*3.2. Tools/Variables Which Quantify Motor and Emotional Status at Patients with Neurodegenerative Diseases during Lockdown*

Neurodegenerative diseases are pathologies characterized by progressive dysfunction and neuronal damages due to the accumulation of proteins with altered biochemical properties. This process causes changes in neural interconnections affecting movement, speech, memory, intelligence and other brain functions, in accordance with the areas where changes occur in the central nervous system. Neurodegenerative diseases are associated with progressive cognitive and motor decline, having negative social, economic and financial impact, especially as the disease progresses.

In addition to the pathophysiology of neurodegenerative diseases, there are other risk factors that can aggravate and accelerate their evolution, such as lack of physical activity, sedentary lifestyle, weight gain/obesity or the association of other comorbidities (diabetes, atherosclerosis, hypertension). All these impediments to lifestyle, physical activity, eating habits, interpersonal communication and access to public health services were present during the periods of home regimentation imposed by the fight against the spread of coronavirus disease (COVID-19) [19].

As in the case of healthy adults, for patients with neurodegenerative diseases, specific online platforms were developed with questionnaires, semi-structured interviews or other telerehabilitation interventions at home. It was thus possible to quantify the progression of motor impairments induced by the decrease of controlled exercise training led by therapists, and alteration of cognitive status due to the lack of communication and social distance imposed during the period of isolation at home.

The following tools were used to assess the impact on emotional status, cognitive functions impairments, sleeping disorders and quality of life in home confinement: the Mini-mental Scale Examination (MMSE), which evaluates cognitive functions impairments [20–22]; the Montreal Cognitive Assessment (MOCA) [23]; the Geriatric -Depression Scale (GDS) [24,25]; Beck Depression Inventory-II (BDI-II), with score from 0 to 63, and high values means an increasing level of depression [26,27]; the Cognitive Emotion Regulation Questionnaire (CERQ) [28]; Social Support (SOZU-K) [29]; the Brief Resilience Scale (BRS) [30]; State Trait Anxiety Inventory (STAI); Optimist-5 point Scale; Quality of Life (QOL); Hoehn and Yahr (HY), Quality of Life short version (SF-8); Mental Component Summary (MCS); Motor experiences daily living (UPDRS) [10]; New-onset/worsening of sleep (NOWS), Restless legs syndrome (RLS), REM Sleep Behavior Disorder (REMBD), Item Content Validity Index (I-CVI), Scale Content Validity Index (S-CVI), Scale content validity Index Universal agreement (S-CVI-UA); Likert Scale; Sleep Disordered Breathing (SDB) [31].

Other variables reflect declining physical activity during lockdown, such as Physical Activity Readiness Questionnaire (PAR-Q), Physical Activity Level (PALs) [19,32], Physical Activity Scale for the elderly (PASE), Physical Activity Level (PALs), Physical Activity Readiness Questionnaire (PAR-Q), Physical Activity Scale for the elderly (PASE) [13,32] and Metabolic equivalents minutes/week (MET) [33].

Other tools can assess signs and symptoms of neurodegenerative diseases related to motor and cognitive dysfunctions well as their changes during the period of social isolation imposed by the spread of SARS infection—Cov-2: for Alzheimer' Disease; these include the Consortium to Establish a Registry for Alzheimer's Disease (CERAD-Plus) [19], the Clinical Dementia Rating Scale (CDR) [34], Hamilton Depression Rating (HAMD), Epworth Sleepiness Scale (ESS), Activities Daily Living (ADL) and Neuropsychiatric Inventory (NPI) [35].

Another autoimmune neurodegenerative disease which affects acetylcholine receptors from the level of the postsynaptic membrane of the end plate, Myasthenia gravis, was monitored through MG Quality of Life (MGQOL15), MG Activity of Daily Living (MGADL, Myasthenia Gravis Foundation of America staging (MGFA Scale), Hospital Anxiety and Depression Scale HADS) with a score range between 0–21, where increased values mean worsening depression and anxiety [36].

In Parkinson's Disease (PD), the neuropathological mechanism entails the loss of pigmented dopaminergic from the brain nuclei belonging to the black substance of the midbrain with production of atypical proteins, called Lewy bodies, subsequently altering the cortico-thalamo-cortical pathways with pathological consequences on the motor and cognitive behavior of the body. Therefore, motor deficiencies such as tremor, bradykinesia, gait disorders and stiffness as well as cognitive impairments, could be quantified through the Personalized Parkinson Project (PPP) [37]; Perceived Stress Scale (PSS) [38]; Unified Parkinson's Disease Rating Scale (UPDRS); Parkinson Anxiety Scale (PAS); Ruminative Response Scale (RRS) [4]; Physical Component Summary (PCS); Patient global impression of change Scale (PGIC), a scale with a score between 1 to 7, which investigates changes in motor and non-motor disorders in Parkinson's Disease; Hospital Anxiety and Depression Scale HADS) [10] and Sleep-Scales for Outcomes Parkinson's Disease (SCOPA-sleep) [39].

In four papers, monitoring patients with MCI has demonstrated the importance of intervention in various ways of physical activity delivered through online platforms, telephone interviews, or with dedicated applications on mental, affective and motor status. So, for 12 older adults of which six women and six men, with mild cognitive impairment, each carrying a polar heart sensor network, and for 8 weeks participated in a fitness and dance training program (two sessions of 90 min/week) delivered through the DIADEM platform, demonstrated improved cardiac performance, benefits in mental functions and enhanced motor status with better walking speed and step length. Monitoring was performed by heart rate recordings and by using the following instruments: MMSE, PAR-Q, GDS and CERAD-Plus [19]. During the pandemic lockdown, such interventions can efficiently compensate for the detraining due to combating the spread of coronavirus disease, while maintaining adequate muscle tone and motor skills.

For 177 older adults with mild cognitive impairment (50), Alzheimer' disease (105) and dementia with Lewy bodies, which performed activities daily living (ADL) stimulated by caregivers, demonstrated delayed mental and physical deterioration. Monitoring was demonstrated by evaluation of the scores of MOCA, NPI, HAMD, and ESS tools [35]. Another study investigated by telephone semi-structured interview, 4710 patients of which 2809 female and 1901 male, split in 2355 pairs with caregivers, with Alzheimer' disease, Dementia with Lewy body disease, Frontotemporal dementia and Vascular dementia, which performed activities daily living (ADL). Monitoring was performed through CDR. In this situation, increased caregivers stress risk has been estimated for patients, due to clinical features, lifestyle, dislike of continuity in medical care and deterioration of mental and emotional status of patients with dementia during restrictions imposed by spread SARS-CoV-2 infection. A prospective study discusses the importance of continuing physical activity at home during isolation in the COVID-19 pandemic. This includes moderate effort activity for 150 min/week, 75 min. of sustained effort/week and a strength training intervention provided by an app-based workout with online partners. The measurement of beneficial effects could be carried out through MET and the study includes participants of over 40% Latin America female, Caribbean female and other males and females in developed countries [33].

In another paper, 38 patients with moderate Myasthenia Gravis (not associated with COVID-19), were treated with prednisolone and azathioprine, and physical exercise training consisting of walking, yoga and moderate physical activity delivered through online platforms. Evaluation was carried out by specific tools: MGFA, MGQOL 15, MGADL, HADS and PSQI, which demonstrated worsening wellbeing life quality, anxiety and depression during home confinement [36].

In seven other studies, the evolution of patients with Parkinson's Disease in the restrictive period imposed by the COVID-19 pandemic was followed. A total of 88 older adults with PD were divided into an experimental (45) and control group (43). Phone interviews were carried out about ADL during lockdown using the specific tools: PASE, HADS and PALs. Evaluation revealed worsening motor impairments with increasing dyskinesia, tremor, freezing of gait, instability stance, muscles pain, rigidity and cognitive disorders, which were augmented sleep dysfunction, depression, anxiety, feeling stressed, lack of concentration and attention [36]. In another paper, investigations were carried out in 832 patients with PD, who were performing moderate walking training for one hour/day. The authors discuss the increasing motor and non-motor impairments during isolation at home assessed by RLS, REMBD, NOWS, I-CVI, S-CVI, S-CVI-UA, Likert Scale, VAS and the SDB scale. Through following these instruments, changes were evaluated in sleep quality, degrees of depression, anxiety, mood and poor life quality [31].

Another study with 100 older adults (45 women and 55 men with PD in the experimental group) and 100 caregivers, were assessed through online questionnaires about physical activity during the imposed home isolation required to combat the spread of COVID-19. The variables used showed, in particular, the alteration of the MCS score in females with PD due to weight loss, lack of exercise (37%) or unhealthy behavioral habits; for caregivers, there were serious concerns (47%) regarding the decrease in PCS score, through increasing stressors, smoking or changes in emotional and affective status during lockdown [10].

In a preliminary study on the stay at home mandate, a self-questionnaire was carried out with 36 patients by mobile based-neurocognitive assessment with PD, of which 53.6% were female and 46.4% were male, regarding physical activity/week, number of active days and average time allocated for physical exercise. Motor and neurocognitive patterns were quantified and performed by using the scales: MTA, MCA, NFI, SWCT and MMSE, which found decreases in motor skills, speech neurocognitive tasks and wellbeing life quality in approximately 80% of the patients with PD [40].

Another paper investigated the impact of the stay at home mandate for 517 adults with PD subject to an international online study, carried out over the course of 12 weeks, in 14 languages with a 64-item questionnaire. The Parkinson's patients were interrogated on online platforms about weekly physical activity from light physical activity to vigorous physical training and were assessed through SWEMWBS (7–35), PSQI and IPAQ-SF scales. The results showed declining motor functions, quality of sleep, negative feelings and worsening wellbeing of emotional and affective conditions. However, unlike young counterparts, there was greater resistance to stressors during lockdown and greater emotional resistance to older adults with PD [41].

The association of an external stressor, such as the COVID-19 pandemic, has worsened the motor and cognitive symptoms shown with 358 Parkinson's patients (38.5% female and 62.5% male) who participated in an online study with cognitive and psychological measurements. Patients participated in physical activity for 4 h/week, and their evaluation through PPP, PSS, PAS, RRS, BRS, CERQ, MoCA, SCOPA-sleep, STAI and BDI-II demonstrated worsening motricity with augmentation tremors, rigidity, pain, instability balance, and impairments of gait, but also aggravation of mental, emotional and sleep disorders [39].

The impact of the COVID-19 lockdown was evaluated with a web-based survey for 142 PD patients, of whom 41% were female and 50% were male, belonging to a community dwelling. They performed ADL and walking training. The instruments used for evaluation in quarantine were PAM-13 (0–100 score), which is a validated self-reported questionnaire measuring confidence, self-management, motor skills and cognition. Evaluation using a four-point Likert Scale demonstrated negative impact for 37.3% of the cases. The need for social care for these patients was found to be effective, especially due to the period of restrictions imposed by the COVID-19 pandemic, as approximately 24.8% of participants need caregivers [42].

The literature reveals substantial information about types of PA that were agreed upon by patients with neurodegenerative diseases.

Physical Activity in Neurodegenerative Diseases (MCI, AD, DLB, MG FTD and PD)

Physical activity (PA) has been studied in terms of types of physical activity and is presented in Figure 3.

**Figure 3.** Type of physical activity for patients with neurodegenerative diseases [9,13,26,30–35,38,39,41].

Table 2 presents the tools discussed, the characteristics, physical activities performed, interventions and conclusions derived from the studies on patients with neurodegenerative diseases.


*J. Clin. Med.* **2022**, *11*, 597



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**Table 2.** *Cont.*

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The relationship between PA and anxiety and depression levels has also been a problem in the pandemic period for PD patients. In this period, PA has experienced substantial changes and even leisure times, household and activities over the course of one week could improve PA levels.

Another study found the lockdown and consequent reduced PA was shown to increase anxiety in more than 68.9% of PD patients, aged 65, who showed preference for household activities [32].

Chen [35] took into consideration the relationship between PA and cognitive, neuropsychiatric symptoms and observed that PA had the most important decrease during one year with a DLB group of patients (*p* ≤ 0.001). At the same time, the PA level showed a sudden decrease and was correlated with the MMSE score.

The impact of COVID-19 for PD patients could be approached in relation to screen time and PA (less than 1 h/day, or more than 1 h/day). PA of more than 1 h/day has been shown to protect against sleep disorders [35].

Motor and non-motor symptoms are related to PA in PD patients; PA involves a decrease in symptoms by 50% for PD patients [40]. PA influences mental wellbeing [41] by improving mood and physical health. The COVID-19 pandemic has created the situation in which low PA can exacerbate cognitive issues in neurodegenerative diseases. This research found moderate PA and walking to decrease by 22–26% during lockdown and the sedentary activity led to sitting increasing by 27.2%.

Thus, the PA and sleep could be considered a predictor for wellbeing and would be interesting to study this in the long term effect.

PA in PD patients has been shown to decrease during COVID-19 and aggravate motor symptom and psychological distress. This could be correlated with worsening of PD symptoms severity and perceived stress [39].

For these patients, the authors confirm that 46.6% of respondents were less active during the pandemic period, but surprisingly, there was no correlation found between time of PA and perceived stress (Pearson correlation R = 0.07, *p* = 0.195).

Yogev [42] discuss the concept of activation in case of PD. This concept also includes PA, and they observed that people who had the highest levels in activity also had an excellent approach to self-management.

The study revealed that more than 67.8% of PD patients reported worsening of symptoms due to cessation of PA, but in the cases of high levels in activity, 69.7% of patients exercised 3–5 times/week or every day using an online application. The PA included stretching, yoga and stationary biking.

The authors concluded that two-thirds of respondents declared a worsening of symptoms, of which, PA was the principal factor.

Müller [33] carried out an analysis of the relationship between COVID-19 and physical activity and observed PA to decrease by 20% and sitting time increased by over 28%. He also took into consideration the anti-inflammatory effect of PA and the reduced effect of IL6 (interleukin 6) that may increase the fight against viral diseases, such as COVID-19.

In this context, exercise prescription should be revised to develop particular aspects such as endurance, resistance, balance exercises or outdoor activities.

This aspect is more important due to the consequences including risk of several chronic diseases, much more because COVID-19 has several metabolic and cardiopulmonary sequels, and at the same time, aggravates depression and dementia.
