Neuropsychological and neuroimaging markers in cerebral amyloid angiopathy: a cross-sectional population-based study
- Autores: Cristina Giménez Paños
- Directores de la Tesis: Aida Lago Martín (dir. tes.), Raúl Espert Tortajada (codir. tes.), Marien Gadea Doménech (codir. tes.)
- Lectura: En la Universitat de València ( España ) en 2024
- Idioma: español
- Número de páginas: 213
- Tribunal Calificador de la Tesis: Luis Moya Albiol (presid.), Pilar Delgado Martínez (secret.), Olga Pellicer Porcar (voc.)
- Programa de doctorado: Programa de Doctorado en Neurociencias por la Universitat de València (Estudi General)
- Materias:
- Enlaces
- Tesis en acceso abierto en: RODERIC
- Resumen
Dementia is an acquired disorder that is characterized by a decline in cognition involving one or more cognitive domains (i.e., attention, executive function, processing speed, language, memory).
In contrast, mild cognitive impairment (MCI) is an intermediate state between normal cognition and dementia in which there are objective cognitive impairments but no decline in overall level of function. While specific subtle changes in cognition can occur in normal aging, MCI can also be a precursor of dementia. Dementia may have more than one cause, particularly as the condition progresses and, especially, in older persons.
One of the most common causes of cognitive impairment is cerebral amyloid angiopathy (CAA), which is a small vessel disease (SVD) characterized by progressive amyloid beta (Aß)-peptide deposits within small-to medium-size blood vessels of the brain and leptomeninges. In the elderly, spontaneous intracerebral hemorrhage (ICH) is the most dramatic and immediately life-threatening sign of CAA. CAA is a risk factor for the development of dementia in previous studies. Even though cognitive impairment has been observed clinically in CAA, little is known about the frequency, severity, and comprehensive cognitive profile of patients clinically diagnosed with CAA after a lobar ICH.
We hypothesize that a proportion of patients with ICH-CAA may present with cognitive alterations (defined as an impairment of <1 SD relative to the reference group in 2 cognitive domains) similar to that of SVD vascular cognitive impairment (VCI). In addition, individuals with a greater burden of small vessel disease are more likely to experience moderate to severe cognitive impairment. The main aim of this study is to determine the neuropsychological profile of this cohort. Secondary aim includes to determine the association of cognitive domains with various cerebral SVD markers in this population.
Patients with a diagnosis of lobar and/or cortical ICH associated to CAA, based on the modified Boston criteria, were selected from the INHERIT (INtracerebral HEmoRrhage pRospectIve Study) database. Demographic and clinical data were collected, and a comprehensive neuropsychological assessment and a 1.5T and 3T brain magnetic resonance (MRI) was performed between 2016-2021 on patients greater-than or equal to sign 55 years old.
34 We have seen from our neuropsychological study that, overall, at a median delay of 15 months after the ICH, no process or subprocess were impaired in the cognitive assessment. However, the processes in which they have the lowest performance are processing speed with a t score of 42 ± 1.47 (mean ± standard deviation), followed by memory (44 ± 1.61) and planning (44 ± 1.97).
None of the patients in our cohort had symptoms of depression. On both, the state (Depression total state: t=49, SD=11,24; Dysthymia State: t=43, SD=13.56 and Euthymia State: t=52, SD=11.29) and the trait scale (Depression total trait: t=44, SD=9.96; Dysthymia Trait: t= 40, SD=10.22; Euthymia Trait: t= 45, SD 11.61), patients scored appropriately. The results of this analysis indicate that none of the patients in our cohort had depression symptoms. Similar results were observed with anxiety, with an appropriate severity (Anxiety State: t=51, SD=11.79) and frequency (Anxiety Trait: t=45, SD=8.27) level. In this population, no antidepressants and anxiolytic medications were prescribed.
Finally, among the 24 long-term survivors, 18 (75%) were independent (mRs 0-2) and 4 (17%) were dependent (mRs= 3) presenting a good ability to carry out basic activities of daily living (Bi = 98.60) as well as instrumental activities of daily living (LBi = 6.56).
Despite our cohort's adequate performance on all tests included in the cognitive assessment battery, we found strong associations between putative biomarkers of parenchymal CAA and cognitive domains. MTA was strongly associated with: Attention: p=0.002; adjusted R2= 31; Planning: p= 0.006; adjusted R2= 26; Verbal fluency: p=0.001; adjusted R2= 35); Language: p=0.001; adjusted R2= 36; Memory: p=0.003; adjusted R2= 29; Visuospatial: p=0.005; adjusted R2= 26; Visuoconstruction: p=0.006; adjusted R2= 26). Also, significant correlation was found between SVD total score and Verbal fluency p=0.032; adjusted R2= 15; Memory p=0.013; adjusted R2= 21; Visuoperception: p=0.0548; adjusted R2= 11; Visuospatial: p=0.037; adjusted R2= 14. Regarding the CAA total score, we found significant correlations with Memory: p=0.018; adjusted R2= 19; and Visuoperception: p=0.0326; adjusted R2= 15. As for GCA, we only found that it correlated significantly with Visuoperception: p=0.0221; adjusted R2= 17. In contrast, ICH volume was not significantly correlated with any cognitive process.
In conclusion, lobar ICH survivors have adequate cognitive and functional performance 15 months after the index event. Moreover, they do not present affective symptoms. However, we found that hippocampal atrophy (MTA) - an imaging marker traditionally associated with neurodegenerative disorders and memory impairment - is intimately related to potential future impairment in a wide range of cognitive processes.
