Study of Neurological Aging Among People Living With HIV

Aging, Premature Clinical Trial

— SNAP  

Official title:

Study of Neurological Aging Among People Living With HIV (SNAP)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05678660
• Other study ID #: RSRB_STUDY00007234
• Secondary ID: R35NS122265
• Status: Recruiting
• Start date: July 6, 2022
• Est. completion date: June 5, 2028

Study information

• Verified date: April 2024
• Source: University of Rochester
• Contact: Moses Chilombe, BA
• Phone: +265999368845
• Email: moseschilombe[@]gmail.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

A prospective, exposure-control cohort study of older adults living with HIV comparing the neurological status of those who have had HIV infection for a longer period of time (long HIV group) to age, gender, and community-matched comparison group who have had HIV infection for a shorter period of time (short HIV group).

Description:

There is a substantial body of evidence that individuals with long-standing HIV infection experience accelerated neurological aging and prospective lifespan studies that incorporate neuropsychological and imaging outcomes are needed. Elevated risks of cerebrovascular disease are evident throughout the life course of persons living with HIV. Stroke risks are clearly increased in the first few months after antiretroviral initiation. Autopsy studies of adults with HIV 24-48 years of age showed all have vascular changes, specifically lymphocytic perivascular infiltration, thickening of arterial and arteriolar walls, widened perivascular space, hypertrophy of the vascular muscle layers and perivascular amyloid deposition. Even when excluding individuals with a history of stroke, cerebrovascular disease risk factors are associated with decreased cognitive capacity in persons with HIV. Basal ganglia enhancement on MRI indicative of decreased regional cerebral blood flow and blood brain barrier breakdown is associated with HIV dementia.

HIV-associated neurocognitive disorder is another manifestation of accelerated aging. Using diffusion tensor imaging and data from healthy controls to calculate an "brain age gaps" in individuals with HIV infection, the "brain age gap", is associated with plasma viral load and cognitive function. In an autopsy study comparing HIV+ persons age 36-60 years with age-matched controls, HIV showed increased amyloid beta immunostaining. The accumulation of these proteins may be one possible mechanisms of accelerated aging in HIV. Some have proposed that BBB breakdown secondary to vascular dysfunction may contribute to this deposition. Distal sensory polyneuropathy (DSPN), a common neurological comorbidity in HIV that also increases in frequency with age in HIV negative individuals. Despite extensive diagnostic evaluations, ~40% of people with a DSPN will have no clear underlying cause identified. DSPN is more common and complex in African population with additional underlying etiologies being medication toxicities and nutritional deficiencies.In the RAAZ study, investigators identified a high prevalence of DSPN among HIV infected individuals prior to ART initiation which is associated with low body mass index and food insecurity. More recent neuropathy studies have shown that folate deficiency may play a role in DSPN in Zambia with HIV+ individuals being especially susceptible. Epilepsy incidence shows a bimodal age distribution with the increased incidence of seizures and epilepsy in the elderly attributed to the increase of age-related and aging-related epileptogenic conditions. While the overall prevalence of epilepsy can be expected to increase with advanced age in HIV, identifying risk factors for this among persons for epilepsy among those with controlled systemic disease may offer important insights into the pathophysiology.

HIV-associated accelerated aging of the nervous system is thought to be related to ongoing low grade inflammation in the setting of treated HIV. Poor CNS penetration of some antiretroviral therapies (ARVs) has also been proposed as one problem contributing to neurological morbidity in systemically controlled HIV. ARV neurotoxicity is also important. Multiple studies have highlighted both the short and long term neurotoxicity of efavirenz. Darunavir and ritonavir may increase the risk of aging-related cerebral degeneration. Heneka 2020 proposed that COVID survivors may be at increased risk of neurological disorders due to direct negative effects of SARS-CoV-2, acceleration of pre-existing problems or de novo induction of neurodegenerative process. Poor complex motor performance in persons with HIV is associated with higher inflammatory burden. A recent report from Ghana found stroke admissions and mortality rates have increased since SARS-CoV-2's arrival.

In the SNAP Study, the investigators will utilize the existing consortia of neuro-HIV rural study sites to enroll 150 HIV+ adults >45 years of age stable on ARVs for at least 7 years and an age, gender, and community-matched comparison group of HIV+ adults stable on ARVs for 1-2 years. These individuals will undergo annual assessments for 6 years to evaluate their general and neurological health and the aging process that evolves during the 6 years of assessments.

Understanding whether or not PLWH experience accelerated aging of the nervous system will provide critical insights for health services planning as antiretroviral therapies allow PLWH to live into middle and late years. Identifying risk factors for specific neurologic aging issues will guide clinical care and screening and may inform regarding the pathophysiological mechanisms involved including the possibility that some therapies contribute to the long-term neurotoxicity of the condition.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: June 5, 2028
• Est. primary completion date: June 5, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 45 Years and older

Eligibility

Inclusion Criteria:

• For the short group, stable on ART for 1 year, but no more than 2 years.

• For long group, on ART for 7 or more years

Exclusion Criteria:

• Acute medical illness.

• Decisional impairment precluding informed consent as noted by clinicians providing care to the patient or by the research staff team members.

• Communication impairments-unable to hear or unable to speak.

• Being unable to communicate in English or in the dominant language at the study site (Tonga).

Related Conditions & MeSH terms

• Aging, Premature

Locations

Country	Name	City	State
Zambia	Chilenje Level 1 Hospital	Lusaka
Zambia	Chikankata Hospital	Mazabuka	Southern
Zambia	Monze Mission Hospital	Monze	Southern

Sponsors (3)

Lead Sponsor	Collaborator
University of Rochester	Centre for Infectious Disease Research in Zambia, National Institute of Neurological Disorders and Stroke (NINDS)

Country where clinical trial is conducted

Zambia, 

References & Publications (49)

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* Note: There are 49 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cognition - Zambian Mini-Mental Status Examination (zMMSE) - During enrolment	The zMMSE is an adaptation of the well-known MMSE which provides single summary score with a maximum of 30 points	baseline/during enrolment
Primary	Cognition - Zambian Mini-Mental Status Examination (zMMSE) - on Year 1 of evaluation	The zMMSE is an adaptation of the well-known MMSE which provides single summary score with a maximum of 30 points	Year 1 evaluation
Primary	Cognition - Zambian Mini-Mental Status Examination (zMMSE) - on Year 2 of evaluation	The zMMSE is an adaptation of the well-known MMSE which provides single summary score with a maximum of 30 points	Year 2 evaluation
Primary	Cognition - International HIV Dementia Scale (I-HDS) - on Year 3 of evaluation	The IHDS assesses registration, recall, motor speed and psychomotor speed and provides a single summary score of a maximum of 12 points	Year 3 evaluation
Primary	Cognition - International HIV Dementia Scale (I-HDS)- on Year 4 of evaluation	The IHDS assesses registration, recall, motor speed and psychomotor speed and provides a single summary score of a maximum of 12 points	Year 4 evaluations
Primary	Cognition - International HIV Dementia Scale (I-HDS) - on Year 5 of evaluation	The IHDS assesses registration, recall, motor speed and psychomotor speed and provides a single summary score of a maximum of 12 points	Year 5 evaluation
Primary	Cognition - International HIV Dementia Scale (I-HDS)- on Year 6 of evaluation	The IHDS assesses registration, recall, motor speed and psychomotor speed and provides a single summary score of a maximum of 12 points	Year 6 evaluation
Primary	Mental Health - The Alcohol Use Disorders Identification Test (AUDIT) -Baseline/during enrolment	The Alcohol Use Disorders Identification Test (AUDIT) is an alcohol screening instrument for patient self reporting. This 10-item alcohol screen helps identify persons who are hazardous drinkers or have active alcohol use disorders (including alcohol abuse or dependence). A score of 1 to 7 =low-risk consumption; 8 to 14 suggest harmful alcohol consumption, and =15 moderate-severe alcohol use disorder with a total score of 40.	Baseline/during enrolment
Primary	Mental Health - The Alcohol Use Disorders Identification Test (AUDIT) - on Year 1 of enrolment	The Alcohol Use Disorders Identification Test (AUDIT) is an alcohol screening instrument for patient self reporting. This 10-item alcohol screen helps identify persons who are hazardous drinkers or have active alcohol use disorders (including alcohol abuse or dependence). A score of 1 to 7 =low-risk consumption; 8 to 14 suggest harmful alcohol consumption, and =15 moderate-severe alcohol use disorder with a total score of 40.	Year 1 evaluation
Primary	Mental Health - The Alcohol Use Disorders Identification Test (AUDIT)- on year 2 of evaluation	The Alcohol Use Disorders Identification Test (AUDIT) is an alcohol screening instrument for patient self reporting. This 10-item alcohol screen helps identify persons who are hazardous drinkers or have active alcohol use disorders (including alcohol abuse or dependence). A score of 1 to 7 =low-risk consumption; 8 to 14 suggest harmful alcohol consumption, and =15 moderate-severe alcohol use disorder with a total score of 40.	Year 2 evaluation
Primary	Mental Health - The Alcohol Use Disorders Identification Test (AUDIT) - on year 3 of evaluation	The Alcohol Use Disorders Identification Test (AUDIT) is an alcohol screening instrument for patient self reporting. This 10-item alcohol screen helps identify persons who are hazardous drinkers or have active alcohol use disorders (including alcohol abuse or dependence). A score of 1 to 7 =low-risk consumption; 8 to 14 suggest harmful alcohol consumption, and =15 moderate-severe alcohol use disorder with a total score of 40.	Year 3 evaluation
Primary	Mental Health - Center for Epidemiologic Studies Depression Scale (CES-D)- on year 4 of evaluation	is a 7-item screen with a total score for the seven items ranging from 0 to 21. In most populations, 0-4: minimal anxiety / 5-9: mild anxiety / 10-14: moderate anxiety/ 15-21: severe anxiety.	Year 4 evaluation
Primary	Mental Health - Center for Epidemiologic Studies Depression Scale (CES-D)- on year 5 of evaluation	is a 7-item screen with a total score for the seven items ranging from 0 to 21. In most populations, 0-4: minimal anxiety / 5-9: mild anxiety / 10-14: moderate anxiety/ 15-21: severe anxiety.	Year 5 evaluation
Primary	Mental Health - Center for Epidemiologic Studies Depression Scale (CES-D)- on year 6 of evaluation	is a 7-item screen with a total score for the seven items ranging from 0 to 21. In most populations, 0-4: minimal anxiety / 5-9: mild anxiety / 10-14: moderate anxiety/ 15-21: severe anxiety.	Year 6 evaluation
Primary	Mental Health - The Generalized Anxiety Disorders Screen (GAD-7)- baseline/during enrolment	General Anxiety Disorder-7 (GAD-7). GAD-7 total score for the seven items ranges from 0 to 21. Scores of 5, 10, and 15 represent cut-points for mild, moderate, and severe anxiety, respectively. The higher the score, the more severe the anxiety.	Baseline
Primary	Mental Health - The Generalized Anxiety Disorders Screen (GAD-7)- baseline/during enrolment	General Anxiety Disorder-7 (GAD-7). GAD-7 total score for the seven items ranges from 0 to 21. Scores of 5, 10, and 15 represent cut-points for mild, moderate, and severe anxiety, respectively. The higher the score, the more severe the anxiety.	Baseline/during enrolment
Primary	Mental Health - The Generalized Anxiety Disorders Screen (GAD-7)- on year 1 of evaluation	General Anxiety Disorder-7 (GAD-7). GAD-7 total score for the seven items ranges from 0 to 21. Scores of 5, 10, and 15 represent cut-points for mild, moderate, and severe anxiety, respectively. The higher the score, the more severe the anxiety.	Year 1 evaluation
Primary	Mental Health - The Generalized Anxiety Disorders Screen (GAD-7)- on year 2 of evaluation	General Anxiety Disorder-7 (GAD-7). GAD-7 total score for the seven items ranges from 0 to 21. Scores of 5, 10, and 15 represent cut-points for mild, moderate, and severe anxiety, respectively. The higher the score, the more severe the anxiety.	Year 2 evaluation
Primary	Mental Health - The Generalized Anxiety Disorders Screen (GAD-7)- on year 3 of evaluation	General Anxiety Disorder-7 (GAD-7). GAD-7 total score for the seven items ranges from 0 to 21. Scores of 5, 10, and 15 represent cut-points for mild, moderate, and severe anxiety, respectively. The higher the score, the more severe the anxiety.	Year 3 evaluation
Primary	Mental Health - The Generalized Anxiety Disorders Screen (GAD-7)- on year 4 of evaluation	General Anxiety Disorder-7 (GAD-7). GAD-7 total score for the seven items ranges from 0 to 21. Scores of 5, 10, and 15 represent cut-points for mild, moderate, and severe anxiety, respectively. The higher the score, the more severe the anxiety.	Year 4 evaluation
Primary	Mental Health - The Generalized Anxiety Disorders Screen (GAD-7)- on year 5 of evaluation	General Anxiety Disorder-7 (GAD-7). GAD-7 total score for the seven items ranges from 0 to 21. Scores of 5, 10, and 15 represent cut-points for mild, moderate, and severe anxiety, respectively. The higher the score, the more severe the anxiety.	Year 5 evaluation
Primary	Mental Health - The Generalized Anxiety Disorders Screen (GAD-7)- on year 6 of evaluation	General Anxiety Disorder-7 (GAD-7). GAD-7 total score for the seven items ranges from 0 to 21. Scores of 5, 10, and 15 represent cut-points for mild, moderate, and severe anxiety, respectively. The higher the score, the more severe the anxiety.	Year 6 evaluation
Primary	Mental Health - An adaptation of the Harvard Trauma Questionnaire (HTQ)-baseline/during enrolment	Includes 10 traumatic events yielding a score of 0-10 and then 40 follow-up questions regarding post traumatic symptoms that will be delivered only to individuals scoring at least 1 on the initial 10 questions. The post traumatic symptom score will range is from 0-120.	Baseline/during enrolment
Primary	Mental Health - An adaptation of the Harvard Trauma Questionnaire (HTQ)- on year 1 of enrolment	Includes 10 traumatic events yielding a score of 0-10 and then 40 follow-up questions regarding post traumatic symptoms that will be delivered only to individuals scoring at least 1 on the initial 10 questions. The post traumatic symptom score will range is from 0-120.	Year 1 evaluation
Primary	Mental Health - An adaptation of the Harvard Trauma Questionnaire (HTQ)- on year 1 of evaluation	Includes 10 traumatic events yielding a score of 0-10 and then 40 follow-up questions regarding post traumatic symptoms that will be delivered only to individuals scoring at least 1 on the initial 10 questions. The post traumatic symptom score will range is from 0-120.	Year 2 evaluation
Primary	Mental Health - An adaptation of the Harvard Trauma Questionnaire (HTQ)- on year 3 of evaluation	Includes 10 traumatic events yielding a score of 0-10 and then 40 follow-up questions regarding post traumatic symptoms that will be delivered only to individuals scoring at least 1 on the initial 10 questions. The post traumatic symptom score will range is from 0-120.	Year 3 evaluation
Primary	Mental Health - An adaptation of the Harvard Trauma Questionnaire (HTQ)- on year 4 of evaluation	Includes 10 traumatic events yielding a score of 0-10 and then 40 follow-up questions regarding post traumatic symptoms that will be delivered only to individuals scoring at least 1 on the initial 10 questions. The post traumatic symptom score will range is from 0-120.	Year 4 evaluation
Primary	Mental Health - An adaptation of the Harvard Trauma Questionnaire (HTQ)- on year 5 of evaluation	Includes 10 traumatic events yielding a score of 0-10 and then 40 follow-up questions regarding post traumatic symptoms that will be delivered only to individuals scoring at least 1 on the initial 10 questions. The post traumatic symptom score will range is from 0-120.	Year 5 evaluation
Primary	Mental Health - An adaptation of the Harvard Trauma Questionnaire (HTQ) - on year 6 of evaluation	Includes 10 traumatic events yielding a score of 0-10 and then 40 follow-up questions regarding post traumatic symptoms that will be delivered only to individuals scoring at least 1 on the initial 10 questions. The post traumatic symptom score will range is from 0-120.	Year 6 evaluation
Primary	Frailty assessment - Body weight - baseline/during enrolment	Body composition describes percentages of fat, bone, and muscle in the human body. Body composition also represents a more accurate description of weight and provides a better understanding of the overall health of an individual. Measuring body composition is part of the frailty assessment. The smart scale will be used to capture a full body composition analysis, which includes the following measurement: Body weight in kilograms (kg).	Baseline/during enrolment
Primary	Frailty assessment - Body weight - on year 1 of evaluation.	Body composition describes percentages of fat, bone, and muscle in the human body. Body composition also represents a more accurate description of weight and provides a better understanding of the overall health of an individual. Measuring body composition is part of the frailty assessment. The smart scale will be used to capture a full body composition analysis, which includes the following measurements: Body Weight in kilograms (kg)	Year 1 evaluation
Primary	Frailty assessment - Body weight- on year 2 of evaluation	Body composition describes percentages of fat, bone, and muscle in the human body. Body composition also represents a more accurate description of weight and provides a better understanding of the overall health of an individual. Measuring body composition is part of the frailty assessment. The smart scale will be used to capture a full body composition analysis, which includes the following measurements: Body Weight in kilograms (kg)	Year 2 evaluation
Primary	Frailty assessment - Body weight - on year 3 of evaluation	Body composition describes percentages of fat, bone, and muscle in the human body. Body composition also represents a more accurate description of weight and provides a better understanding of the overall health of an individual. Measuring body composition is part of the frailty assessment. The smart scale will be used to capture a full body composition analysis, which includes the following measurements: Body Weight, Body Fat, Body Muscle, and the Body Mass Index (BMI).	Year 3 evaluation
Primary	Frailty assessment - Body weight on year 4 of evaluation	Body composition describes percentages of fat, bone, and muscle in the human body. Body composition also represents a more accurate description of weight and provides a better understanding of the overall health of an individual. Measuring body composition is part of the frailty assessment. The smart scale will be used to capture a full body composition analysis, which includes the following measurements: Body Weight in kilograms(kg)	Year 4 evaluation
Primary	Frailty assessment - Body weight - on year 5	Body composition describes percentages of fat, bone, and muscle in the human body. Body composition also represents a more accurate description of weight and provides a better understanding of the overall health of an individual. Measuring body composition is part of the frailty assessment. The smart scale will be used to capture a full body composition analysis, which includes the following measurements: Body Weight, Body Fat, Body Muscle, and the Body Mass Index (BMI).	Year 5 evaluation
Primary	Frailty assessment - Body weight - on year 6 of evaluation	Body composition describes percentages of fat, bone, and muscle in the human body. Body composition also represents a more accurate description of weight and provides a better understanding of the overall health of an individual. Measuring body composition is part of the frailty assessment. The smart scale will be used to capture a full body composition analysis, which includes the following measurements: Body Weight in kilograms(kg).	Year 6 evaluation
Primary	Frailty assessment - Body height- baseline/during enrolment	Body composition describes percentages of fat, bone, and muscle in the human body. Body composition also represents a more accurate description of weight and provides a better understanding of the overall health of an individual. Measuring body composition is part of the frailty assessment. The height scale will be used to capture height in meters (m).	Baseline/during enrolment
Primary	Frailty assessment - Body height- on year 1 of evaluation	Body composition describes percentages of fat, bone, and muscle in the human body. Body composition also represents a more accurate description of weight and provides a better understanding of the overall health of an individual. Measuring body composition is part of the frailty assessment. The height scale will be used to capture height in meters (m).	Year 1 of evaluation
Primary	Frailty assessment - Body height- on year 2 of evaluation	Body composition describes percentages of fat, bone, and muscle in the human body. Body composition also represents a more accurate description of weight and provides a better understanding of the overall health of an individual. Measuring body composition is part of the frailty assessment. The height scale will be used to capture height in meters (m).	Year 2 of evaluation
Primary	Frailty assessment - Body height- on year 3 of evaluation	Body composition describes percentages of fat, bone, and muscle in the human body. Body composition also represents a more accurate description of weight and provides a better understanding of the overall health of an individual. Measuring body composition is part of the frailty assessment. The height scale will be used to capture height in meters (m).	Year 3 of evaluation
Primary	Frailty assessment - Body height- on year 4 of evaluation	Body composition describes percentages of fat, bone, and muscle in the human body. Body composition also represents a more accurate description of weight and provides a better understanding of the overall health of an individual. Measuring body composition is part of the frailty assessment. The height scale will be used to capture height in meters (m).	Year 4 of evaluation
Primary	Frailty assessment - Body height- on year 5 of evaluation	Body composition describes percentages of fat, bone, and muscle in the human body. Body composition also represents a more accurate description of weight and provides a better understanding of the overall health of an individual. Measuring body composition is part of the frailty assessment. The height scale will be used to capture height in meters (m).	Year 5 of evaluation
Primary	Frailty assessment - Body height- on year 6 of evaluation	Body composition describes percentages of fat, bone, and muscle in the human body. Body composition also represents a more accurate description of weight and provides a better understanding of the overall health of an individual. Measuring body composition is part of the frailty assessment. The height scale will be used to capture height in meters (m).	Year 6 of evaluation
Primary	Frailty assessment - Body mass index- baseline/during enrolment	Body composition describes percentages of fat, bone, and muscle in the human body. Body composition also represents a more accurate description of weight and provides a better understanding of the overall health of an individual. Measuring body composition is part of the frailty assessment. The smart scale will be used to capture a full body composition analysis, which includes the Body Mass Index (BMI) in kilograms(kg). With the following interpretation below 18.5 - underweight range. between 18.5 and 24.9 - healthy weight range. between 25 and 29.9 - overweight range. between 30 and 39.9 - obese range.	Baseline/during enrolment
Primary	Frailty assessment - Body mass index- on year 1 of evaluation	Body composition describes percentages of fat, bone, and muscle in the human body. Body composition also represents a more accurate description of weight and provides a better understanding of the overall health of an individual. Measuring body composition is part of the frailty assessment. The smart scale will be used to capture a full body composition analysis, which includes the Body Mass Index (BMI) in kilograms(kg). With the following interpretation below 18.5 - underweight range. between 18.5 and 24.9 - healthy weight range. between 25 and 29.9 - overweight range. between 30 and 39.9 - obese range.	Year 1 of evaluation
Primary	Frailty assessment - on year 2 of evaluation	Body composition describes percentages of fat, bone, and muscle in the human body. Body composition also represents a more accurate description of weight and provides a better understanding of the overall health of an individual. Measuring body composition is part of the frailty assessment. The smart scale will be used to capture a full body composition analysis, which includes the Body Mass Index (BMI) in kilograms(kg). With the following interpretation below 18.5 - underweight range. between 18.5 and 24.9 - healthy weight range. between 25 and 29.9 - overweight range. between 30 and 39.9 - obese range.	Year 2 of evaluation
Primary	Frailty assessment - Body mass index- on year 3 of evaluation	Body composition describes percentages of fat, bone, and muscle in the human body. Body composition also represents a more accurate description of weight and provides a better understanding of the overall health of an individual. Measuring body composition is part of the frailty assessment. The smart scale will be used to capture a full body composition analysis, which includes the Body Mass Index (BMI) in kilograms(kg). With the following interpretation below 18.5 - underweight range. between 18.5 and 24.9 - healthy weight range. between 25 and 29.9 - overweight range. between 30 and 39.9 - obese range.	Year 3 of evaluation
Primary	Frailty assessment - Body mass index- on year 4 of evaluation	Body composition describes percentages of fat, bone, and muscle in the human body. Body composition also represents a more accurate description of weight and provides a better understanding of the overall health of an individual. Measuring body composition is part of the frailty assessment. The smart scale will be used to capture a full body composition analysis, which includes the Body Mass Index (BMI) in kilograms(kg). With the following interpretation below 18.5 - underweight range. between 18.5 and 24.9 - healthy weight range. between 25 and 29.9 - overweight range. between 30 and 39.9 - obese range.	Year 4 of evaluation
Primary	Frailty assessment - Body mass index- on year 5 of evaluation	Body composition describes percentages of fat, bone, and muscle in the human body. Body composition also represents a more accurate description of weight and provides a better understanding of the overall health of an individual. Measuring body composition is part of the frailty assessment. The smart scale will be used to capture a full body composition analysis, which includes the Body Mass Index (BMI) in kilograms(kg). With the following interpretation below 18.5 - underweight range. between 18.5 and 24.9 - healthy weight range. between 25 and 29.9 - overweight range. between 30 and 39.9 - obese range.	Year 5 of evaluation
Primary	Frailty assessment - Body mass index- on year 6 of evaluation	Body composition describes percentages of fat, bone, and muscle in the human body. Body composition also represents a more accurate description of weight and provides a better understanding of the overall health of an individual. Measuring body composition is part of the frailty assessment. The smart scale will be used to capture a full body composition analysis, which includes the Body Mass Index (BMI) in kilograms(kg). With the following interpretation below 18.5 - underweight range. between 18.5 and 24.9 - healthy weight range. between 25 and 29.9 - overweight range. between 30 and 39.9 - obese range.	Year 6 of evaluation
Primary	Frailty assessments - Grip strength- baseline/during enrolment	Grip strength will be assessed by dynamometry against international norms for age and SNAP_Protocol_V2.3_14June22 Page 7 of 12 Version Date: 2.3 14June22 gender and will be classified as weak, normal or strong.	Baseline
Primary	Frailty assessments - Grip strength - on year 1 of evaluation	Grip strength will be assessed by dynamometry against international norms for age and SNAP_Protocol_V2.3_14June22 Page 7 of 12 Version Date: 2.3 14June22 gender and will be classified as weak, normal or strong.	Year 1 evaluation
Primary	Frailty assessments - Grip strength- on year 2 of evaluation	Grip strength will be assessed by dynamometry against international norms for age and SNAP_Protocol_V2.3_14June22 Page 7 of 12 Version Date: 2.3 14June22 gender and will be classified as weak, normal or strong.	Year 2 evaluation
Primary	Frailty assessments - Grip strength- on year 3 of evaluation	Grip strength will be assessed by dynamometry against international norms for age and SNAP_Protocol_V2.3_14June22 Page 7 of 12 Version Date: 2.3 14June22 gender and will be classified as weak, normal or strong.	Year 3 evaluation
Primary	Frailty assessments - Grip strength- on year 4 of evaluation	Grip strength will be assessed by dynamometry against international norms for age and SNAP_Protocol_V2.3_14June22 Page 7 of 12 Version Date: 2.3 14June22 gender and will be classified as weak, normal or strong.	Year 4 evaluation
Primary	Frailty assessments - Grip strength-on year 5 of evaluation	Grip strength will be assessed by dynamometry against international norms for age and SNAP_Protocol_V2.3_14June22 Page 7 of 12 Version Date: 2.3 14June22 gender and will be classified as weak, normal or strong.	Year 5 evaluation
Primary	Frailty assessments - Grip strength- on year 6 of evaluation	Grip strength will be assessed by dynamometry against international norms for age and SNAP_Protocol_V2.3_14June22 Page 7 of 12 Version Date: 2.3 14June22 gender and will be classified as weak, normal or strong.	Year 6 evaluation
Primary	Frail assessment - Physical Activity- baseline/during enrolment	Physical activity will be scored from 0-100 based upon will be determined based upon self-report in response to a list of items of commonly undertaken activities in this population.	Baseline
Primary	Frail assessment - Physical Activity- on year 1 of evaluation	Physical activity will be scored from 0-100 based upon will be determined based upon self-report in response to a list of items of commonly undertaken activities in this population.	Year 1 evaluation
Primary	Frail assessment - Physical Activity- on year 2 of evaluation	Physical activity will be scored from 0-100 based upon will be determined based upon self-report in response to a list of items of commonly undertaken activities in this population.	Year 2 evaluation
Primary	Frail assessment - Physical Activity- on year 3 of evaluation	Physical activity will be scored from 0-100 based upon will be determined based upon self-report in response to a list of items of commonly undertaken activities in this population.	Year 3 evaluation
Primary	Frail assessment - Physical Activity- on year 4 of evaluation	Physical activity will be scored from 0-100 based upon will be determined based upon self-report in response to a list of items of commonly undertaken activities in this population.	Year 4 evaluation
Primary	Frail assessment - Physical Activity- on year 5 of evaluation	Physical activity will be scored from 0-100 based upon will be determined based upon self-report in response to a list of items of commonly undertaken activities in this population.	Year 5 evaluation
Primary	Frail assessment - Physical Activity- on year 6 of evaluation	Physical activity will be scored from 0-100 based upon will be determined based upon self-report in response to a list of items of commonly undertaken activities in this population.	Year 6 evaluation
Primary	Frail assessment - Time Gait- baseline/during enrolment	Gait speed is based upon a 15-foot times gait. Normative walking speeds are not available in this population, but decline over time (in the same participant) and comparison within the matched pair will be used to determine slowed gait.	baseline
Primary	Frail assessment - Time Gait- on year 1 of evaluation	Gait speed is based upon a 15-foot times gait. Normative walking speeds are not available in this population, but decline over time (in the same participant) and comparison within the matched pair will be used to determine slowed gait.	Year 1 evaluation
Primary	Frail assessment - Time Gait- on year 2 of evaluation	Gait speed is based upon a 15-foot times gait. Normative walking speeds are not available in this population, but decline over time (in the same participant) and comparison within the matched pair will be used to determine slowed gait.	Year 2 evaluation
Primary	Frail assessment - Time Gaiton year 3 of evaluation	Gait speed is based upon a 15-foot times gait. Normative walking speeds are not available in this population, but decline over time (in the same participant) and comparison within the matched pair will be used to determine slowed gait.	Year 3 evaluation
Primary	Frail assessment - Time Gait- on year 4 of evaluation	Gait speed is based upon a 15-foot times gait. Normative walking speeds are not available in this population, but decline over time (in the same participant) and comparison within the matched pair will be used to determine slowed gait.	Year 4 evaluation
Primary	Frail assessment - Time Gait- on year 5 of evaluation	Gait speed is based upon a 15-foot times gait. Normative walking speeds are not available in this population, but decline over time (in the same participant) and comparison within the matched pair will be used to determine slowed gait.	Year 5 evaluation
Primary	Frail assessment - Time Gait- on year 6 of evaluation	Gait speed is based upon a 15-foot times gait. Normative walking speeds are not available in this population, but decline over time (in the same participant) and comparison within the matched pair will be used to determine slowed gait.	Year 6 evaluation
Primary	Peripheral nerve health - Brief Peripheral Neuropathy (BPNS)- baseline/during enrolment	The brief peripheral neuropathy screen yields a dichotomous outcome (neuropathy present vs absent).	baseline/ during enroloment
Primary	Peripheral nerve health - Brief Peripheral Neuropathy (BPNS)- on year 1 of evaluation	The brief peripheral neuropathy screen yields a dichotomous outcome (neuropathy present vs absent).	Year 1 of evaluation
Primary	Peripheral nerve health - Brief Peripheral Neuropathy (BPNS)- on year 2 of evaluation	The brief peripheral neuropathy screen yields a dichotomous outcome (neuropathy present vs absent).	Year 2 evaluation
Primary	Peripheral nerve health - Brief Peripheral Neuropathy (BPNS)- on year 3 of evaluation	The brief peripheral neuropathy screen yields a dichotomous outcome (neuropathy present vs absent).	Year 3 evaluation
Primary	Peripheral nerve health - Brief Peripheral Neuropathy (BPNS)- on year 4 of evaluation	The brief peripheral neuropathy screen yields a dichotomous outcome (neuropathy present vs absent).	Year 4 evaluation
Primary	Peripheral nerve health - Brief Peripheral Neuropathy (BPNS)- on year 5 of evaluation	The brief peripheral neuropathy screen yields a dichotomous outcome (neuropathy present vs absent).	Year 5 evaluation
Primary	Peripheral nerve health - Brief Peripheral Neuropathy (BPNS)- on year 6 of evaluation	The brief peripheral neuropathy screen yields a dichotomous outcome (neuropathy present vs absent).	Year 6 evaluation
Primary	Peripheral nerve health - Heart Rate Variability(HRV)- baseline/during enrolment	Heart rate variability will measure autonomic function. Baseline heart rate will be assessed and a heart rate variability score produced with higher scores generally representing better autonomic function. Comparisons between the two groups and the individual participants HRV trajectory over time will be evaluated.	Baseline/during enrolment
Primary	Peripheral nerve health - Heart Rate Variability(HRV)- on year 1 of evaluation	Heart rate variability will measure autonomic function. Baseline heart rate will be assessed and a heart rate variability score produced with higher scores generally representing better autonomic function. Comparisons between the two groups and the individual participants HRV trajectory over time will be evaluated.	Year 1 evaluation
Primary	Peripheral nerve health - Heart Rate Variability(HRV) - on year 2 of evaluation	Heart rate variability will measure autonomic function. Baseline heart rate will be assessed and a heart rate variability score produced with higher scores generally representing better autonomic function. Comparisons between the two groups and the individual participants HRV trajectory over time will be evaluated.	Year 2 evaluation
Primary	Peripheral nerve health - Heart Rate Variability(HRV)- on year 3 of evaluation	Heart rate variability will measure autonomic function. Baseline heart rate will be assessed and a heart rate variability score produced with higher scores generally representing better autonomic function. Comparisons between the two groups and the individual participants HRV trajectory over time will be evaluated.	Year 3 evaluation
Primary	Peripheral nerve health - Heart Rate Variability(HRV)- on year 4 of enrolment	Heart rate variability will measure autonomic function. Baseline heart rate will be assessed and a heart rate variability score produced with higher scores generally representing better autonomic function. Comparisons between the two groups and the individual participants HRV trajectory over time will be evaluated.	Year 4 evaluation
Primary	Peripheral nerve health - Heart Rate Variability(HRV)- on year 5 of evaluation	Heart rate variability will measure autonomic function. Baseline heart rate will be assessed and a heart rate variability score produced with higher scores generally representing better autonomic function. Comparisons between the two groups and the individual participants HRV trajectory over time will be evaluated.	Year 5 evaluation
Primary	Peripheral nerve health - Heart Rate Variability(HRV)- on year 6 of evaluation	Heart rate variability will measure autonomic function. Baseline heart rate will be assessed and a heart rate variability score produced with higher scores generally representing better autonomic function. Comparisons between the two groups and the individual participants HRV trajectory over time will be evaluated.	Year 6 evaluation