New insights into atypical Alzheimer's disease in the era of biomarkers

Graff‐Radford, Jonathan; Yong, Keir X. X.; Apostolova, Liana G.; Bouwman, Femke H.; Carrillo, María C.; Dickerson, Bradford C.; Rabinovici, Gil D.; Schott, Jonathan M.; Jones, David T.; Murray, Melissa E.

doi:10.1016/s1474-4422(20)30440-3

Cited by 307 publications

(343 citation statements)

References 100 publications

(144 reference statements)

Supporting

Mentioning

284

Contrasting

Unclassified

Order By: Relevance

“…A possible explanation could be found in our exploration in Alzheimer's disease phenotypes, in which only amnestic Alzheimer's disease donors showed an association between NbM MRI volume and p-tau. As this association was made with a very small sample size, this should be futher explored in a larger cohort with a variety of phenotypes 1,41 .…”

Section: Discussionmentioning

confidence: 99%

“…Clinically, a distinction can be made between an amnestic and non-amnestic subtype. In amnestic Alzheimer’s disease, memory deficits are among the first symptoms, and in non-amnestic Alzheimer’s disease, memory is initially spared, but symptoms of visuospatial impairment, aphasia, or behavioural/dysexecutive dysfunction are more prominent 1 . Pathologically, Alzheimer’s disease is characterized by abnormal aggregation of amyloid-beta (Aβ) forming amyloid plaques, and phosphorylated-tau (p-tau) forming neurofibrillary tangles (NFT) 2,3 .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Structural (dys)connectivity associates with cholinergic cell density of the nucleus basalis of Meynert in Alzheimer’s disease

Lin

Frigerio

Boon

et al. 2021

Preprint

View full text Add to dashboard Cite

Cognitive deficits in Alzheimer's disease, specifically amnestic (memory dominant) deficits, are associated with cholinergic degeneration in the basal forebrain. The cholinergic nucleus within the basal forebrain, the nucleus basalis of Meynert, exhibits local atrophy and reduced cortical tract integrity on MRI, and reveals amyloid-β and phosphorylated-tau pathology at autopsy. To better understand the pathophysiology of nucleus basalis of Meynert atrophy and its neocortical projections in Alzheimer's disease, we utilized a combined post-mortem in-situ MRI and histopathology approach. A total of 19 Alzheimer's disease (10 amnestic and 9 non-amnestic) and 9 non-neurological control donors underwent 3T T1-weighted MRI for anatomical delineation and volume assessment of the nucleus basalis of Meynert, and diffusion-weighted imaging for microstructural assessment of the nucleus and its projections. At subsequent brain autopsy, tissue dissection and immunohistochemistry were performed for amyloid-β, phosphorylated-tau and choline acetyltransferase. Compared to controls, we observed an MRI-derived volume reduction and altered microstructural integrity of the nucleus basalis of Meynert in Alzheimer's disease donors. Furthermore, decreased cholinergic cell density was associated with reduced integrity of the nucleus and its tracts to the temporal lobe, specifically to the temporal pole of the superior temporal gyrus, and the parahippocampal gyrus. The association between cholinergic cell density and alteration to cortical tracts was specific for amnestic, compared to non-amnestic Alzheimer's disease donors. Our study illustrates that the nucleus basalis of Meynert is severely affected in amnestic Alzheimer's disease, both in terms of pathology within the nucleus, but also in terms of damage to its cortical projections, specifically to the temporal lobe, which may contribute to the observed cognitive deterioration.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Structural (dys)connectivity associates with cholinergic cell density of the nucleus basalis of Meynert in Alzheimer’s disease

Lin

Frigerio

Boon

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…Table-S5[19][20][21][22][23][24][25] ). Compared to bvFTD, bvAD patients less frequently showed compulsive behaviors (45.0%vs68.5%, χ 2 =22.5, p<0.001) and hyperorality (35.9%vs64.1%, χ2 …”

mentioning

confidence: 93%

Provisional research criteria for the behavioral variant of Alzheimer’s disease A systematic review and meta-analysis

Ossenkoppele

Singleton

Groot

et al. 2021

Preprint

View full text Add to dashboard Cite

Importance: The behavioral variant of Alzheimer disease (bvAD) is characterized by early and predominant behavioral deficits caused by AD pathology. This AD phenotype is insufficiently understood and lacks standardized clinical criteria, limiting reliability and reproducibility of diagnosis and scientific reporting. Objective: To perform a systematic review and meta-analysis of the bvAD literature, and use the outcomes to propose provisional research criteria for this syndrome. Data sources: A systematic literature search in PubMed/Medline and Web-of-Science databases (from inception through April 7th, 2021, performed in duplicate) led to the assessment of 83 studies, including 13 suitable for meta-analysis. Study selection: Studies reporting on behavioral, neuropsychological or neuroimaging features in bvAD, and, when available, providing comparisons with typical amnestic-predominant AD (tAD) or behavorial variant frontotemporal dementia (bvFTD). Data extraction and synthesis: We performed random-effects meta-analyses on group-level study results of clinical data, and systematically reviewed the neuroimaging literature. Main outcome and measures: Behavioral symptoms (neuropsychiatric symptoms and bvFTD core clinical criteria), cognitive function (global cognition, episodic memory and executive functioning) and neuroimaging features (structural MRI, [18F]FDG-PET, perfusion SPECT, amyloid-PET and tau-PET). Results: Data were collected for 591 patients with bvAD. There was moderate-to-substantial heterogeneity and moderate risk of bias across studies. bvAD showed more severe behavioral symptoms compared to tAD (standardized mean difference [SMD, 95% confidence interval]: 1.16[0.74-1.59], p<0.001), and a trend towards less severe behavioral symptoms compared to bvFTD (SMD:-0.22[-0.47-0.04], p=0.10). Meta-analyses of cognitive data indicated worse executive performance in bvAD versus tAD (SMD:-1.03[-1.74--0.32], p<0.01), but not compared to bvFTD (SMD:-0.61[-1.75-0.53], p=0.29). bvAD showed a trend towards worse memory performance compared to bvFTD (SMD:-1.31[-2.75-0.14], p=0.08), but did not differ from tAD (SMD:0.43[-0.46-1.33], p=0.34). The neuroimaging literature revealed two distinct bvAD neuroimaging-phenotypes: an AD-like posterior-predominant pattern and a bvFTD-like anterior-predominant pattern, with the former being more prevalent. Conclusions and relevance: Our data indicate that bvAD is clinically most similar to bvFTD, while it shares most pathophysiological features with tAD. Based on these insights, we propose provisional research criteria for bvAD aimed at improving the consistency and reliability of future research and aiding the clinical assessment of this AD phenotype.

show abstract

“…Posterior cortical atrophy is a rare degenerative condition which commonly occurs between ages 50 and 65 and is characterized mainly by visuospatial dysfunction 1 , 2 . This condition is under-recognized and underdiagnosed 1 – 3 because a diagnosis of posterior cortical atrophy is sometimes challenging among assessments of neurodegenerative conditions 3 , in particular, of the mild form and can be delayed not only because of the rarity of this condition but also because, aside from visuospatial dysfunction, patients with mild posterior cortical atrophy function almost normally with respect to memory, language, and behavior and maintain a relatively preserved motivation and insight 3 – 7 . In addition, typical simple neuropsychological tests, e.g., Mini-Mental State Examination (MMSE) 8 , do not focus on symptoms of this condition; rather, their goal is mainly to assess orientation, calculation, repetition, and memory functions.…”

Section: Introductionmentioning

confidence: 99%

Visuospatial working memory dysfunction from tapping span test as a diagnostic tool for patients with mild posterior cortical atrophy

Funayama

Takata

Nakagawa

et al. 2021

Sci Rep

View full text Add to dashboard Cite

Posterior cortical atrophy is a rare degenerative condition with prominent visuospatial dysfunction which commonly occurs between ages 50 and 65. A diagnosis of mild posterior cortical atrophy sometimes challenging and can be delayed because there are currently no established neuropsychological examination methods that can easily be used in clinical settings. In this study, we examined whether the tapping span test is a potential diagnostic tool for posterior cortical atrophy and what impairment the tapping span test is indicative of in this condition. Eight patients with mild posterior cortical atrophy were recruited. Age- and severity-matched individuals with amnesic Alzheimer’s disease (n = 9) were also recruited as a control group. The participants were subjected to the tapping span test and several visuospatial working memory tests. The results of the tapping span and visuospatial working memory tests were worse for the posterior cortical atrophy group when compared with the control group. The results from the tapping span tests were strongly correlated with those from the visuospatial working memory tests. The tapping span test is a simple and potentially useful diagnostic tool for patients with mild posterior cortical atrophy, as it reflects visuospatial working memory function.

show abstract

New insights into atypical Alzheimer's disease in the era of biomarkers

Cited by 307 publications

References 100 publications

Structural (dys)connectivity associates with cholinergic cell density of the nucleus basalis of Meynert in Alzheimer’s disease

Structural (dys)connectivity associates with cholinergic cell density of the nucleus basalis of Meynert in Alzheimer’s disease

Provisional research criteria for the behavioral variant of Alzheimer’s disease A systematic review and meta-analysis

Visuospatial working memory dysfunction from tapping span test as a diagnostic tool for patients with mild posterior cortical atrophy

Contact Info

Product

Resources

About