Discrepancy between Physical Functional Decline and Physical Concerns among Alzheimer’s Disease

doi:10.21203/rs.3.rs-4185867/v1

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Discrepancy between Physical Functional Decline and Physical Concerns among Alzheimer’s Disease

https://doi.org/10.21203/rs.3.rs-4185867/v1

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Purpose

To examine the extent to which patients with amnestic mild cognitive impairment (aMCI) or Alzheimer’s disease (AD) perceive their own physical decline.

Methods

This study included 4585 outpatients (1036 normal cognition, 1712 aMCI, and 1837 mild AD) who visited a memory clinic. The patients and their families were asked about fear of falling, dizziness or unsteadiness, knee pain, and visual and hearing impairment. Logistic regression analysis was performed to examine the relationship between physical concerns and AD stage. The proportion of patients who had physical functional decline without physical concerns was also calculated according to Mini-Mental State Examination (MMSE) score.

Results

The number of physical concerns decreased from the aMCI stage, but actual physical function declined. The proportion of patients who had impaired physical function but no physical concerns increased as MMSE score decreased.

Conclusion

There was a discrepancy between physical concerns and physical functional decline among AD patients.

physical function

Alzheimer’s disease

amnestic mild cognitive impairment

compliments

Aim: This study examines the extent to which patients with amnestic mild cognitive impairment or Alzheimer’s disease perceive their own physical decline.

Findings: There was a discrepancy between physical concerns and physical functional decline in Alzheimer’s disease but not amnestic mild cognitive impairment.

Message: Asking outpatients at memory clinic about physical concerns is not enough to detect their physical functional decline.

As Alzheimer’s disease (AD) progresses, physical function decreases, accompanied by sensory impairment and orthopedic disease. In addition to physical functional decline, various factors such as central and peripheral sensory impairment, pain, sarcopenia, and mental problems can lead to concerns such as fear of falling (FOF) or dizziness.[1] These not only are associated with increased risk of falling but also result in restriction and avoidance of activities, ultimately impairing quality of life (QOL).[1] In the management of patients with amnestic mild cognitive impairment (aMCI) or AD, however, these concerns are challenging for health care providers, because it is unclear the extent to which patients with MCI or mild AD objectively perceive their decline in physical function.

Combined with decreased physical function and increased joint pain, declines in vestibular function, executive function, and visuospatial cognitive ability lead to increased risk of falling. Given this background, do concerns about FOF and dizziness increase as AD progresses with physical function declines? Contrary to expectations, individuals with AD are reported to have a lower prevalence of FOF compared to those with MCI and healthy controls. However, it has been reported that FOF is more prevalent in individuals with MCI than in those with normal cognition (NC).[2] Another study reported that there was no significant difference in the prevalence of FOF between individuals with NC and those with AD.[3] Studies in which MCI was subdivided showed that MCI due to dementia with Lewy bodies has a higher prevalence of FOF in comparison with NC or MCI due to AD.[4] Thus, the reported rate of FOF or dizziness in the course of AD is not consistent. The reason for this might be that the sample sizes in previous studies were too small or that the background type of MCI was not diagnosed in detail. On the other hand, evidence is mounting that, along with hearing loss, vestibular disorders could also be a significant risk factor for the development of cognitive dysfunction and dementia.[5] However, it is unclear what proportion of MCI or AD patients have concerns about dizziness.

In this study, we sought to examine how patients' physical concerns including FOF and dizziness differ between NC, aMCI, and mild AD, and to determine the extent to which the patients' physical concerns reliably reflected their physical function in the memory clinic setting. We also analyzed concerns about memory, pain and sensory disorders as factors involved in FOF and falls.[6–8]

A total of 4585 Japanese patients [1036 with NC, 1712 with aMCI, and 1837 with mild AD (MMSE ≥ 19)] aged 65 years or older attended an initial visit at our memory clinic at the National Center for Geriatrics and Gerontology from July 2010 to June 2021. All patients were diagnosed based on detailed neuropsychological tests and examinations as described in our previous report.[9]

The patients and their families were interviewed about their concerns related to physical function. In particular, we checked whether the following items from the Fall Risk Index [8] applied to the patients: fear of falling, dizziness or staggering, pain in the knees, vision difficulties, and hearing difficulties. Fear of forgetfulness was also investigated. Patients with Geriatric Depression Scale 15 (GDS) ≥ 5 were classified as having depressed mood.

Locomotion was assessed using Timed Up and Go (TUG) [10], and one leg standing (OLS) tests. TUG ≥ 11 s and OLS < 15 s [11]considered to indicate poor physical function. Low handgrip strength (GS) was defined as < 28 kg for men and < 18 kg for women.[12]

The Kruskal-Wallis test and Chi-square test were used to compare patient characteristics among the NC, aMCI, mild AD groups. Logistic regression analysis was also performed to examine the correlations of physical concerns and mental status with AD stage. Age, sex, years of education, number of comorbidities, GDS score, fall history in the past year (yes or no), and Dementia Behavior Disturbance Scale were included as covariates in the analysis. The fall history and Dementia Behavior Disturbance Scale were determined by interviewing the family. Statistical analysis was performed using SPSS software (ver. 29.0, SPSS, Chicago). A p-value of less than 0.05 was considered statistically significant. To examine whether there was a discrepancy between patients’ concerns and actual physical function, we determined the percentage of patients who had no concerns for any item but had TUG ≥ 11 s, OLS < 15, or low GS according to MMSE from 19 up to 30. Logistic and linear regression models were used to test for trends. This study received research ethics committee approval of the National Center for Geriatrics and Gerontology.

The percentage of patients with knee pain, visual impairment, and/or hearing impairment decreased with AD stage (p-trend < 0.01). Conversely, the proportion of patients with FOF, fear of forgetting, and GDS ≥ 5 increased with AD stage (p-trend < 0.01). There was no significant difference in dizziness and unsteadiness between the groups. Physical functional decline was seen for all items from the aMCI stage to the mild AD stage. (Table 1)

Table 1
		Normal cognition		aMCI		Mild AD
	N	Mean (SD)	N	Mean (SD)	N	Mean (SD)	P for trend
Age, years	1036	74.5 (5.7)	1712	77.7 (5.8)	1837	79.0 (5.8)	< 0.001
Men, n (%)	1036	447 (43.1)	1710	695 (40.6)	1834	581 (31.7)	< 0.001
Education years, years	1019	12.2 (2.6)	1688	11.1 (2.5)	1813	11.3 (28.4)	0.3
Number of Comorbidities	1036	1.1 (1.1)	1712	1.1 (1.2)	1837	1.1 (1.1)	0.9
Geriatric Depression scale	998	3.4 (2.9)	1654	3.4 (2.9)	1795	3.8 (2.9)	< 0.001
Falling history	1036	318 (30.7)	1712	502 (29.3)	1837	649 (35.3)	0.003
Dementia Behavior Disturbance Scale	954	6.3 (6.7)	1636	9.8 (8.0)	1784	15.3 (10.0)	< 0.001
Activities of Daily Living
Barthel Index ≤ 80%, n (%)	964	21 (2.2)	1643	49 (3.0)	1792	97 (5.4)	< 0.001
IADL ≤ 80%, n (%)	962	125 (13.0)	1645	516 (31.4)	1789	1159 (64.8)	< 0.001
Need assistance to go out, n (%)	956	7 (0.7)	1638	29 (1.8)	1783	76 (4.3)	< 0.001
Cognition
MMSE	1010	28.0 (4.6)	1684	24.3 (10.8)	1837	21.9 (5.6)	< 0.001
Compliments
Fear of falling, n (%)	992	357 (36.0)	1645	658 (40.0)	1774	836 (47.1)	< 0.001
Dizziness/ staggering, n (%)	992	287 (28.9)	1643	436 (26.5)	1774	485 (27.3)	0.5
Knee pain complain, n (%)	992	437 (44.1)	1643	615 (37.4)	1773	664 (37.5)	0.002
Vision impairment, n (%)	992	565 (57.0)	1644	858 (52.2)	1772	870 (49.1)	< 0.001
Hearing impairment, n (%)	988	611 (61.8)	1640	833 (50.8)	1772	872 (49.2)	< 0.001
Fear of forgetting, n (%)	993	836 (84.2)	1644	1513 (92.0)	1775	1692 (95.3)	< 0.001
GDS ≥ 5, n (%)	998	282 (28.3)	1654	446 (27.0)	1795	594 (33.1)	< 0.001
Physical function
U༆G ≥ 11sec, n (%)	953	339 (35.6)	1519	747 (49.2)	1614	917 (56.8)	< 0.001
OLS < 15sec, n (%)	867	432 (49.8)	1301	848 (65.2)	1345	961 (71.4)	< 0.001
Weak grip strength, n (%)	731	298 (40.8)	1153	642 (55.7)	1117	720 (64.5)	< 0.001
Data area presented as number (%) or mean (SD).

As shown in Table 2, after adjusting for covariates, compared with the NC group, both the aMCI and mild AD groups had significantly lower concerns about FOF, dizziness/unsteadiness, knee pain, visual impairment, and hearing impairment compared with the NC group. However, the aMCI group and mild AD group were more likely to have fear of forgetting. The prevalence of GDS ≥ 5 did not change in either the aMCI or AD group after adjustment for covariates.

Table 2

Odds ratios for patient concerns and physical function in comparison with the normal cognitional group by logistic regression
Independent Outcomes		Amnestic MCI		Mild Alzheimer’s disease
Independent Outcomes	N	B	OR (95%CI)	B	OR (95%CI)	p-trend
Physical concerns and mental status
Fear of falling ^a	4300	-0.3	0.8 (0.6–0.9)**	-0.4	0.6 (0.5–0.8)**	< 0.001
Dizziness/staggering ^a	4298	-0.3	0.8 (0.6–0.9)**	-0.5	0.6 (0.5–0.8)**	< 0.001
Knee pain ^a	4300	-0.5	0.6 (0.5–0.7)**	-0.7	0.5 (0.4–0.6)**	< 0.001
Visual impairment ^a	4299	-0.3	0.7 (0.6–0.9)**	-0.7	0.5 (0.4–0.6)**	< 0.001
Hearing impairment ^a	4289	-0.7	0.5 (0.4–0.6)**	-1.0	0.4 (0.3–0.5)**	< 0.001
Fear of forgetting ^a	4301	0.8	2.1 (1.6–2.8)**	0.9	2.5 (1.8–3.5)**	< 0.001
Geriatric Depression Scale ≥ 5 ^b	4339	-0.2	0.9 (0.7–1.1)	-0.02	1.0(0.8–1.2)	0.96
Physical function
Timed up and go ≥ 11 s ^a	3996	0.3	1.3 (1.1–1.6)**	0.4	1.5 (1.2–1.8)**	< 0.001
One-leg standing test < 15 s ^a	3435	0.2	1.3 (1.0-1.6)*	0.3	1.4 (1.1–1.7)**	0.02
Low grip strength ^a	2935	0.3	1.3 (1.1–1.6)**	0.4	1.5 (1.2–1.9)**	0.001
< 0.05 *< 0.01
^aAdjusted for age, sex, years of education, number of comorbidities, Geriatric depression scale 15, falling history, and Dementia Behavior Disturbance Scale.
^bAdjusted for age, sex, years of education, number of comorbidities, and Dementia Behavior Disturbance Scale.

Next, as shown in Fig. 1, among the patients with MMSE 30, 26.7% who had no concern about FOF and 28.6% who had no concern about dizziness/unsteadiness took more than 11 s for TUG measurement. With decreasing MMSE, the percentage of patients with TUG ≥ 11 s out of those without FOF (p-trend < 0.01) and those without dizziness or unsteadiness (p-trend < 0.01) increased. Similarly, with decreasing MMSE, the percentage of patients with OLS < 15 s (p-trend = 0.03) and low grip strength (p-trend = 0.04) out of those with no concern about dizziness increased. Although there was no significant trend of false negatives in the remaining items, more than half of those who answered that they had no FOF or dizziness had OLS < 15 s. Similarly, more than half of those who had no concerns about dizziness had low GS regardless of MMSE score.

The present results suggest that the physical concerns of memory clinic patients decreased significantly from the aMCI stage onward, though their actual physical function declined. As the MMSE scores decreased, the proportion of patients answering “no” to items about physical concerns increased, but more of these patients had slow walking speed and poor balance.

Our results are consistent with some previous studies. A previous cross-sectional study reported that cognitive impairment was significantly associated with absence of fear in falling in community-dwelling older individuals, which indicated that worse cognitive function may inhibit FOF. [13] Henry et al. found that patients with mild dementia had difficulty in differentiating between high- and low-danger situations, and this difficulty was related to more general cognitive decline.[14] Such difficulty can also result from sensory and pain concerns. Lack of FOF and poor perception of surrounding hazards could lead to subsequent falls. The physical functioning of these patients should be determined accurately.

Without adjusting covariates, the percentage of patients with FOF increased with cognitive decline, but the percentage with dizziness or unsteadiness did not change with AD stage. However, the results has changed after adjusting for covariates. This indicates many covariates such as their mood and BPSD are involved in the relationship between FOF or dizziness/unsteadiness and AD stages.

This study demonstrated that simply asking outpatients at memory clinic about physical and sensory concerns is not sufficient to detect their physical functional decline and sensory impairments. This suggests a need for objective assessment of physical and sensory functional decline, because such decline is directly related to activities of daily living. On the other hand, the percentage of patients with concerns about forgetfulness significantly increased from the aMCI stage. This was perhaps because the patients were visiting a memory clinic where patients’ main concerns are forgetfulness and related symptoms.

This study has some limitations. First, we did not use the Activities-specific Balance Confidence scale or Falls Efficacy Scale-International, which objectively indicate FOF. Similarly, no objective assessment of dizziness was used. In addition, we did not evaluate orthopedic conditions such as osteoarthritis or objectively assess hearing and vision except for physical function. Lastly, the study population was a relatively healthy group of patients with aMCI and mild AD who were physically and mentally able to visit an outpatient clinic after excluding patients with conditions such as dementia with Lewy bodies and vascular dementia, so it is not clear whether the results can be applied to all patients with dementia.

A discrepancy between the physical concerns and the actual degree of physical functional decline began from the aMCI stage and was present in mild AD.

Conflict of Interest

None.

Data Sharing

Raw data were generated at National Center for Geriatrics and Gerontology. Derived data supporting the findings of this study are available from the corresponding author on request.

Authors contributions

C.F. conceived of the study. C.F. and T.S developed the theory and performed the computations. C.F. and T.Sakurai. verified the analytical methods. H.U., H.N, H.K., K.W., M.N, Y.Y., T.T., T.Sakai, T.Sakurai. assisted C.F. in the data analysis and supervised the findings of this work. All authors discussed the results and contributed to the final manuscript.

Acknowledgements

This study was partially supported by Grants from the Chukyo Longevity Foundation and Research Funding for Longevity Sciences (30 − 1) from Japan’s National Center for Geriatrics and Gerontology. The funding sources were not involved in the study design, collection, analysis, interpretation of data, or writing of the paper.

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Discrepancy between Physical Functional Decline and Physical Concerns among Alzheimer’s Disease

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