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• Other relevant systemic diseases: hepatic             Specifically, although the neuropsychological bat-
       failure, renal failure, Obstructive Sleep Apnea     tery focuses especially on the evaluation of memory
       Syndrome (OSA)...                                   processes, attention and executive functions as po-
                                                           tential early markers of Alzheimer's disease, the neu-
   • Family history with special attention to the          ropsychological profile is completed by getting
       history of dementia or movement disorders,          information related to other cognitive domains such
       developmental delay or psychiatric disorders.       as language, visuospatial ability and visuoconstruc-
                                                           tion. All these data allow identifying the strengths
   • Regular drug treatment during the last 5              and weaknesses in the cognitive profile and cha-
       years.                                              racterizing, if necessary, the type of cognitive im-
                                                           pairment that an individual presents. Following table
4.3.4. General examination                                 lists the different tests that make up the neurops-
                                                           ychological battery of the Vallecas Project, as well
All subjects undergo a general and neurological            as the visit number in which they have been applied
standard examination: cranial nerves, muscle ba-           to all study participants.
lance, coordination, extrapyramidal system, gait, os-
teotendinous reflexes, midline release reflexes, etc. The  4.3.6. Determination of biomarkers
following parameters are analyzed in a special way:

• Gait disturbance                                         It is currently widely accepted that the molecular
                                                           changes associated with AD, including the forma-
• Handwriting                                              tion of amyloid plaques and neurofibrillary tangles
                                                           begin many years before the appearance of clini-
• Instrumental activities of daily living                  cal symptoms. In recent years, the need to define
                                                           and develop new early biomarkers of AD that allow
4.3.5. Neuropsychological Examination                      us to assess the risk and early diagnosis of the disease
                                                           has become clear. Thus, blood samples will be co-
The neuropsychological evaluation allows to explore        llected within the Vallecas Project for the study of
in a holistic way the various cognitive domains (gno-      genetic and biochemical markers. Samples are ob-
sias, attention, memory, language, praxis and exe-         tained according to the protocol "Collection and
cutive functions), as well as a series of variables        Processing of Human Blood Samples in the Vallecas
related to affectivity, behavior and level of auto-        Project" and processed to obtain the various frac-
nomy in the daily life of an individual. To do this, the   tions indicated in the protocol, which are stored at -
neuropsychologist can use different assessment ins-        80°C. On one hand, DNA is extracted from blood
truments, including clinical interviews, behavioral        cells to determine, by PCR and sequencing techni-
observation, cognitive tests and different question-       ques, genetic markers associated with the various
naires that allow for collecting information from both     polymorphisms in the following genes: APOE, CR1,
the individual and a reliable informant.                   BIN1, CLU, PICALM, ABCA7, SORL1, PRNP, GRM8, and
                                                           BACE1. These genes are studied using DNA obtained
The Vallecas Project neuropsychological examina-           from the extraction of samples from the first visit.
tion protocol has been designed to comprehensi-            Also, in the context of the project funded by the MI-
vely assess neuropsychological functioning of study        NECO (Projects RETOS) entitled "miRNA and lipid me-
participants, as well as their progression during the      tabolism markers as potential links between vascular
longitudinal follow-up.

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