Clinical trial: Hippocampal Sclerosis and Amnesia Not Due to Alzheimer's Disease (NCT02576821)

Eligibility criteria:
Inclusion Criteria:

        General inclusion criteria

          -  Be older than18 years old.

          -  Consulting in one of the centers (patients only)

          -  Sufficient cognitive capacities for the realization of the clinical and
             neuropsychological evaluations, left to the judgement by the investigator.

          -  Women old enough to procreate under effective contraception

          -  Signed consent

          -  Absence of general or systemic disorders that may interfere with cognition.

          -  If available before inclusion, absence of brain lesions as determined by MRI that may
             account for even part of the clinical presentation.

        Patients with Hippocampal sclerosis non AD (n=40)

        Clinical criteria :

          -  CDR (Clinical Dementia Rating Scale) = 0.5 or 1

          -  Progressive amnestic syndrome of the hippocampal type, defined by a free recall score
             ≤ 17/48 and a total recall score ≤ 40/48 on the FCSRT.

        Biological criteria : Absence of Profile suggestive of AD on the study of the biomarkers of
        the CSF (IATI ratio > 0.8)

        Patients with Alheimer's Disase (n=40)

        Clinical criteria :

          -  CDR (Clinical Dementia Rating Scale) = 0.5 or 1

          -  Typical amnesic AD : Progressive amnestic syndrome of the hippocampal type, defined by
             a free recall score ≤ 17/48 and a total recall score ≤ 40/48 on the FCSRT, associated
             or not with others cognitive impairment

          -  Posterior Cortical Atrophy : initial presentation of progressive visual or
             visuospatial impairment; absence of ophthalmologic impairment with evidence of complex
             visual and/or visuospatial disorder on examination; a relatively preserved episodic
             memory

          -  Logopenic progressive aphasia : word retrieval deficits in spontaneous speech and
             confrontation naming, impaired repetition of sentences, errors in spontaneous speech
             and naming (eg, phonological errors), and relative sparing of word and object
             knowledge and motor speech.

        Biological criteria : CSF biomarkers suggestive of AD defined on CSF.

        Patients with DLFT (n=20) :

        Clinical criteria :

          -  Modifications of the personality and the social conducts in the foreground

          -  Compatible brain imaging with the diagnosis : profile of atrophy and/or hypometabolism
             in TEP-FDG (or hypoerfusion in Spect) compatible with the diagnosis of DFT and/or
             absence of atypie Biological criteria : No AD profile on CSF biomarkers

        Patients with CBD/PSP (n=20) (Armstrong et al., 2013)

          1. Corticobasal syndrome :

               -  at least one of the following signs : limb rigidity or akinesia, limb dystonia,
                  limb myoclonusplus at least one of the following sign : orobuccal or limb
                  apraxia, e) cortical sensory deficit, alien limb phenomena (more than simple
                  levitation)

               -  Nonfluent/agrammatic variant of primary progressive aphasia: Effortful,
                  agrammatic speech plus at least one of: a) impaired grammar/sentence
                  comprehension with relatively preserved, single word comprehension, or b)
                  groping, distorted speech production (apraxia of speech)

          2. Progressive supranuclear palsy syndrome :

               -  Three of the following items present: a) axial or symmetric limb rigidity or
                  akinesia, b) postural instability or falls, c) urinary incontinence, d)
                  behavioural changes, e) supranuclear vertical gaze palsy or decreased velocity of
                  vertical saccades

        Normal controls (n=20):

        Absence of known psychiatric disorder Score on the Folstein Mini Mental Status (MMSE > or =
        27) Normal neuropsychological assessment for the age and the educational level

        Exclusion Criteria:

          -  Subject with a psychiatric evolutionary and/or badly checked pathology (left to the
             judgement of the investigator).

          -  Subject with a grave, severe or unstable pathology (left to the judgement of the
             investigator) the nature of which can interfere with the variables of evaluation.

          -  Epileptics subjects, badly tolerant MRI (1.5T, 3T or 7T), Subject presenting
             contraindications to the MRI (if necessary, a blood pregnancy test will be performed
             before 7T MRI) (Pacemaker or stimulating neurosensory or implantable defibrillator,
             cochlear implants, eye or cerebral ferromagnetic foreign bodies close to nervous
             structures, metallic prostheses, agitation of the patient : not cooperative or
             agitated patients, very young children, claustrophobics subjects, pregnant women,
             neurosurgical ventriculoperitoneal shunt valves, brace)

          -  Known or supposed histories (< or = 5 years) of severe alcoholism or misuse of drugs

          -  Vascular, inflammatory or expansive, visible lesion in the MRI which can interfere on
             the criteria of diagnosis.

          -  No health insurance

          -  Pregnant, breast-feeding woman or planning a pregnancy in two years of follow-up.

          -  For controls : anomaly detected on the MRI in the appreciation of the investigator
No condition on gender to be admitted to the trial.
Accepts Healthy Volunteers
Subject must be at least 18 Years old.


Patient description (medical language): A 70-year-old man comes to the office accompanied by his wife.  The patient has experienced progressive memory loss over the last years.  He needs help with some of his routine activities, such as paying bills.  The patient's wife says, "He used to be such an independent person, but now he needs help with many things, even finding direction to home!"  Medical history includes hypertension, hyperlipidemia, and type 2 diabetes mellitus.  Family history includes Alzheimer disease in his father.  MRI reveals diffuse cortical and hippocampal atrophy. The diagnosis of AD is made using the National Institute on Aging and the Alzheimer's Association (NIA-AA) criteria.

Patient description (patient's own words): I am a 70-year-old man, and I paid a visit to the doctor with my wife the other day. I noticed that I tend to forget small things and that my memory has decreased over the past few years. I even ask my wife to help me out with my daily routine. I used to be the one paying the bills, but now she has to give me a hand. My wife mentioned to the doctor that I used to be independent and that I tend to forget where we live. I suffer from hypertension, high cholesterol, and type 2 diabetes. My poor dad was suffering from Alzheimer disease, so I hope I'm not going to end the same way! I did an MRI and they found out that some part of my brain was decreasing. I also did an Alzheimer test.

Does the patient match the trial criteria? Entailment