related to demographics and comorbidity rather than on Alzheimer’s disease (AD)-related determinants. We set out to answer the question whether markers with proven diagnostic value also have prognostic value. We aimed to identify disease-related determinants associated with mortality in patients with AD. Methods We included 616 patients (50% female; age 67 ± 8 years; mean Mini Mental State Examination score 22 ± 3) with dementia due to AD from the Amsterdam Dementia Cohort. Information on mortality was obtained from the Dutch Municipal Register. We used age- and sex-adjusted Cox proportional hazards analysis to study associations of baseline demographics, comorbidity, neuropsychology, magnetic resonance imaging (MRI) (medial temporal lobe, global cortical and parietal atrophy, and measures of small vessel disease), and cerebrospinal fluid (CSF) (β-amyloid 1–42, total tau, and tau phosphorylated at threonine 181 [p-tau]) with mortality (outcome). In addition, we built a multivariate model using forward selection. Results After an average of 4.9 ± 2.0 years, 213 (35%) patients had died. Age- and sex-adjusted Cox models showed that older age (HR 1.29 [95% CI 1.12–1.48]), male sex (HR 1.60 [95% CI 1.22–2.11]), worse scores on cognitive functioning (HR 1.14 [95% CI 1.01-1.30] to 1.31 [95% CI 1.13–1.52]), and more global and hippocampal atrophy on MRI (HR 1.18 [95% CI 1.01-1.37] and HR 1.18 [95% CI 1.02-1.37]) were associated with increased risk of mortality. There were no associations with comorbidity, level of activities of daily living, apolipoprotein E (APOE) ε4 status, or duration of disease. Using forward selection, the multivariate model included a panel of age, sex, cognitive tests, atrophy of the medial temporal lobe, and CSF p-tau. Conclusions In this relatively young sample of patients with AD, disease-related determinants were associated with an increased risk of mortality, whereas neither comorbidity nor APOE genotype had any prognostic value. Electronic supplementary material The online version of this article (10.1186/s13195-018-0348-0) contains supplementary material, which is available to authorized users.

When differential diagnosis of dementia includes both Alzheimer's disease (AD) and the behavioural variant of frontotemporal dementia (bvFTD), distribution of cerebral glucose metabolism as measured using [18F]‑2‑fluoro‑2‑deoxy‑d‑glucose positron emission tomography ([18F]FDG-PET) may be helpful. One important clue for differentiation is the presence of hypometabolism in the posterior cingulate cortex (PCC), usually associated with AD. PCC hypometabolism however, could also be present in bvFTD. Therefore, the specificity of PCC hypometabolism was examined. Based on visual reading PCC hypometabolism was present in 69–73/81 probable AD patients, in 10–16/33 probable bvFTD patients, and in 0–1/22 cognitive normal (CN) subjects. Findings were validated using a PCC to reference tissue [18F]FDG standard uptake value ratio (SUVr) cut-off, which was derived from the receiver operating characteristic (ROC) separating probable AD from CN, resulting in 9–14/33 bvFTD patients having PCC hypometabolism, depending on the reference tissue used. In conclusion, PCC hypometabolism is not restricted to AD. Keywords: Alzheimer's disease, Frontotemporal dementia, Posterior cingulate cortex, [18F]FDG-PET, Hypometabolism

Introduction We examined the association between decreased cerebral blood flow (CBF) and cognitive impairment in Alzheimer's disease (AD), mild cognitive impairment (MCI), and subjective cognitive decline (SCD). Methods We included 161 AD, 95 MCI, and 143 SCD patients from the Amsterdam Dementia Cohort. We used 3-T pseudo-continuous arterial spin labeling to estimate whole-brain and regional partial volume–corrected CBF. Neuropsychological tests covered global cognition and five cognitive domains. Associations were investigated using linear regression analyses. Results In the whole sample, reduced overall and regional CBF was associated with impairment in all cognitive domains. We found significant interactions between diagnosis and CBF for language and between diagnosis and parietal CBF for global cognition and executive functioning. Stratification showed that decreased CBF was associated with worse performance in AD patients but not in MCI or SCD. Discussion Our results suggest that CBF may have potential as a functional marker of disease severity.

Few data are available concerning the role of risk markers for Alzheimer's disease (AD) in progression to AD dementia among subjects with mild cognitive impairment (MCI). We therefore investigated the role of well-known AD-associated single-nucleotide polymorphism (SNP) in the progression from MCI to AD dementia. Four independent MCI data sets were included in the analysis: (a) the German study on Aging, Cognition and Dementia in primary care patients (n=853); (b) the German Dementia Competence Network (n=812); (c) the Fundació ACE from Barcelona, Spain (n=1245); and (d) the MCI data set of the Amsterdam Dementia Cohort (n=306). The effects of single markers and combined polygenic scores were measured using Cox proportional hazards models and meta-analyses. The clusterin (CLU) locus was an independent genetic risk factor for MCI to AD progression (CLU rs9331888: hazard ratio (HR)=1.187 (1.054-1.32); P=0.0035). A polygenic score (PGS1) comprising nine established genome-wide AD risk loci predicted a small effect on the risk of MCI to AD progression in APOE-ϵ4 (apolipoprotein E-ϵ4) carriers (HR=1.746 (1.029-2.965); P=0.038). The novel AD loci reported by the International Genomics of Alzheimer's Project were not implicated in MCI to AD dementia progression. SNP-based polygenic risk scores comprising currently available AD genetic markers did not predict MCI to AD progression. We conclude that SNPs in CLU are potential markers for MCI to AD progression.

The relation between pathology and cognitive dysfunction in dementia is still poorly understood, although disturbed communication between different brain regions is almost certainly involved. In this study we combine magneto-encephalography (MEG) and network analysis to investigate the role of functional sub-networks (modules) in the brain with regard to cognitive failure in Alzheimer's disease. Whole-head resting-state (MEG) was performed in 18 Alzheimer patients (age 67 ± 9, 6 females, MMSE 23 ± 5) and 18 healthy controls (age 66 ± 9, 11 females, MMSE 29 ± 1). We constructed functional brain networks based on interregional synchronization measurements, and performed graph theoretical analysis with a focus on modular organization. The overall modular strength and the number of modules changed significantly in Alzheimer patients. The parietal cortex was the most highly connected network area, but showed the strongest intramodular losses. Nonetheless, weakening of intermodular connectivity was even more outspoken, and more strongly related to cognitive impairment. The results of this study demonstrate that particularly the loss of communication between different functional brain regions reflects cognitive decline in Alzheimer's disease. These findings imply the relevance of regarding dementia as a functional network disorder.

Objective: Our purpose was to investigate associations between different cognitive profiles and their underlying functional brain changes as measured by electroencephalogram (EEG) in Alzheimer’s disease (AD). Methods: EEG was obtained and neuropsychological performance assessed in 254 patients with AD. The EEGs were visually assessed for the presence of focal and/or diffuse abnormalities. Multivariate analysis of variance for repeated measures was performed with presence of focal and/or diffuse abnormalities as between-subjects factor and neuropsychological tests as within-subject factor. Age, sex and education were entered as covariates. Results: Twenty-eight percent of the patients had a normal EEG, 32% had focal abnormalities, 14% diffuse abnormalities and 26% had both focal and diffuse abnormalities. Patients with a normal EEG presented with a cognitive profile in which memory was mostly impaired. Patients with focal and diffuse EEG abnormalities presented with a nonmemory profile. Conclusion: These results illustrate that specific types of EEG abnormalities are associated with different cognitive profiles in AD, providing biological support in terms of brain functioning for variability in cognitive impairment.

De ziekte van Alzheimer (ad) is een neurodegeneratieve aandoening waarvan de prevalentie sterk samenhangt met leeftijd. De prevalentie neemt toe van 7% bij mensen van 65 jaar tot 25% bij mensen ouder dan 80 jaar (Forstl, 1998; Ott et al., 1998). In Nederland wordt het aantal patienten met ad momenteel geschat op ruim 190.000 met een incidentie van 4.000 per jaar. Gezien de dubbele vergrijzing zal dit aantal snel toenemen tot naar schatting meer dan 412.000 patienten in 2050 (Health Council of the Netherlands, 2002).

Background and Purpose— In patients with subjective cognitive decline, we assessed whether small vessel disease was associated with clinical progression and cognitive decline. Methods— We included 334 patients with subjective cognitive decline. Follow-up was 3±2 years. Results— Fifty-three (16%) patients progressed clinically to mild cognitive impairment or dementia. White matter hyperintensities were associated with clinical progression and with annual decline on memory, attention, executive functioning, and global cognition. Microbleeds and lacunes were not associated with clinical progression or cognitive decline. Conclusions— In patients with subjective cognitive decline, patients with white matter hyperintensities are at increased risk of clinical progression and cognitive decline.

Objective Alzheimer's disease (AD) is a heterogeneous disorder with complex underlying neuropathology that is still not completely understood. For better understanding of this heterogeneity, we aimed to identify cognitive subtypes using latent class analysis (LCA) in a large sample of patients with AD dementia. In addition, we explored the relationship between the identified cognitive subtypes, and their demographical and neurobiological characteristics.Methods We performed LCA based on neuropsychological test results of 938 consecutive probable patients with AD dementia using Mini-Mental State Examination as the covariate. Subsequently, we performed multinomial logistic regression analysis with cluster membership as dependent variable and dichotomised demographics, APOE genotype, cerebrospinal fluid biomarkers and MRI characteristics as independent variables.Results LCA revealed eight clusters characterised by distinct cognitive profile and disease severity. Memory-impaired clusters—mild-memory (MILD-MEM) and moderate-memory (MOD-MEM)—included 43% of patients. Memory-spared clusters mild-visuospatial-language (MILD-VILA), mild-executive (MILD-EXE) and moderate-visuospatial (MOD-VISP) —included 29% of patients. Memory-indifferent clusters mild-diffuse (MILD-DIFF), moderate-language (MOD-LAN) and severe-diffuse (SEV-DIFF) —included 28% of patients. Cognitive clusters were associated with distinct demographical and neurobiological characteristics. In particular, the memory-spared MOD-VISP cluster was associated with younger age, APOE e4 negative genotype and prominent atrophy of the posterior cortex.Conclusions Using LCA, we identified eight distinct cognitive subtypes in a large sample of patients with AD dementia. Cognitive clusters were associated with distinct demographical and neurobiological characteristics.

Early-onset Alzheimer's disease (AD) patients present a different clinical profile than late-onset AD patients. This can be partially explained by cortical atrophy, although brain organization might provide more insight. The aim of this study was to examine functional connectivity in early-onset and late-onset AD patients. Resting-state fMRI scans of 20 early-onset ( = 65 years old) AD patients and 15 "young'' ( = 65 years old) age-matched controls were available. Resting-state network-masks were used to create subject-specific maps. Group differences were examined using a non-parametric permutation test, accounting for gray-matter. Performance on five cognitive domains were used in a correlation analysis with functional connectivity in AD patients. Functional connectivity was not different in any of the RSNs when comparing the two control groups (young vs. old controls), which implies that there is no general effect of aging on functional connectivity. Functional connectivity in early-onset AD was lower in all networks compared to age-matched controls, where late-onset AD showed lower functional connectivity in the default-mode network. Functional connectivity was lower in early-onset compared to late-onset AD in auditory-, sensory-motor, dorsal-visual systems and the default mode network. Across patients, an association of functional connectivity of the default mode network was found with visuoconstruction. Functional connectivity of the right dorsal visual system was associated with attention across patients. In late-onset AD patients alone, higher functional connectivity of the sensory-motor system was associated with poorer memory performance. Functional brain organization was more widely disrupted in early-onset AD when compared to late-onset AD. This could possibly explain different clinical profiles, although more research into the relationship of functional connectivity and cognitive performance is needed

Objective: We assessed whether preclinical Alzheimer disease (AD) based on CSF biomarkers at baseline predicts decline in cognitive functioning as measured by repeated neuropsychological tests for 4 cognitive domains in patients with subjective complaints. Methods: We included 132 patients with subjective complaints from our memory clinic-based Amsterdam Dementia Cohort, who underwent lumbar puncture and had repeated (range 2-7) neuropsychological evaluations. Follow-up was 2 +/- 1 years. CSF biomarkers amyloid-beta (A beta 42), total tau (Tau), and hyperphosphorylated tau-181 were used to define National Institute on Aging-Alzheimer's Association (NIA-AA) preclinical AD stages. Predictive value of preclinical AD stages as defined by CSF biomarkers, individual biomarkers, and A beta 42/tau ratio was assessed using linear mixed models. Outcome measures were compound z scores for memory, attention, executive functioning, language, and global cognition. Analyses were adjusted for age, sex, and education. Results: Patients were 61 +/- 8 years old; 56 (42%) were women. Average baseline Mini-Mental State Examination score was 28.3 +/- 1.5. Patients who fulfilled criteria for preclinical AD (stage 1: n = 11 + stage 2: n = 10) showed decline over time in memory (beta +/- SE -0.41 +/- 0.14, p

Background Visual hallucinations (VH) in Parkinson's disease (PD) are associated with PD dementia and have been related to cognitive impairments in non-demented PD patients. Reports on the specific cognitive domains affected are conflicting. The aim of the present study was to investigate the presence of specific cognitive impairments in non-demented PD patients with VH, compared to those without VH. Methods We compared the clinical characteristics and neuropsychological test scores of 31 non-demented PD patients with VH with those of 31 PD patients without VH that were carefully matched for sex, age, disease duration and educational level. Several non-motor symptoms, including depression, anxiety and sleep disturbances, were also taken into account, as these may influence cognitive performance. Results The PD with VH group performed significantly worse on the Trail Making Test part A ( p = 0.01) and the Rey Auditory Verbal Learning Test, immediate recall ( p = 0.01). In addition, PD patients with VH were more anxious, more depressed and reported more sleep disturbances. Verbal learning scores were not associated with levels of anxiety, depression or sleep disruption, whereas worse Trail Making Test A performance was associated with concomitant sleep disturbances. Conclusions In non-demented PD patients, the presence of VH is associated with a cognitive profile characterized by impairments in verbal learning and probably attention. Since these cognitive functions are believed to be non-dopaminergic mediated functions, the present results support the hypothesis that multiple neurotransmitter systems, other than dopamine, contribute to the pathophysiology of VH in PD.

Disproportionate medial temporal lobe atrophy (MTA) is an early finding in Alzheimer's disease (AD). Episodic memory impairment in AD is associated with the degree of MTA. Episodic memory impairment and MTA are also found in semantic dementia (SD) and in right temporal lobe atrophy (RTLA), the temporal variants of frontotemporal dementia, but their relationship is unclear.To compare episodic memory impairment among patients with these temporal variants of frontotemporal dementia with that of patients with AD with the same degree of MTA.Episodic memory was tested with the visual association test, and semantic memory (SM) with animal fluency and the visual association naming test. MTA was measured using a visual rating scale. Each patient with SD or RTLA was matched for MTA with two patients with AD. Comparisons of episodic memory and SM were made for patients with SD versus matched patients with AD; patients with RTLA versus matched patients with AD and for SD, RTLA and all patients with AD.27 patients with SD and 11 with RTLA were matched with 54 and 22 patients with AD, respectively. Episodic memory was less impaired in patients with SD than in those with AD (8 versus 2; p0.001) and in patients with RTLA than in those with AD (10 versus 4.5; p=0.009). Semantic memory was more affected in patients with SD than in those with AD, and the Mini Mental State Examination score was higher in patients with RTLA than in those with AD. Comparison of the three diagnostic groups showed that episodic memory was most impaired in AD, whereas SM was most impaired in SD.Since episodic memory impairment is more severe in AD than in SD and RTLA, despite a comparable degree of MTA, atrophy of the medial temporal lobe alone cannot account for episodic memory dysfunction.

Alzheimer's disease (AD) in younger patients is associated with a higher prevalence of atypical symptoms. We examined neuropsychological performance according to age-at-onset. We assessed cognition in 172 patients with AD (81 early and 91 late onset) in five cognitive domains (memory, language, visuo-spatial functioning, executive functioning, attention). Dementia severity was assessed using the Mini-Mental State Examination (MMSE) and global cognitive decline using Cambridge Cognitive Examination (CAMCOG). Analyses of variance were performed with age-at-onset as between-subjects factor, and gender and education as covariates. Analysis was repeated after stratification for dementia severity (based on median MMSE). In early onset AD, age (mean ± SD) was 60 ± 4 years; 44 (54%) were female. In late onset AD, age was 72 ± 5 years; 47 (52%) were female. Dementia severity and global cognitive decline did not differ between groups (early onset: MMSE: 20 ± 5, CAMCOG: 69 ± 15, late onset: MMSE: 21 ± 5, CAMCOG: 70 ± 15; p > 0.05). Early onset patients performed worse than late onset patients on visuo-spatial functioning (p < 0.01), executive functioning (p < 0.001), and attention (p < 0.01). Late onset patients performed worse on memory, although not significantly (p = 0.11). Stratification for dementia severity showed that in mildly demented early onset patients, memory function was remarkably preserved compared to late onset patients (p < 0.01). In moderate AD, differences in memory function disappeared, but early onset patients performed worse on visuo-spatial functioning (p < 0.01), executive functioning (p < 0.001), and attention (p < 0.01) than late onset patients. Adjustment for APOE left results unchanged. In conclusion, early onset AD presents with a different cognitive profile and the disease course seems different. Relative sparing of memory function in early stages stresses the need to adequately test other cognitive domains.

Total sleep deprivation in healthy subjects has a profound effect on the performance on tasks measuring sustained attention or vigilance. We here report how a selective disruption of deep sleep only, that is, selective slow-wave activity (SWA) reduction, affects the performance of healthy well-sleeping subjects on several tasks: a "simple" and a "complex" vigilance task, a declarative learning task, and an implicit learning task despite unchanged duration of sleep. We used automated electroencephalogram (EEG) dependent acoustic feedback aimed at selective interference with-and reduction of-SWA. In a within-subject repeated measures crossover design, performance on the tasks was assessed in 13 elderly adults without sleep complaints after either SWA-reduction or after normal sleep. The number of vigilance lapses increased as a result of SWA reduction, irrespective of the type of vigilance task. Recognition on the declarative memory task was also affected by SWA reduction, associated with a decreased activation of the right hippocampus on encoding (measured with fMRI) suggesting a weaker memory trace. SWA reduction, however, did not affect reaction time on either of the vigilance tasks or implicit memory task performance. These findings suggest a specific role of slow oscillations in the subsequent daytime ability to maintain sustained attention and to encode novel declarative information but not to maintain response speed or to build implicit memories. Of particular interest is that selective SWA reduction can mimic some of the effects of total sleep deprivation, while not affecting sleep duration.

Aim: We examined whether impairment in specific cognitive domains in Alzheimer’s disease (AD) differed according to APOE genotype and age at onset. Methods: Cognitive functions of 229 consecutive AD patients were assessed using Visual Association Test (VAT), Memory Impairment Screen+ (MIS+), VAT object naming, fluency test and Trail Making Test (TMT). Dementia severity was assessed using MMSE. ANOVAs were performed with APOE genotype and age at onset as independent variables and sex, education and MMSE as covariates. Results: 28% of patients were APOE Ε4-negative, 58% heterozygous and 14% homozygous. A significant association between APOE genotype and VAT and MIS+ was found when correcting for sex and education. An interaction effect between APOE genotype and age at onset on VAT and VAT object naming was found, with young carriers performing worse than young noncarriers. By contrast, when additionally correcting for MMSE, a significant association between APOE genotype and VAT object naming, TMT-A and TMT-B was found, with noncarriers performing worse than carriers. Conclusion: Memory was more impaired among APOE Ε4 carriers than among noncarriers. By contrast, naming, executive functions and mental speed were more impaired among APOE Ε4 noncarriers. This suggests that the APOE genotype modifies the clinical phenotype in terms of cognitive impairment in AD.

BackgroundIn Alzheimer's disease (AD), some patients present with cognitive impairment other than episodic memory disturbances. We evaluated whether occurrence of posterior atrophy (PA) and medial temporal lobe atrophy (MTA) could account for differences in cognitive domains affected.MethodsIn 329 patients with AD, we assessed five cognitive domains: memory, language, visuospatial functioning, executive functioning, and attention. Magnetic resonance imaging (MRI) was rated visually for the presence of MTA and PA. Two-way analyses of variance were performed with MTA and PA as independent variables, and cognitive domains as dependent variables. Gender, age, and education were covariates. As PA is often encountered in younger patients, analyses were repeated after stratification for age of onset (early onset, ≤ 65 years).ResultsThe mean age of the participants was 67 years, 175 (53%) were female, and the mean Mini-Mental State Examination (score ± standard deviation) was 20 ± 5 points. Based on dichotomized magnetic resonance imaging ratings, 84 patients (26%) had MTA and PA, 98 (30%) had MTA, 57 (17%) had PA, and 90 (27%) had neither. MTA was associated with worse performance on memory, language, and attention (all, P