Table 2.
A description of studies examining the association of physical activity or exercise with metrics of hippocampal health.
| Study (Year) |
Sample (Age) | Hippocampus (Defined As) |
Summary of Findings |
|---|---|---|---|
| MORPHOLOGY | |||
| Cross-sectional Physical Activity Questionnaire | |||
| Significant Findings | |||
| Gorham et al. (2019) | Children (9-11 years) | Total, left, and right | Greater number of sports was associated with larger total and left HV, but not right HV. |
| Hashimoto et al. (2017) | Older adults (58-94 years) | Total | Hippocampal atrophy was associated with leisure-time physical inactivity. |
| Killgore et al. (2013) | Healthy adults (18-45 years) | Left and right | More minutes per week exercising was associated with greater left and right HV. |
| McEwen et al. (2015) | Patients with first-episode schizophrenia (18-45 years) | Total, left, and right | Lower PA was associated with decreased total and left HV, but not right HV. |
| Nunley et al. (2017) | Middle-aged adults with and without type 1 diabetes (35-60 years) | Total | Higher PA was associated with larger HV among type 1 diabetes subjects but not control subjects. |
| Okonkwo et al. (2014) | Late-middle-aged adults (40-65 years) | Total | Increasing age was associated with decreased HV, but effect was attenuated by 43% for active participants compared to inactive subjects. |
| Tarkka et al. (2019) | Male monozygotic twins (mean age 34.5 years) | Cluster in left | More-active co-twins had greater HV than less-active co-twins. |
| Null Findings | |||
| Bugg et al. (2011) | Older adults (55-79 years) | Total | PA alone did not account for unique variance in HV. |
| Head et al. (2012) | Older adults (mean age 72.5 years) | Total | PA alone did not account for unique variance in HV. Compared to the high-exercise group, the low-exercise group had decreased HV with increasing stress. |
| Jeon et al. (2020) | Older adults with healthy cognition or MCI (55-90 years) | Total | Retrospective report of midlife PA was not associated with HV. |
| Ortega et al. (2015) | Adults with HIV (mean age 41.6 years) | Total | No HV differences between physically active and sedentary groups. |
| Vemuri et al. (2012) | Older adults with healthy cognition or MCI (70-90 years) | Total | PA was not associated with HV. |
| Longitudinal Physical Activity Questionnaire | |||
| Significant Findings | |||
| Barha et al., (2020) | Older adults (70-79 years) | Left and right | Maintaining time spent walking over 10 years predicted smaller left HV for women and larger left HV for men. Null results were found for right HV. |
| Best et al., (2017) | Older adults (70-79 years) | Total | Maintaining time spent walking over 10 years predicted less reduction in HV. |
| Erickson et al., (2010) | Older adults (≥65 years) | Total | Greater PA predicted greater HV 9 years later. |
| Maltais et al., (2019) | Older adults at risk of cognitive decline (mean age 75.3 years) | Total | Any level of PA was associated with a reduced decline in HV compared to inactivity over 3 years. |
| Smith et al., (2014) | Older adults (65-89 years) | Total | Those with low PA and one or both APOE ε4 alleles (High Risk/Low PA) had decreased HV compared to those all other groups over 18 months (i.e., Low Risk/Low PA, High Risk/High PA, Low Risk/High PA). |
| Tan et al., (2017) | Older adults (≥60 years) | Total | Greater PA was associated with greater HV over 10 years. |
| Null Findings | |||
| Reijs et al., (2017) | Older adults with cognitive complaints and MCI (≥55 years) | Total | Lower HV was associated with conversion to AD-type dementia over 2.4 years, but it was not modulated by PA. |
| Cross-sectional Accelerometer | |||
| Significant Findings | |||
| (Hamer et al., 2018) | Middle-aged adults (40-69 years) | Left and right | More overall PA was associated with greater left and right HV. |
| Klaren et al. (2015) | Adults with multiple sclerosis (18-64 years) | Total | More time spent in moderate-to-vigorous PA was associated with greater HV, but light PA behavior and sedentary behavior were not. |
| Makizako et al. (2015) | Older adults with MCI (≥65 years) | Total | More time spent in moderate PA was associated with greater HV, but light PA and total PA were not. |
| Raichlen et al. (2019) | Middle-aged to older adults (45-80 years) | Left and right | More time spent in moderate-to-vigorous PA was associated with greater left and right HV. |
| Varma et al. (2015) | Older adults (≥60 years) | Total | Greater amount, duration, and frequency of total daily walking activity and low-intensity daily walking activity were associated with larger HV among women but not men. |
| Verma et al. (2016) | Older adults (≥60 years) | Left and right shape | Greater number of steps/day was associated with outward shape differences along the subiculum of the left and right hippocampus in women but not men. Greater low-intensity walking activity was associated with outward shape differences along the subiculum of the left hippocampus in women but not men. Moderate-to-vigorous PA was not significantly correlated with hippocampal shape in men or women. |
| Null Findings | |||
| Alosco et al. (2015) | Older adults with heart failure (50-85 years) | Total | Daily step count was not associated with HV. |
| Spartano et al. (2019) | Mean age 53 years | Total | HV was not associated with time spent in moderate-to-vigorous PA, light PA, or total PA. |
| Cross-sectional Cardiorespiratory Fitness | |||
| Significant Findings | |||
| Aghjayan et al. (2020) | Middle-aged adults with overweight or obesity (18-55 years) | Left, right, and shape | Higher CRF was associated with greater left HV, with outward shape differences along the surface of the subiculum and CA1 regions. Null results were found for right HV. |
| Boots et al. (2015) | Middle-aged adults at risk for AD (40-65 years) | Total | Higher CRF was associated with greater HV. |
| Bugg et al. (2012) | Older adults with obesity (65-75 years) | Total | CRF accounted for unique variance in HV after controlling for age, gender, and waist circumference. |
| Chaddock et al. (2010) | Preadolescent children (9-10 years) | Left and right | Higher-fit children had greater left and right HV compared to lower-fit children. |
| Chaddock-Heyman et al. (2015) | Breast cancer survivors (41-73 years) | Total, left and right anterior, and left and right posterior | Higher CRF was associated with greater total HV. Lower-fit cancer survivors had smaller total, left and right anterior, and left and right posterior HV than higher-fit control subjects. Lower-fit cancer survivors had smaller left posterior HV compared to lower-fit control subjects. |
| Dougherty et al. (2017) | Older adults at risk for AD (50-75 years) | Total | Higher CRF was associated with greater HV for women but not men. |
| Erickson et al. (2009) | Older adults (59-81 years) | Left and right | Higher CRF was associated with greater left and right HV. |
| Esteban-Cornejo et al. (2017) | Children with overweight or obesity (8-11 years) | Cluster in left | Higher CRF was associated with greater left HV. |
| Fletcher et al. (2016) | Older adults (55-87 years) | Total | Higher CRF was associated with greater HV. |
| Herting et al. (2012) | Male adolescents (15-18 years) | Left and right | Higher CRF was associated with greater left and right HV. |
| Makizako et al. (2013) | Older adults with MCI (≥65 years) | Cluster in left | Higher exercise capacity was associated with greater left HV. |
| McAuley et al. (2011) | Older adults (60-80 years) | Total | Higher CRF was associated with greater HV. |
| Motl et al. (2015) | Adults with multiple sclerosis (18-64 years) | Total | Higher CRF was associated with greater HV. |
| Ortega et al. (2017) | Children (mean age 9.7 years) | Left and right shape | CRF was associated with the shape (expansions/contractions) of the right hippocampus, but not the left hippocampal. |
| Stillman et al. (2018) | Young adults (20-38 years) | Left and right anterior, and left and right posterior | Higher CRF was associated with greater left anterior HV. |
| Szabo et al. (2011) | Older adults (60-80 years) | Total | Higher CRF was associated with greater HV. |
| Null Findings | |||
| Cole et al. (2020) | Older adults (60-76 years) | Total, left, and right | CRF was not significantly associated with total, left, or right HV. |
| Engeroff et al. (2018) | Older adults (≥65 years) | Left and right | CRF was not significantly associated with left or right HV. |
| Honea et al. (2009) | Older adults with healthy cognition and early-stage AD (≥65 years) | Total | No significant relationship of CRF with HV in either group. |
| Raichlen et al. (2019) | Middle-aged to older adults (45-80 years) | Left and right | CRF was not associated with left or right HV. |
| Wood et al. (2016) | Master athletes and active adults (45-73 years) | Left and right | CRF was not associated with left or right HV regardless of group. |
| Randomized Clinical Trials | |||
| Significant Findings | |||
| Erickson et al., (2011) | Sedentary older adults (55-80 years) | Left and right anterior, and left and right posterior | The aerobic group had an increase in left and right HV compared to the control group, which had a decrease in left and right HV over the 12-month intervention. Aerobic exercise increased left and right anterior HV but not left or right posterior HV compared to the control group, which had a decrease in left and right anterior HV but not left and right posterior HV. Greater improvements in CRF were associated with greater increases in left and right anterior HV, and left and right posterior HV. |
| Jonasson et al., (2016) | Sedentary old adults (64-78 years) | Total | Increased CRF following the 6-month intervention was associated with increased HV. |
| Leavitt et al. (2014) | Female patients with memory impairment and multiple sclerosis (33-44 years) | Total | The aerobic group showed an increase in HV following the 3-month intervention but the non-aerobic group did not. |
| Lin et al., (2015) | Women with early psychosis (16-60 years) | Total, left, and right | Aerobic exercise over 12 weeks was associated with increased HV, mainly related to increases in the left hippocampus. Changes in CRF did not differ significantly across the groups. |
| Maass et al., (2015) | Sedentary older adults (60-77 years) | Head, body, and tail | Increased CRF was associated with increased hippocampal head volume over 12 weeks, although hippocampal head volume did not increase overall in the exercise group. Null results were found for the body and tail. |
| Morris et al., (2017) | Older adults with early-stage AD (≥55 years) | Total | Increased CRF was associated with increased HV over 26 weeks. |
| Niemann et al., (2014) | Older adults (62-79 years) | Total, left, and right | Total and left HV increased in the aerobic exercise group over the 12-month intervention. Null results were found for the right hippocampus. Changes in CRF significantly explained variance in total and left HV, but not right HV. |
| Pajonk et al., (2010) | Men with chronic schizophrenia and matched healthy subjects (20-51 years) | Total | Among both aerobic exercise groups, HV increased by 14% over the 12-week intervention. Greater changes in CRF were associated with larger increases in HV. |
| Rosano et al., (2017) | Sedentary older adults at risk for mobility disability (70-89 years) | Total, left, and right | The PA group had greater left, right, and total HV following a 24-month intervention, although the right hippocampus was attenuated after controlling for regional baseline volume. |
| ten Brinke et al., (2015) | Women with probable MCI (70-80 years) | Total, left, and right | Compared with the control group, the aerobic group significantly improved left, right, and total HV following a 6-month intervention. |
| Thomas et al., (2016) | Sedentary, young to middle-aged adults (mean age 33.7 years) | Anterior | The 6-week exercise intervention significantly increased anterior HV, but it returned to baseline after an additional 6 weeks following the completion of the study. |
| Null Findings | |||
| Bunketorp Käll et al., (2015) | Students in grades 5 and 6 | Left and right | Neither left nor right HV differed significantly between groups, despite greater increases in CRF among the boys in the intervention group compared to the boys in the control group. |
| Frederiksen et al., (2018) | Patients with mild to moderate AD (50-90 years) | Left, right, and subfields | There was no effect of a 16-week intervention on HV or subfield volume. There was no significant correlation between CRF and HV. |
| Krogh et al., (2014) | Adults with major depression (18-60 years) | Left, right, and total | There was no difference in left, right, or total HV between groups following a 3-month intervention. Changes in CRF were not associated with changes in HV. |
| Malchow et al., (2016) | Patients with schizophrenia and healthy controls (18-60 years) | Total, left, right, and subfields | No significant changes in HV or subfield volume were found in patients or controls following a 3-month intervention. |
| Scheewe et al., (2013) | Patients with schizophrenia and healthy controls (18-48 years) | Left and right | The 6-month intervention did not have a significant effect on HV in patients or controls. |
| Tarumi et al., (2019) | Patients with amnestic MCI (55-80 years) | Total | The 12-month intervention did not have a significant effect on HV, despite significant improvements in CRF in the exercise group compared to the control group. |
| WHITE MATTER | |||
| White Matter Integrity | |||
| Cross-sectional Physical Activity Questionnaire | |||
| Significant Findings | |||
| Rodriguez-Ayllon, Derks, et al., (2020) | Children (10 years) | Cingulum ROI: hippocampal cingulum and cingulate gyrus | PA was negatively correlated with MD among all WM tracts of interest. There was no association between total PA and FA when controlling for sociodemographic factors. |
| Gow et al., (2012) | Older Adults (mean age 69.5 years at baseline) | ROI: FA and MD composite factors, consisting of 12 ROIS, including the rostral cingulum bundles | Higher PA was significantly associated with higher composite FA, but not MD. |
| Null Findings | |||
| Maltais et al., (2020) | Older adults without dementia ≥ 70 years. | ROI included the hippocampal cingulum | Null relationship between PA and FA. Associations between lower PA and faster MD worsening did not include the hippocampal cingulum. |
| Cross-sectional Accelerometer | |||
| Significant Findings | |||
| Burzynska et al., (2014) | Low-fit older adults (60-78 years) | ROI included the anterior cingulum, temporal lobe WM, and medial temporal/para-hippocampal WM | Light PA was associated with temporal ROI FA. In addition, sedentary behavior was related to lower parahippocampal FA. |
| Bracht et al., (2016) | Adults (mean age 25.5 years) | ROI: fornix and bilateral parahippocampal cingulum | Positive correlation between activity level and MWF, but not FA, in the right parahippocampal cingulum. |
| Null Findings | |||
| Burzynska et al., (2017) | Low-active older adults (60–80 years) | ROIs included the fornix and anterior and posterior cingulum (as well as parahippocampal WM) | Neither light nor moderate-to-vigorous PA were correlated with change in FA in hippocampal ROIs. |
| Cross-sectional Cardiorespiratory Fitness (CRF) | |||
| Significant Findings | |||
| Chen et al., (2020) | Midlife to older adults (55–65 years) | ROIs included the hippocampal cingulum & cingulate gyrus | Higher CRF was associated with higher FA in multiple WM tracts, including the hippocampal cingulum. |
| Ding et al., (2018) | Older adults with healthy cognition (mean age 66 years) or amnestic MCI (mean age 65 years) | Whole-brain | Higher CRF was associated with higher FA, and lower MD and RD, in a number of WM tracts, including the cingulum. |
| Harasym et al., (2020) | Post-menopausal women (mean age 59 years) | ROIs included the hippocampal cingulum & cingulate gyrus | Higher CRF related to higher AD in the hippocampal cingulum (but no associations with FA, MD, or RD). |
| Marks et al., (2011) | Sedentary older adults (60–76 years) | ROI: bilateral anterior, middle, and posterior cingulum | Higher CRF was associated with higher FA in the left middle cingulum. |
| Oberlin et al., (2016) | Older adults (60–81 years) | Whole-brain | Higher CRF was associated with higher FA in a number of WM tracts, including the fornix and cingulum. |
| Null Findings | |||
| Burzynska et al., (2014) | Low-fit older adults (60-78 years) | ROIs included the anterior cingulum, temporal lobe WM, and medial temporal/para-hippocampal WM | Null associations between CRF and FA in hippocampal regions. After controlling for age and gender, and association between higher temporal FA and CRF was reduced to trend level. |
| Burzynska et al., (2017) | Low-active older adults (60–80 years) | ROIs included the fornix and anterior and posterior cingulum (and parahippocampal WM) | Null associations between CRF and FA in hippocampal regions. |
| Clark et al., (2019) | Sedentary older adults (57 to 86 years) | Whole-brain | Null associations between CRF and both FA and MD. |
| Perea et al., (2016) | Sedentary older adults with early stage AD (mean age 72.35 years) | Whole-brain and ROI including bilateral cingulum bundles. | No significant positive association between CRF and cingulum FA, MD, RD, or AD, although there was a trending relationship between higher CRF and lower RD in the right cingulum. |
| Teixeira et al., (2016) | Older adults with amnestic MCI (57–80) | Whole-brain | Significant associations between higher CRF and higher FA, lower MD, lower RD, and lower AD did not include WM connections to the hippocampus. |
| Tseng et al., (2013) | Sedentary older adults (66–82 years) and master athletes (61–80 years) | Whole-brain | Higher CRF was associated with higher FA in multiple WM pathways, but not in hippocampal projections. (Notably, relative to sedentary older adults, master athletes showed significantly lower MD (but not FA) in the hippocampal cingulum.) |
| Randomized Clinical Trials | |||
| Significant Findings | |||
| Voss et al., (2013) | Sedentary older adults (55-80 years) | Lobular ROIs: Frontal, Temporal, Parietal, and Occipital | Increased CRF over the course of the 12-month intervention was associated with increased temporal, frontal, and parietal FA (but not AD or RD) in the exercise group but not the control group. There were no significant main effects of group assignment. |
| Burzynska et al., (2017) | Low-active older adults (60–80 years) | ROIs included the fornix and anterior and posterior cingulum (as well as parahippocampal WM) | Significant group by time interaction, such that fornix FA increased in the dance group after 6-months of intervention, and decreased in the walking and control groups. RD and MD showed significantly less decrease in the dance group. |
| Null Findings | |||
| Clark et al., (2019) | Sedentary older adults (57–86 years) | Whole-brain | Lower FA and higher MD following 6-months of an aerobic exercise intervention did not include hippocampal WM connections. |
| Sexton et al., (2020) | Older adults (60–85 years) | Whole-brain | No significant effects of a 3-month aerobic exercise intervention on FA, AD, or RD. |
| Svatkova et al., (2015) | Patients with schizophrenia and healthy controls (18–48 years) | Whole-brain | The exercise group demonstrated significant increases in FA over the 6-month intervention in several WM pathways, but not including connections to the hippocampus. |
| White Matter Volume | |||
| Cross-sectional Physical Activity Questionnaire | |||
| Null Findings | |||
| Ho et al., (2011) | Older adults (mean age 77.9 years) | Whole-brain | Self-reported PA (kcal/weekly expenditure) was not significantly associated with volume in WM of hippocampal connections. |
| Cross-sectional Cardiorespiratory Fitness (CRF) | |||
| Significant Findings | |||
| Esteban-Cornejo et al., (2019) | Children (7–11 years) | Whole-brain | Higher CRF was associated with greater WM volume in regions including the cingulate gyrus, among children with overweight/obesity but not children with BMI in the healthy range. |
| Honea et al., (2009) | Older adults with healthy cognition or early-stage AD (≥65 years) | Whole-brain and ROIs targeting hippocampal and parahippocampal regions | In early-stage AD, higher CRF was associated with greater WM volume in the left hippocampal ROI. No significant association between CRF and WM volume in cognitively normal older adults. |
| Null Findings | |||
| Erickson et al., (2007) | Post-menopausal women (58–80 years) | Whole-brain | Significant positive associations between CRF and WM volume did not include hippocampal tracts. |
| Gordon et al., (2008) | Young adults (20–28 years) and older adults (65–81) | Whole-brain | Null association between CRF and WM volume. |
| Randomized Clinical Trials | |||
| Null Findings | |||
| Colcombe et al., (2006) | Sedentary older adults (60–79 years) | Whole-brain | Greater WM volume over 6-months of intervention in the exercise group did not include hippocampal tracts. |
| FUNCTIONAL CONNECTIVITY | |||
| Cross-sectional Accelerometer | |||
| Significant Findings | |||
| Prakash et al., (2011) | Midlife adults with multiple sclerosis (30–58 years) | Left and right hippocampal seeds | Higher PA was associated with higher rsFC of both the left and right hippocampus to the posteromedial cortex |
| Null Findings | |||
| Voss et al., (2016) | Older adults (60–80 years) | Network ROIs, including the DMN | No significant associations among rsFC networks and physical activity. |
| Cross-sectional Cardiorespiratory Fitness | |||
| Significant Findings | |||
| Flodin et al., (2017) | Sedentary older adults (64–78 years) | Whole-brain analyses and left and right hippocampal and parahippocampal seeds | Right medial temporal lobe positively correlated with rsFC to frontal, parietal, and occipital areas and negatively correlated to the right thalamus and right occipital cortex. |
| Ikuta & Loprinzi, (2019) | Midlife adults (mean age 42.5 years) | Left and right hippocampal and parahippocampal seeds | Higher CRF was associated with more positive parahippocampal, but not hippocampal interhemispheric rsFC. |
| Stillman et al., (2018) | Young adults (20–38 years) | Left and right anterior and posterior hippocampal seeds | Higher CRF was associated with more positive rsFC of the left and right anterior hippocampus to regions including the frontal pole, middle frontal gyrus, and parahippocampus. Negative correlation between CRF and rsFC of right anterior hippocampus and right superior frontal gyrus. |
| Voss et al., (2016) | Older adults (60–80 years) | Network ROIs, including the DMN, and exploratory analysis of correlations between whole-brain seeds and the DMN core | Positive associations between CRF and rsFC in multiple networks, with most robust results within the DMN. Positive associations between fitness level and rsFC between the DMN core and several seeds, one of which extended to the left and right hippocampus. |
| Randomized Clinical Trials | |||
| Significant Findings | |||
| Burdette et al., (2010) | Older adults (70–85 years) | Whole-brain | After 4-months of intervention, the exercise group showed greater rsFC within the hippocampus, and from the hippocampus to the anterior cingulate cortex, as compared to controls. |
| Flodin et al., (2017) | Sedentary older adults (64–78 years) | Whole-brain analyses and left and right hippocampal and parahippocampal seeds, as well as network ROIs including the DMN | Increase in CRF following 6-months of intervention was associated with increased rsFC between the right hippocampus and frontal and parietal regions, and decreased rsFC between the left hippocampus and right precentral gyrus. Increase in CRF was correlated with increased rsFC between the DMN and left prefrontal cortex. No significant group by time interactions on rsFC. |
| Leavitt et al., (2014) | Female patients with memory impairment and patients with multiple sclerosis (33-44 years) | Left hippocampal seed | Aerobic exercise group, but not the control group, showed an increase in rsFC from the left to the right hippocampus. |
| Voss et al., (2020) | Older adults (60–80) years | ROIs included posterior and anterior hippocampus and parahippocampal cortex seeds | Effects of acute bouts of moderate intensity exercise in hippocampal-cortical rsFC in the DMN did not survive correction for multiple comparisons, but did predict increases in rsFC in these regions following 12-weeks of aerobic exercise training. |
| Weng et al., (2017) | Young adults (mean age 23.2 years) and older adults (mean age 66.3 years) | Network ROIs, including the DMN and a hippocampal cortical network | Single session of moderate intensity exercise were associated with rsFC within the hippocampus, and from the hippocampal cortical network to the medial prefrontal cortex, temporal pole, and intracalcarine cortex. |
| PERFUSION | |||
| Cross-sectional Physical Activity Questionnaire | |||
| Significant Findings | |||
| Zlatar et al., (2014) | Sedentary older adults at genetic risk for AD (52-81 years) | Left and right | Greater sedentary time was associated with greater left hippocampal perfusion for APOE ε4 carriers but not noncarriers. Null results were found for the right hippocampus. |
| Cross-sectional Cardiorespiratory Fitness (CRF) | |||
| Significant Findings | |||
| Chaddock-Heyman et al., (2016) | Preadolescent children (7-9 years) | Total, anterior, and posterior | Higher CRF was associated with greater total and posterior hippocampal perfusion, but not anterior. |
| Randomized Clinical Trials | |||
| Significant Findings | |||
| Alfini et al., (2016) | Master athletes (≥50 years) | Left and right | Perfusion decreased in the left and right hippocampus after 10 days of no exercise training. |
| Burdette et al., (2010) | Older adults (≤85 years) | Total | The exercise training group had greater hippocampal perfusion than the control group following a 4-month intervention. |
| Maass et al., (2015) | Sedentary older adults (60-77 years) | Total | Increased hippocampal perfusion for the exercise group following a 3-month intervention, but not the control group. Increased CRF was associated with greater hippocampal perfusion. |
| Pereira et al., (2007) | Adults (21-45 years) | Dentate gyrus, CA1 subfield, subiculum, and entorhinal cortex | Perfusion in the dentate gyrus increased over a 3-month intervention. Increases in dentate gyrus perfusion were associated with increases in CRF. |
Notes. Within the WM section of the table, the “Hippocampus (Defined As) column” describes studies that: (1) first used an exploratory, whole-brain approach and then identified regions of significance (“exploratory”); and (2) defined regions-of-interest, including WM tracts connecting to the hippocampus, prior to running analyses (“ROI”). Findings defined as null specifically pertain to results targeting the hippocampus. WMH is not included in this table as few studies have examined measurements of physical activity and localized lesions and none in relation to hippocampal WM connections. CRF = cardiorespiratory fitness, HV = hippocampal volume, PA = physical activity, MCI = mild cognitive impairment, AD = Alzheimer’s disease, HIV = human immunodeficiency virus, WM = white matter, FA = fractional anisotropy, MD = mean diffusivity, RD = radial diffusivity, AxD = axial diffusivity, MWF = myelin water fraction, rsFC = resting state functional connectivity.