<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03034746</url>
  </required_header>
  <id_info>
    <org_study_id>PRIN_2010</org_study_id>
    <nct_id>NCT03034746</nct_id>
  </id_info>
  <brief_title>Impact of Physical Activity on Successful Aging</brief_title>
  <official_title>Impact of Physical Activity on Successful Aging: Multidisciplinary Analysis of Mechanisms and Outcomes</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Universita di Verona</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Universita di Verona</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Emerging literature suggests that vascular factors might be involved in the pathogenesis of&#xD;
      Alzheimer's disease (AD). Other recent studies demonstrate the positive effects of physical&#xD;
      activity on cognitive and behavioral disturbances of patients with AD. Therefore, it has been&#xD;
      postulated that exercise enchantment in cerebral circulation is the physiological mechanism&#xD;
      that link physical exercise and reduction of AD symptoms. Consequently, a program of physical&#xD;
      activity could be considered one approach to counteract dementia by improving cerebrovascular&#xD;
      health.&#xD;
&#xD;
      However at this moment, it is not clear if the progressive brain vascular dysfunction and&#xD;
      hypoperfusion, associated with the β-amyloid deposition, might be reversed or stabilized by&#xD;
      an exercise intervention.&#xD;
&#xD;
      The aim of this study is to assess, in patients with AD, the influence of physical exercise,&#xD;
      compared to cognitive stimulation, on:&#xD;
&#xD;
        -  Cognitive function;&#xD;
&#xD;
        -  Independence in daily living and behavioral symptoms;&#xD;
&#xD;
        -  Vascular function Finally, to investigate the physiological processes on the basis of&#xD;
           the motor parameters' changes, the performances of the patients will be compared with&#xD;
           the performances of healthy young and old subjects.&#xD;
&#xD;
      MAIN OBJECTIVE: Investigate, in patients with Mild Cognitive Impairment (MCI) and AD, the&#xD;
      effects of a physical activity program, or cognitive stimulation on global cognitive&#xD;
      function.&#xD;
&#xD;
      SECONDARY OBJECTIVES: Investigate the effects of the two treatments on:&#xD;
&#xD;
        -  cognitive and motor performances,&#xD;
&#xD;
        -  independence in activities of daily living,&#xD;
&#xD;
        -  behavioral symptoms,&#xD;
&#xD;
        -  peripheral vascular function.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      STUDY DESIGN:&#xD;
&#xD;
      Randomised controlled, blinded clinical trial.&#xD;
&#xD;
      SUBJECTS:&#xD;
&#xD;
      The study will include 120 patients with definite diagnosis of MCI or AD and 30 young healthy&#xD;
      subjects and 30 old healthy subjects referred to the Research Unit associated with the&#xD;
      Department.&#xD;
&#xD;
      Patients will be regarded as suitable to participate if they fulfilled the following&#xD;
      criteria:&#xD;
&#xD;
        -  Mini Mental State Examination (MMSE) ≥ 8;&#xD;
&#xD;
        -  Performance Oriented Mobility Assessment ≥ 19 (POMA).&#xD;
&#xD;
      Exclusion criteria will be:&#xD;
&#xD;
        -  presence of other concurrent neurological diseases;&#xD;
&#xD;
        -  presence of other orthopaedic diseases involving the lower limbs and/or interfering with&#xD;
           standing position and/or walking;&#xD;
&#xD;
        -  presence of severe auditory and visual deficits not corrected;&#xD;
&#xD;
        -  abuse of alcohol or drugs;&#xD;
&#xD;
        -  psychiatric disorders,&#xD;
&#xD;
        -  severe behavioral disorders;&#xD;
&#xD;
        -  hearth and respiratory disease that interfere with the motor activity. The protocol was&#xD;
           be approved by the local ethics committee with number 2389. All participants will&#xD;
           perform a physiatric examination by a medical doctor of the Department of Neurological&#xD;
           and Movement Sciences. Written inform consent will be obtained from all participants&#xD;
           before inclusion in the study.&#xD;
&#xD;
      Participants who will meet the inclusion criteria will conduct a clinical and instrumental&#xD;
      evaluation at enrollment (T0) and after 6 months ± 15 days after the first visit (T1). The&#xD;
      assessment procedures will also be repeated after 3 months (T2) from T1.&#xD;
&#xD;
      ASSESSMENT PROCEDURES&#xD;
&#xD;
      Primary endpoints:&#xD;
&#xD;
      - score obtained in the Mini Mental State Examination.&#xD;
&#xD;
      Secondary endpoints:&#xD;
&#xD;
      - score obtained in a cognitive battery.&#xD;
&#xD;
      For MCI patients will be used:&#xD;
&#xD;
        -  Trial Making Test (Reitan,1958),&#xD;
&#xD;
        -  Rivermead Behavioral Memory Test (Wilson, 1989),&#xD;
&#xD;
        -  Tower of London (Shallice, 1982),&#xD;
&#xD;
        -  Dual Task (Della Sala et al., 1997),&#xD;
&#xD;
        -  Frontal Assessment Battery (Iavarone A et al., 2004).&#xD;
&#xD;
      For AD patients will be used:&#xD;
&#xD;
        -  Attention Matrix (Spinnler et al., 1987),&#xD;
&#xD;
        -  Alzheimer's Disease Assessment Scale (Rosen WG et al., 1984),&#xD;
&#xD;
        -  Frontal Assessment Battery (Iavarone A et al., 2004).&#xD;
&#xD;
           - score obtained in a motor skills assessment composed by:&#xD;
&#xD;
        -  6-Minute Walking Test (Ries JD et al., 2009),&#xD;
&#xD;
        -  gait analysis by GAITRite® System (Bilney B et al., 2003),&#xD;
&#xD;
        -  stabilometric assessments with Stability Line (Nashner LM and Peters JF, 1990),&#xD;
&#xD;
             -  score obtained in the test Instrumental Activity in Daily Living (Lawton MP and&#xD;
                Brody EM, 1969),&#xD;
&#xD;
             -  score obtained in the test Neuropsychiatric Inventory (Cummings JL et al., 1994),&#xD;
&#xD;
             -  peripheral vascular function measured by doppler.&#xD;
&#xD;
      To evaluate the effectiveness of motor treatment, compared to a cognitive treatment on motor&#xD;
      skills, cognitive skills, behavioral and autonomy in patients with cognitive decline, all&#xD;
      patients will be evaluated by motor, cognitive, behavioral and autonomy scales, at baseline,&#xD;
      after 6 months (T1), and after others 3 months (T2). A subgroup of 50% of patients will&#xD;
      undergo instrumental procedures to investigate the effects of treatments on cerebral blood&#xD;
      flow (arterial spin labeling).&#xD;
&#xD;
      TREATMENT PROCEDURES&#xD;
&#xD;
      The participants will be recruited and randomly assigned, according to the degree of&#xD;
      cognitive decline, to one of the 3 groups (7-8 subjects):&#xD;
&#xD;
        -  Physical Activity group (PA group): It will perform a program consist of 15 min of&#xD;
           warm-up, 60 min of aerobic and resistance training, and 15 min of cool-down.&#xD;
&#xD;
        -  Cognitive treatment group (CT group): The cognitive stimulation group will received a&#xD;
           rehabilitation program with multimodal repetitive stimulation in order to exercise and&#xD;
           reinforce the cognitive skills of the participant to slow/prevent the decline. In&#xD;
           particular the treatment will be focused on reorient the patient about his/her-self,&#xD;
           his/her history and his/her environment, to improve the memory skill by teaching&#xD;
           compensatory and restitutive strategies, to help the patient to the discussion about&#xD;
           everyday life and in particular to the everyday problems The PA and CT groups will be&#xD;
           homogeneous for clinical and demographic data, and participants will undergo 72&#xD;
           treatment group sessions, 60-minute/session, and 3 days/week for 6 consecutively months.&#xD;
&#xD;
      Both types of treatment will be balanced with different degrees of difficulty depending on&#xD;
      the state of disease severity .&#xD;
&#xD;
      o The control groups (CG) will not receive any such treatment during the study and they will&#xD;
      be evaluated by the same clinical and instrumental assessments.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2013</start_date>
  <completion_date type="Actual">October 2016</completion_date>
  <primary_completion_date type="Actual">May 2016</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Mini Mental State Examination</measure>
    <time_frame>0-6-9 months (change will be assessed)</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Trail Making Test</measure>
    <time_frame>0-6-9 months (change will be assessed)</time_frame>
    <description>For MCI patients (Reitan,1958)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rivermead Behavioral Memory Test</measure>
    <time_frame>0-6-9 months (change will be assessed)</time_frame>
    <description>For MCI patients (Wilson, 1989)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tower of London</measure>
    <time_frame>0-6-9 months (change will be assessed)</time_frame>
    <description>For MCI patients (Shallice, 1982)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dual Task</measure>
    <time_frame>0-6-9 months (change will be assessed)</time_frame>
    <description>For MCI patients (Della Sala et al., 1997)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Frontal Assessment Battery</measure>
    <time_frame>0-6-9 months (change will be assessed)</time_frame>
    <description>(Iavarone A et al., 2004)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Attention Matrix</measure>
    <time_frame>0-6-9 months (change will be assessed)</time_frame>
    <description>For AD patients (Spinnler et al., 1987)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Alzheimer's Disease Assessment Scale</measure>
    <time_frame>0-6-9 months (change will be assessed)</time_frame>
    <description>For AD patients (Rosen WG et al., 1984)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>6-Minute Walking Test</measure>
    <time_frame>0-6-9 months (change will be assessed)</time_frame>
    <description>(Ries JD et al., 2009)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>gait analysis by GAITRite® System</measure>
    <time_frame>0-6-9 months (change will be assessed)</time_frame>
    <description>(Bilney B et al., 2003)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>stabilometric assessments with Stability Line</measure>
    <time_frame>0-6-9 months (change will be assessed)</time_frame>
    <description>(Nashner LM and Peters JF, 1990),</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Instrumental Activity in Daily Living Scale (IADL)</measure>
    <time_frame>0-6-9 months (change will be assessed)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Neuropsychiatric Inventory Scale (NPI)</measure>
    <time_frame>0-6-9 months (change will be assessed)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>cerebral circulation</measure>
    <time_frame>0-6-9 months (change will be assessed)</time_frame>
    <description>measured MRI arterial spin labeling</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>peripheral vascular function</measure>
    <time_frame>0-6-9 months (change will be assessed)</time_frame>
    <description>measured by vascular doppler</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">90</enrollment>
  <condition>Alzheimer Disease</condition>
  <condition>Cognitive Impairment</condition>
  <condition>Physical Activity</condition>
  <arm_group>
    <arm_group_label>Alzheimer's Disease (G1)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>(G1) physical activity (PA)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Alzheimer's Disease (G2)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>(G2) cognitive treatment (CT)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Healthy Old Subjects (G1)</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Control group old</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Healthy young Subjects (G2)</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Control group young</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Physical activity (PA)</intervention_name>
    <description>It will perform a program consist of 15 min of warm-up, 60 min of aerobic and resistance training, and 15 min of cool-down.</description>
    <arm_group_label>Alzheimer's Disease (G1)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>cognitive treatment (CT)</intervention_name>
    <description>The cognitive stimulation group will received a rehabilitation program with multimodal repetitive stimulation in order to exercise and reinforce the cognitive skills of the participant to slow/prevent the decline. In particular the treatment will be focused on reorient the patient about his/her-self, his/her history and his/her environment, to improve the memory skill by teaching compensatory and restitutive strategies, to help the patient to the discussion about everyday life and in particular to the everyday problems</description>
    <arm_group_label>Alzheimer's Disease (G2)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  age ≥ 65 years;&#xD;
&#xD;
          -  Mini Mental State Examination (MMSE) ≥ 8;&#xD;
&#xD;
          -  Performance Oriented Mobility Assessment ≥ 19 (POMA).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  presence of other concurrent neurological diseases;&#xD;
&#xD;
          -  presence of other orthopaedic diseases involving the lower limbs and/or interfering&#xD;
             with standing position and/or walking;&#xD;
&#xD;
          -  presence of severe auditory and visual deficits not corrected;&#xD;
&#xD;
          -  abuse of alcohol or drugs;&#xD;
&#xD;
          -  psychiatric disorders,&#xD;
&#xD;
          -  severe behavioral disorders;&#xD;
&#xD;
          -  hearth and respiratory disease that interfere with the motor activity.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>65 Years</minimum_age>
    <maximum_age>90 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Nicola Smania</last_name>
    <role>Study Chair</role>
    <affiliation>Department of Neurological and Movement Sciences</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Federico Schena</last_name>
    <role>Principal Investigator</role>
    <affiliation>Department of Neurological and Movement Sciences</affiliation>
  </overall_official>
  <results_reference>
    <citation>Venturelli M, Lanza M, Muti E, Schena F. Positive effects of physical training in activity of daily living-dependent older adults. Exp Aging Res. 2010 Apr;36(2):190-205. doi: 10.1080/03610731003613771.</citation>
    <PMID>20209421</PMID>
  </results_reference>
  <results_reference>
    <citation>Venturelli M, Scarsini R, Schena F. Six-month walking program changes cognitive and ADL performance in patients with Alzheimer. Am J Alzheimers Dis Other Demen. 2011 Aug;26(5):381-8. doi: 10.1177/1533317511418956. Epub 2011 Aug 17.</citation>
    <PMID>21852281</PMID>
  </results_reference>
  <results_reference>
    <citation>Venturelli M, Magalini A, Scarsini R, Schena F. From Alzheimer's disease retrogenesis: a new care strategy for patients with advanced dementia. Am J Alzheimers Dis Other Demen. 2012 Nov;27(7):483-9. doi: 10.1177/1533317512459794. Epub 2012 Sep 13.</citation>
    <PMID>22984089</PMID>
  </results_reference>
  <results_reference>
    <citation>Venturelli M, Scarsini R, Muti E, Salvagno GL, Schena F. Sundowning syndrome and hypothalamic-pituitary-adrenal axis dysregulation in individuals with Alzheimer's disease: is there an association? J Am Geriatr Soc. 2013 Nov;61(11):2055-6. doi: 10.1111/jgs.12491. No abstract available.</citation>
    <PMID>24219216</PMID>
  </results_reference>
  <results_reference>
    <citation>Venturelli M, Ce E, Limonta E, Muti E, Scarsini R, Brasioli A, Schena F, Esposito F. Possible Predictors of Involuntary Weight Loss in Patients with Alzheimer's Disease. PLoS One. 2016 Jun 27;11(6):e0157384. doi: 10.1371/journal.pone.0157384. eCollection 2016.</citation>
    <PMID>27347878</PMID>
  </results_reference>
  <results_reference>
    <citation>Venturelli M, Sollima A, Ce E, Limonta E, Bisconti AV, Brasioli A, Muti E, Esposito F. Effectiveness of Exercise- and Cognitive-Based Treatments on Salivary Cortisol Levels and Sundowning Syndrome Symptoms in Patients with Alzheimer's Disease. J Alzheimers Dis. 2016 Jul 14;53(4):1631-40. doi: 10.3233/JAD-160392.</citation>
    <PMID>27540967</PMID>
  </results_reference>
  <results_reference>
    <citation>Crispoltoni L, Stabile AM, Pistilli A, Venturelli M, Cerulli G, Fonte C, Smania N, Schena F, Rende M. Changes in Plasma beta-NGF and Its Receptors Expression on Peripheral Blood Monocytes During Alzheimer's Disease Progression. J Alzheimers Dis. 2017;55(3):1005-1017. doi: 10.3233/JAD-160625.</citation>
    <PMID>27802234</PMID>
  </results_reference>
  <verification_date>January 2017</verification_date>
  <study_first_submitted>January 10, 2017</study_first_submitted>
  <study_first_submitted_qc>January 24, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 27, 2017</study_first_posted>
  <last_update_submitted>January 27, 2017</last_update_submitted>
  <last_update_submitted_qc>January 27, 2017</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 30, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Universita di Verona</investigator_affiliation>
    <investigator_full_name>prof. Federico Schena</investigator_full_name>
    <investigator_title>MD Full Professor</investigator_title>
  </responsible_party>
  <keyword>alzheimer's disease, physical activity, cognitive training</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Alzheimer Disease</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>November 29, 2017</submitted>
    <returned>August 22, 2018</returned>
    <submitted>August 1, 2019</submitted>
    <returned>September 10, 2019</returned>
    <submitted>June 3, 2021</submitted>
    <returned>June 25, 2021</returned>
    <submitted>July 23, 2021</submitted>
    <returned>August 17, 2021</returned>
  </pending_results>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03034746
org study id: PRIN_2010
nct id: NCT03034746
lead sponsor: 
has dmc: Yes
Emerging literature suggests that vascular factors might be involved in the pathogenesis of
      Alzheimer's disease (AD). Other recent studies demonstrate the positive effects of physical
      activity on cognitive and behavioral disturbances of patients with AD. Therefore, it has been
      postulated that exercise enchantment in cerebral circulation is the physiological mechanism
      that link physical exercise and reduction of AD symptoms. Consequently, a program of physical
      activity could be considered one approach to counteract dementia by improving cerebrovascular
      health.

      However at this moment, it is not clear if the progressive brain vascular dysfunction and
      hypoperfusion, associated with the β-amyloid deposition, might be reversed or stabilized by
      an exercise intervention.

      The aim of this study is to assess, in patients with AD, the influence of physical exercise,
      compared to cognitive stimulation, on:

        -  Cognitive function;

        -  Independence in daily living and behavioral symptoms;

        -  Vascular function Finally, to investigate the physiological processes on the basis of
           the motor parameters' changes, the performances of the patients will be compared with
           the performances of healthy young and old subjects.

      MAIN OBJECTIVE: Investigate, in patients with Mild Cognitive Impairment (MCI) and AD, the
      effects of a physical activity program, or cognitive stimulation on global cognitive
      function.

      SECONDARY OBJECTIVES: Investigate the effects of the two treatments on:

        -  cognitive and motor performances,

        -  independence in activities of daily living,

        -  behavioral symptoms,

        -  peripheral vascular function.
STUDY DESIGN:

      Randomised controlled, blinded clinical trial.

      SUBJECTS:

      The study will include 120 patients with definite diagnosis of MCI or AD and 30 young healthy
      subjects and 30 old healthy subjects referred to the Research Unit associated with the
      Department.

      Patients will be regarded as suitable to participate if they fulfilled the following
      criteria:

        -  Mini Mental State Examination (MMSE) ≥ 8;

        -  Performance Oriented Mobility Assessment ≥ 19 (POMA).

      Exclusion criteria will be:

        -  presence of other concurrent neurological diseases;

        -  presence of other orthopaedic diseases involving the lower limbs and/or interfering with
           standing position and/or walking;

        -  presence of severe auditory and visual deficits not corrected;

        -  abuse of alcohol or drugs;

        -  psychiatric disorders,

        -  severe behavioral disorders;

        -  hearth and respiratory disease that interfere with the motor activity. The protocol was
           be approved by the local ethics committee with number 2389. All participants will
           perform a physiatric examination by a medical doctor of the Department of Neurological
           and Movement Sciences. Written inform consent will be obtained from all participants
           before inclusion in the study.

      Participants who will meet the inclusion criteria will conduct a clinical and instrumental
      evaluation at enrollment (T0) and after 6 months ± 15 days after the first visit (T1). The
      assessment procedures will also be repeated after 3 months (T2) from T1.

      ASSESSMENT PROCEDURES

      Primary endpoints:

      - score obtained in the Mini Mental State Examination.

      Secondary endpoints:

      - score obtained in a cognitive battery.

      For MCI patients will be used:

        -  Trial Making Test (Reitan,1958),

        -  Rivermead Behavioral Memory Test (Wilson, 1989),

        -  Tower of London (Shallice, 1982),

        -  Dual Task (Della Sala et al., 1997),

        -  Frontal Assessment Battery (Iavarone A et al., 2004).

      For AD patients will be used:

        -  Attention Matrix (Spinnler et al., 1987),

        -  Alzheimer's Disease Assessment Scale (Rosen WG et al., 1984),

        -  Frontal Assessment Battery (Iavarone A et al., 2004).

           - score obtained in a motor skills assessment composed by:

        -  6-Minute Walking Test (Ries JD et al., 2009),

        -  gait analysis by GAITRite® System (Bilney B et al., 2003),

        -  stabilometric assessments with Stability Line (Nashner LM and Peters JF, 1990),

             -  score obtained in the test Instrumental Activity in Daily Living (Lawton MP and
                Brody EM, 1969),

             -  score obtained in the test Neuropsychiatric Inventory (Cummings JL et al., 1994),

             -  peripheral vascular function measured by doppler.

      To evaluate the effectiveness of motor treatment, compared to a cognitive treatment on motor
      skills, cognitive skills, behavioral and autonomy in patients with cognitive decline, all
      patients will be evaluated by motor, cognitive, behavioral and autonomy scales, at baseline,
      after 6 months (T1), and after others 3 months (T2). A subgroup of 50% of patients will
      undergo instrumental procedures to investigate the effects of treatments on cerebral blood
      flow (arterial spin labeling).

      TREATMENT PROCEDURES

      The participants will be recruited and randomly assigned, according to the degree of
      cognitive decline, to one of the 3 groups (7-8 subjects):

        -  Physical Activity group (PA group): It will perform a program consist of 15 min of
           warm-up, 60 min of aerobic and resistance training, and 15 min of cool-down.

        -  Cognitive treatment group (CT group): The cognitive stimulation group will received a
           rehabilitation program with multimodal repetitive stimulation in order to exercise and
           reinforce the cognitive skills of the participant to slow/prevent the decline. In
           particular the treatment will be focused on reorient the patient about his/her-self,
           his/her history and his/her environment, to improve the memory skill by teaching
           compensatory and restitutive strategies, to help the patient to the discussion about
           everyday life and in particular to the everyday problems The PA and CT groups will be
           homogeneous for clinical and demographic data, and participants will undergo 72
           treatment group sessions, 60-minute/session, and 3 days/week for 6 consecutively months.

      Both types of treatment will be balanced with different degrees of difficulty depending on
      the state of disease severity .

      o The control groups (CG) will not receive any such treatment during the study and they will
      be evaluated by the same clinical and instrumental assessments.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: Mini Mental State Examination
time frame: 0-6-9 months (change will be assessed)
measure: Trail Making Test
time frame: 0-6-9 months (change will be assessed)
description: For MCI patients (Reitan,1958)
measure: Rivermead Behavioral Memory Test
time frame: 0-6-9 months (change will be assessed)
description: For MCI patients (Wilson, 1989)
measure: Tower of London
time frame: 0-6-9 months (change will be assessed)
description: For MCI patients (Shallice, 1982)
measure: Dual Task
time frame: 0-6-9 months (change will be assessed)
description: For MCI patients (Della Sala et al., 1997)
measure: Frontal Assessment Battery
time frame: 0-6-9 months (change will be assessed)
description: (Iavarone A et al., 2004)
measure: Attention Matrix
time frame: 0-6-9 months (change will be assessed)
description: For AD patients (Spinnler et al., 1987)
measure: Alzheimer's Disease Assessment Scale
time frame: 0-6-9 months (change will be assessed)
description: For AD patients (Rosen WG et al., 1984)
measure: 6-Minute Walking Test
time frame: 0-6-9 months (change will be assessed)
description: (Ries JD et al., 2009)
measure: gait analysis by GAITRite® System
time frame: 0-6-9 months (change will be assessed)
description: (Bilney B et al., 2003)
measure: stabilometric assessments with Stability Line
time frame: 0-6-9 months (change will be assessed)
description: (Nashner LM and Peters JF, 1990),
measure: Instrumental Activity in Daily Living Scale (IADL)
time frame: 0-6-9 months (change will be assessed)
measure: Neuropsychiatric Inventory Scale (NPI)
time frame: 0-6-9 months (change will be assessed)
measure: cerebral circulation
time frame: 0-6-9 months (change will be assessed)
description: measured MRI arterial spin labeling
measure: peripheral vascular function
time frame: 0-6-9 months (change will be assessed)
description: measured by vascular doppler
arm group label: Alzheimer's Disease (G1)
arm group type: Experimental
description: (G1) physical activity (PA)
arm group label: Alzheimer's Disease (G2)
arm group type: Experimental
description: (G2) cognitive treatment (CT)
arm group label: Healthy Old Subjects (G1)
arm group type: No Intervention
description: Control group old
arm group label: Healthy young Subjects (G2)
arm group type: No Intervention
description: Control group young
intervention type: Other
intervention name: Physical activity (PA)
description: It will perform a program consist of 15 min of warm-up, 60 min of aerobic and resistance training, and 15 min of cool-down.
arm group label: Alzheimer's Disease (G1)
intervention type: Other
intervention name: cognitive treatment (CT)
description: The cognitive stimulation group will received a rehabilitation program with multimodal repetitive stimulation in order to exercise and reinforce the cognitive skills of the participant to slow/prevent the decline. In particular the treatment will be focused on reorient the patient about his/her-self, his/her history and his/her environment, to improve the memory skill by teaching compensatory and restitutive strategies, to help the patient to the discussion about everyday life and in particular to the everyday problems
arm group label: Alzheimer's Disease (G2)
criteria: 
gender: All
minimum age: 65 Years
maximum age: 90 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Nicola Smania
role: Study Chair
affiliation: Department of Neurological and Movement Sciences
last name: Federico Schena
role: Principal Investigator
affiliation: Department of Neurological and Movement Sciences
citation: Venturelli M, Lanza M, Muti E, Schena F. Positive effects of physical training in activity of daily living-dependent older adults. Exp Aging Res. 2010 Apr;36(2):190-205. doi: 10.1080/03610731003613771.
PMID: 20209421
citation: Venturelli M, Scarsini R, Schena F. Six-month walking program changes cognitive and ADL performance in patients with Alzheimer. Am J Alzheimers Dis Other Demen. 2011 Aug;26(5):381-8. doi: 10.1177/1533317511418956. Epub 2011 Aug 17.
PMID: 21852281
citation: Venturelli M, Magalini A, Scarsini R, Schena F. From Alzheimer's disease retrogenesis: a new care strategy for patients with advanced dementia. Am J Alzheimers Dis Other Demen. 2012 Nov;27(7):483-9. doi: 10.1177/1533317512459794. Epub 2012 Sep 13.
PMID: 22984089
citation: Venturelli M, Scarsini R, Muti E, Salvagno GL, Schena F. Sundowning syndrome and hypothalamic-pituitary-adrenal axis dysregulation in individuals with Alzheimer's disease: is there an association? J Am Geriatr Soc. 2013 Nov;61(11):2055-6. doi: 10.1111/jgs.12491. No abstract available.
PMID: 24219216
citation: Venturelli M, Ce E, Limonta E, Muti E, Scarsini R, Brasioli A, Schena F, Esposito F. Possible Predictors of Involuntary Weight Loss in Patients with Alzheimer's Disease. PLoS One. 2016 Jun 27;11(6):e0157384. doi: 10.1371/journal.pone.0157384. eCollection 2016.
PMID: 27347878
citation: Venturelli M, Sollima A, Ce E, Limonta E, Bisconti AV, Brasioli A, Muti E, Esposito F. Effectiveness of Exercise- and Cognitive-Based Treatments on Salivary Cortisol Levels and Sundowning Syndrome Symptoms in Patients with Alzheimer's Disease. J Alzheimers Dis. 2016 Jul 14;53(4):1631-40. doi: 10.3233/JAD-160392.
PMID: 27540967
citation: Crispoltoni L, Stabile AM, Pistilli A, Venturelli M, Cerulli G, Fonte C, Smania N, Schena F, Rende M. Changes in Plasma beta-NGF and Its Receptors Expression on Peripheral Blood Monocytes During Alzheimer's Disease Progression. J Alzheimers Dis. 2017;55(3):1005-1017. doi: 10.3233/JAD-160625.
PMID: 27802234
responsible party type: Principal Investigator
investigator affiliation: Universita di Verona
investigator full name: prof. Federico Schena
investigator title: MD Full Professor
mesh term: Alzheimer Disease
sharing ipd: No
submitted: November 29, 2017
returned: August 22, 2018
submitted: August 1, 2019
returned: September 10, 2019
submitted: June 3, 2021
returned: June 25, 2021
submitted: July 23, 2021
returned: August 17, 2021