Impact of Physical Activity on Successful Aging
Condition: Alzheimer Disease; Cognitive Impairment; Physical Activity
MeSH terms: Alzheimer Disease
Study type: Interventional

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Physical activity (PA); cognitive treatment (CT)
Intervention type(s): Other; Other
Intervention description(s): 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.; 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
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment
Keywords: alzheimer's disease, physical activity, cognitive training