Alzheimer's disease (AD) is the most common cause of dementia at older age. Although less prevalent before the age of 65 years, it is still the most frequent cause of early-onset dementia followed by frontotemporal dementia. The typical presentation of AD is memory dysfunction, however, presentations with prominent cognitive impairment in other domains besides memory, like prominent apraxia, language problems, or executive dysfunction, may occur and are relatively more common in early-onset AD. In this retrospective descriptive study, we determined the prevalence of non-memory presentations in a large sample of early-onset AD patients compared to late-onset AD. The clinical files of 270 patients with AD starting before the age of 65 years and 90 patients with late-onset AD ( 65 years) were reviewed to assess clinical characteristics. Patients were classified as memory presentation and non-memory presentation according to their clinical presentation. The mean age of the early-onset group was 56 +/- 5 years and 74 +/- 6 years for the late-onset group. A third of the early-onset AD group presented with non-memory symptoms compared to only 6% in the late-onset group (p < 0.001). Within the group with non-memory presentations, apraxia/visuospatial dysfunction was the most prevalent presenting symptom (12%). Patients with early-onset AD often present with a non-memory phenotype, of which apraxia/visuospatial dysfunction is the most common presenting symptom. Atypical presentations of AD should be considered in the clinical differential diagnosis of early-onset dementia.
ObjectiveTo develop a visual rating scale for posterior atrophy (PA) assessment and to analyse whether this scale aids in the discrimination between Alzheimer’s disease (AD) and other dementias.MethodsMagnetic resonance imaging of 118 memory clinic patients were analysed for PA (range 0–3), medial temporal lobe atrophy (MTA) (range 0–4) and global cortical atrophy (range 0–3) by different raters. Weighted-kappas were calculated for inter- and intra-rater agreement. Relationships between PA and MTA with the MMSE and age were estimated with linear-regression analysis.ResultsIntra-rater agreement ranged between 0.93 and 0.95 and inter-rater agreement between 0.65 and 0.84. Mean PA scores were higher in AD compared to controls (1.6 ± 0.9 and 0.6 ± 0.7, p < 0.01), and other dementias (0.8 ± 0.8, p < 0.01). PA was not associated with age compared to MTA (B = 1.1 (0.8) versus B = 3.1 (0.7), p < 0.01)). PA and MTA were independently negatively associated with the MMSE (B = −1.6 (0.5), p < 0.01 versus B = −1.4 (0.5), p < 0.01).ConclusionThis robust and reproducible scale for PA assessment conveys independent information in a clinical setting and may be useful in the discrimination of AD from other dementias.
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.
Background/Aims: Our objective was to compare the mortality risks of patients with early- and late-onset dementia with non-demented controls of the same age range and to analyse the mortality risks in subtypes of dementia. Methods: We included 1,203 subjects from our memory clinic. Patients with dementia were subdivided into 2 groups, with early- (<65 years) or late-onset dementia (≧65 years), and compared with non-demented controls of the same age range. We used Cox proportional hazard models to estimate mortality risks. Results: When compared to non-demented controls of the same age range, the patients with early-onset dementia had a strongly elevated mortality risk [hazard ratio (95% confidence interval) = 43.3 (3.1–600.4)], while those with late-onset dementia had a moderately increased mortality risk compared to older controls [hazard ratio (95% confidence interval) = 3.4 (1.8–6.2)]. An additional analysis showed that, adjusted for age, Alzheimer’s disease seemed to have the most benign course, with a fourfold increased mortality risk. Dementia with Lewy bodies and vascular dementia (frequently seen at older age) and frontotemporal lobar degeneration and ‘other dementias’ (often found at younger age) had a six- to eightfold increased mortality risk. Conclusion: Dementia is a risk factor for death. Especially in young patients the impact of dementia on mortality is high.
We show cognitive trajectories of different types of dementia. These estimations of natural disease course have important value for the design of clinical trials as neuropsychological measures are increasingly being used as outcome measures.
Medial temporal lobe atrophy (MTA) is a recognized marker of Alzheimer's disease (AD), however, it can be prominent in frontotemporal lobar degeneration (FTLD). There is an increasing awareness that posterior atrophy (PA) is important in AD and may aid the differentiation of AD from FTLD. Visual rating scales are a convenient way of assessing atrophy in a clinical setting. In this study, 2 visual rating scales measuring MTA and PA were used to compare atrophy patterns in 62 pathologically-confirmed AD and 40 FTLD patients. Anatomical correspondence of MTA and PA was assessed using manually-delineated regions of the hippocampus and posterior cingulate gyrus, respectively. Both MTA and PA scales showed good inter- and intrarater reliabilities (kappa > 0.8). MTA scores showed a good correspondence with manual hippocampal volumes. Thirty percent of the AD patients showed PA in the absence of MTA. Adding the PA to the MTA scale improved discrimination of AD from FTLD, and early-onset AD from normal aging. These results underline the importance of considering PA in AD diagnosis, particularly in younger patients where medial temporal atrophy may be less conspicuous.
Patients with early onset AD show more rapid cognitive decline than patients with late onset, suggesting that early onset AD follows a more aggressive course. Furthermore, this effect seems to be most prominent in patients with early onset who do not carry the genetic APOE epsilon4 risk factor for AD.
Background and Purpose-We sought to determine the predictive value of magnetic resonance imaging measures of vascular disease (white matter hyperintensities [WMHs], lacunes, microbleeds, and infarcts) compared with atrophy on the progression of mild cognitive impairment to dementia. Methods-We included 152 consecutive patients with mild cognitive impairment. Baseline magnetic resonance imaging was used to determine the presence of medial temporal lobe atrophy and vascular disease (presence of lacunes, microbleeds, and infarcts was determined, and WMHs were rated on a semiquantitative scale). Patients were followed up for 2Ϯ1 years. Results-Seventy-two (47%) patients progressed to dementia during follow-up. Of these, 56 (37%) patients were diagnosed with Alzheimer's disease, and 16 (10%) patients were diagnosed with a non-Alzheimer dementia (including vascular dementia, frontotemporal lobar degeneration, and Parkinson dementia). Converters were older and had a lower Mini-Mental State Examination score at baseline. On baseline magnetic resonance imaging, patients who progressed to a non-Alzheimer dementia showed more severe WMHs and had a higher prevalence of lacunes in the basal ganglia and microbleeds compared with nonconverters. Cox proportional-hazard models showed that, adjusted for age and sex, baseline medial temporal lobe atrophy (hazard ratioϭ2.9; 95% CI, 1.7 to 5.3), but not vascular disease, was associated with progression to Alzheimer's disease. By contrast, deep WMHs (hazard ratioϭ5.7; 95% CI, 1.2 to 26.7) and periventricular hyperintensities (hazard ratioϭ6.5; 95% CI, 1.4 to 29.8) predicted progression to non-Alzheimer dementia. Furthermore, microbleeds (hazard ratioϭ2.6; 95% CI, 0.9 to 7.5) yielded a Ͼ2-fold increased, though nonsignificant, risk of non-Alzheimer dementia. Conclusion-Medial
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