RESUMO
Changes in hippocampal subfield volumes (HSV) along the Alzheimer's disease (AD) continuum have been scarcely investigated to date in elderly subjects classified based on the presence of ß-amyloid aggregation and signs of neurodegeneration. We classified patients (either sex) with mild dementia compatible with AD (n = 35) or amnestic mild cognitive impairment (n = 39), and cognitively unimpaired subjects (either sex; n = 26) using [11 C]PIB-PET to assess ß-amyloid aggregation (A+) and [18 F]FDG-PET to account for neurodegeneration ((N)+). Magnetic resonance imaging-based automated methods were used for HSV and white matter hyperintensity (WMH) measurements. Significant HSV reductions were found in A+(N)+ subjects in the presubiculum/subiculum complex and molecular layer, related to worse memory performance. In both the A+(N)+ and A+(N)- categories, subicular volumes were inversely correlated with the degree of Aß deposition. The A-(N)+ subgroup showed reduced HSV relative to the A-(N)- subgroup also in the subiculum/presubiculum. Combining all (N)- subjects, HSV were lower in subjects presenting significant cognitive decline irrespective of A+/A- classification (controlling for WMH load); these between-group differences were detected again in the presubiculum, but also involved the CA4 and granular layer. These findings demonstrate that differential HSV reductions are detectable both in (N)+ and (N)- categories along the AD continuum, and are directly related to the severity of cognitive deficits. HSV reductions are larger both in A+(N)+ and A+(N)- subjects in direct proportion to the degree of Aß deposition. The meaningful HSV reductions detected in the A-(N)+ subgroup highlights the strength of biomarker-based classifications outside of the classical AD continuum.
Assuntos
Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/análise , Disfunção Cognitiva/patologia , Hipocampo/patologia , Neuroimagem , Tomografia por Emissão de Pósitrons , Agregados Proteicos , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/metabolismo , Compostos de Anilina , Atrofia , Biomarcadores , Radioisótopos de Carbono , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/metabolismo , Feminino , Hipocampo/química , Hipocampo/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Masculino , Tamanho do Órgão , Compostos Radiofarmacêuticos , Tiazóis , Substância Branca/diagnóstico por imagemRESUMO
BACKGROUND: Studies of elderly subjects using biomarkers that are proxies for Alzheimer's disease (AD) pathology have the potential to document meaningful relationships between cognitive performance and biomarker changes along the AD continuum. OBJECTIVE: To document cognitive performance differences across distinct AD stages using a categorization based on the presence of PET-assessed amyloid-ß (Aß) burden and neurodegeneration. METHODS: Patients with mild dementia compatible with AD (nâ=â38) or amnestic mild cognitive impairment (aMCI; nâ=â43) and a cognitively unimpaired group (nâ=â27) underwent PET with Pittsburgh compound-B (PiB) assessing Aß aggregation (A+) and [18F]FDG-PET assessing neurodegeneration ((N)+). Cognitive performance was assessed with verbal and visual episodic memory tests and the Mini-Mental State Examination. RESULTS: The A+(N)+ subgroup (nâ=â32) showed decreased (pâ<â0.001) cognitive test scores compared to both A+(N)-(nâ=â18) and A-(N)-(nâ=â49) subjects, who presented highly similar mean cognitive scores. Despite its modest size (nâ=â9), the A-(N)+ subgroup showed lower (pâ<â0.043) verbal memory scores relative to A-(N)-subjects, and trend lower (pâ=â0.096) scores relative to A+(N)-subjects. Continuous Aß measures (standard uptake value ratios of PiB uptake) were correlated most significantly with visual memory scores both in the overall sample and when analyses were restricted to dementia or (N)+ subjects, but not in non-dementia or (N)-groups. CONCLUSION: These results demonstrate that significant Aß-cognition relationships are highly salient at disease stages involving neurodegeneration. The fact that findings relating Aß burden to memory performance were detected only at (N)+ stages, together with the similarity of test scores between A+(N)-and A-(N)-subjects, reinforce the view that Aß-cognition relationships during early AD stages may remain undetectable unless substantially large samples are evaluated.