帕金森病患者营养状况及其与认知功能的相关性

李晶, 卞来芳, 沈骏, 姜宇, 周仁华

新医学 ›› 2025, Vol. 56 ›› Issue (3) : 283-288.

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新医学 ›› 2025, Vol. 56 ›› Issue (3) : 283-288. DOI: 10.12464/j.issn.0253-9802.2024-0345
论著

帕金森病患者营养状况及其与认知功能的相关性

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Nutritional status and its correlation with cognitive function in patients with Parkinson’s disease

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摘要

目的 探讨帕金森病(PD)患者营养不良风险的发生情况,以及高营养不良风险与认知障碍的发生是否存在相关性。方法 纳入2023年3月至2025年1月泰州市第四人民医院收入的150例PD患者,采用老年营养风险指数(GNRI)评估PD患者的营养状况,GNRI评分≥98分表示不存在营养不良风险,评分< 98分表示高营养不良风险。将150例患者分为高GNRI组(评分≥98分)和低GNRI组(评分< 98分),采用简易精神状态量表(MMSE)对2组PD患者进行认知功能评估,分析认知障碍的患病率。采用Logistic回归分析营养不良风险与认知障碍的相关性。结果 150例PD患者中存在高营养不良风险的患者共70例,高营养不良风险发生率为46.7%。低GNRI组70例,高GNRI组80例,合并认知障碍患者共71例,患病率为47.3%,其中低GNRI组43例发生认知障碍,发病率为61.4%,MMSE评分为21.5(14.0,26.0)分,高GNRI组发生认知障碍者有28例,发病率为35.0%,MMSE评分为23.5(18.8,27.0)分,2组患者的认知障碍发生率、MMSE评分对比差异有统计学意义(均P < 0.05)。同时,2组患者的年龄、发病时间、H-Y分级、甘油三酯、甲状腺功能、血红蛋白、血糖、尿酸比较差异均有统计学意义(均P < 0.05),在血管危险因素、文化程度等方面比较差异无统计学意义(均P > 0.05)。多因素二元Logistic回归分析显示,在校正了疾病病程、H-Y分级等因素后,存在认知障碍(OR=2.66,P = 0.009)、年龄(OR=0.93,P = 0.004)、促甲状腺激素(OR=1.36,P = 0.006)是PD患者发生营养不良风险的影响因素。结论 PD患者发生营养不良风险高,有营养不良风险的PD患者认知障碍的发病率更高,存在认知障碍是PD患者发生高营养不良风险的危险因素。

Abstract

Objective To investigate the prevalence of malnutrition risk in patients with Parkinson’s disease (PD), and explore the correlation between high malnutrition risk and cognitive impairment. Methods A total of 150 PD patients admitted to the Forth People’s Hospital of Taizhou from March 2023 to January 2025 were included. The GeriatricNutritional Risk Index (GNRI) was used to assess the nutritional status of PD patients. A GNRI score ≥98 indicated no malnutrition risk, while a score < 98 indicated malnutrition risk. The patients were divided into a high GNRI group (score ≥98) and a low GNRI group (score < 98). Cognitive function was evaluated using the Mini-Mental State Examination (MMSE), and the prevalence of cognitive impairment was analyzed. Logistic regression was used to analyze the correlation between malnutrition risk and cognitive impairment. Results Among the 150 patients, 70 were at risk of malnutrition, with a high malnutrition risk prevalence of 46.7%. The low GNRI group comprised 70 patients, while the high GNRI group comprised 80 patients. A total of 71 patients had cognitive impairment, with an incidence rate of 47.3%.In the low GNRI group, 43 patients had cognitive impairment, with an incidence rate of 61.4% and an MMSE score of 21.5 (14.0, 26.0). In the high GNRI group, 28 patients had cognitive impairment, with an incidence of 35.0% and an MMSE score of 23.5 (18.8, 27.0). The differences in the incidence of cognitive impairment and MMSE scores between the two groups were statistically significant (both P < 0.05). At the same time, significant differences were observed between the two groups in terms of age, disease duration, H-Y stage, triglyceride levels, thyroid function, hemoglobin , blood glucose, and uric acid levels (all P < 0.05), while there were no statistically significant differences in vascular risk factors or educational level (all P > 0.05). Multivariate binary logistic regression analysis suggested that cognitive impairment (OR=2.66,P = 0.009),age(OR=0.93, P = 0.004), TSH(OR=1.36,P =0.006) were influencing factors for malnutrition risk in PD patients after correcting factors such as disease duration and H-Y stage. Conclusions PD patients have a high risk of malnutrition, and those at risk of malnutrition exhibit a higher incidence of cognitive impairment. Cognitive impairment is a risk factor for high malnutrition risk in PD patients.

关键词

帕金森病 / 营养不良 / 老年营养风险指数 / 认知障碍

Key words

Parkinson’s disease / Malnutrition / Geriatric nutritional risk index / Cognitive impairment

引用本文

导出引用
李晶 , 卞来芳 , 沈骏 , 姜宇 , 周仁华. 帕金森病患者营养状况及其与认知功能的相关性[J]. 新医学, 2025, 56(3): 283-288 https://doi.org/10.12464/j.issn.0253-9802.2024-0345
LI Jing , BIAN Laifang , SHEN Jun , JIANG Yu , ZHOU Renhua. Nutritional status and its correlation with cognitive function in patients with Parkinson’s disease[J]. JOURNAL OF NEW MEDICINE, 2025, 56(3): 283-288 https://doi.org/10.12464/j.issn.0253-9802.2024-0345
帕金森病(Parkinson’s disease,PD)是第二大最常见的神经退行性疾病[1],在老年人群中的发病率仅次于阿尔茨海默病[2]。据预测,至2042年,中国人群PD患病率将达到904.08/100 000[3],在未来30年内全球PD患者的数量将翻倍,预计至2050年全球PD患者将超过1 200万例[4]。PD除了明确的运动症状外还伴有多种非运动症状,其中认知障碍是较常见的,认知功能恶化将严重影响患者生活质量。营养不良在老年人群中很常见,在PD患者中也很普遍。近期有研究指出,营养状况可能与PD认知功能存在相关性,营养不良可能加速PD患者认知功能的下降,从而影响患者的生存质量及预后。因此,了解PD合并症和营养状况之间的关系非常重要,进一步的研究可能有助于制定干预策略,改善患者临床症状,并且提高患者生活质量。然而,目前关于PD患者营养状况与认知功能相关性的研究并不充分。本研究旨在深入探讨PD患者的营养状况,并分析其与认知功能之间的相关性,揭示营养不良对PD患者认知功能的影响,有助于制定针对性的营养干预措施,以期为临床实践中PD的综合治疗特供科学依据。

1 对象与方法

1.1 研究对象

本研究纳入2023年3月至2025年1月期间就诊于泰州市第四人民医院并被确诊为PD的患者共150例,所有患者均符合《中国帕金森病治疗指南(第四版)》诊断标准[5]。排除标准:①已知病因的继发性帕金森综合征、PD叠加综合征;②合并肿瘤、消化系统疾病、自身免疫疾病、活动性感染、慢性肾功能不全、遵循特殊饮食习惯(如严格低碳水化合物、低糖、低盐、低蛋白、素食等)。本研究已通过泰州市第四人民医院伦理委员会审查(批件号:2024-EC/TZFH-051),且所有入组患者均签署知情同意书。本研究根据Logistic回归模型,自变量为年龄、是否存在认知障碍、病程、Hoehn-Yahr病情分级(H-Y分级)、TSH、T3,自变量数为6个,根据10EPV原则,每个自变量需要至少10个事件,因此总需求为60个事件,实际件数为70,样本量足够。

1.2 临床信息收集

收集研究对象的人口统计学资料,包括年龄、性别、身高、体质量、受教育年限等。同时收集患者的基线特征,包括高血压、糖尿病、冠状动脉粥样硬化性心脏病(冠心病)、吸烟、饮酒史。于患者入院第2天空腹状态下采集静脉血,采用溴甲酚绿法检测血清白蛋白水平,同时收集其他实验室检查结果,包括血脂、甲状腺功能、胆固醇等。

1.3 营养状况评估

使用老年营养风险指数(Geriatric Nutritional Risk Index,GNRI)评估PD患者营养状况,计算公式:Y=1.489X1+41.7X2/X3,式中Y为GRNI,X1为血清白蛋白(单位为g/L),X2为患者入院时体质量(单位为kg),X3为理想体质量(单位为kg)。理想体质量采用洛伦兹公式计算,男性适用的计算公式为Y=X-100-(X-150)/4,女性适用的计算公式为Y=X-100-(X-150)/2.5,式中Y为理想体质量(单位为kg),X为身高(单位为cm)。当实际体质量超过理想体质量时,实际体质量/理想体质量比值被认为是1,当实际体质量未超过理想体质量时,其比值为实际结果[6]。根据GNRI得分,将研究人群分为2组:低GNRI组(高营养风险者,其GNRI<98分)和高GNRI组(无营养风险者,其GNRI≥98分)[7]

1.4 认知功能评估

入组的PD患者由固定的且资质合格的医师进行认知评估。本研究采用简易精神状态量表(mini mental state examination,MMSE)评估患者整体认知功能[8-9]。该量表涵盖6个认知域,包括定向力(10分)、即刻回忆(3分)、计算和注意力(5分)、延迟回忆(3分)、语言能力(8分)、视觉空间(1分)。本研究中视觉空间归入语言能力中共9分,根据文化程度和MMSE总分筛选认知功能障碍患者,其中文盲低于18分、小学学历低于24分、初中及以上学历27分以下者被视为存在认知功能障碍。

1.5 统计学方法

采用R 4.0.3统计软件进行统计分析。连续(定量)数据使用Shapiro-Wilk正态性检验,符合正态分布的数据采用x¯±s表示,组间比较采用独立样本t检验;不符合正态分布的数据采用M(P25,P75)表示,组间比较采用Wilcoxon检验。分类(定性)数据采用n(%)表示,组间比较采用χ 2检验。双侧P < 0.05为差异有统计学意义。

2 结果

2.1 低GNRI组与高GRNI组帕金森病患者的一般资料比较

本研究共纳入150例PD患者,根据GNRI评分分为低GNRI组70例和高GNRI组80例,合并认知障碍71例,患病率为47.3%。单因素分析显示,与高GNRI组PD患者相比,低GNRI组PD患者年龄较大、病程更长、H-Y分级更高、MMSE评分更低(均P < 0.05),并且2组PD患者在游离三碘甲状腺原氨酸(free triiodothyronine,FT3)、游离甲状腺素(free tetraiodothyronine,FT4)、三碘甲状腺原氨酸(triiodothyronine,T3)、促甲状腺激素(thyroid stimulating hormone,TSH)、甘油三酯、血红蛋白、血糖比较差异均有统计学意义(均P < 0.05),而2组PD患者在性别、高血压、糖尿病、冠心病、文化程度、总胆固醇水平、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇、甲状腺素(tetraiodothyronine,T4)等比较差异均无统计学意义(均P > 0.05),见表1
表1 低GNRI组与高GRNI组帕金森病患者的一般资料比较

Table 1 Comparison of general information between Parkinson, s disease patients with low GNRI and high GRNI

项 目 低GNRI组(n=70) 高GNRI组(n=80) χ 2/Z/t P
性别/n(%) 0.048 0.827
38(54.3) 42(52.5)
32(45.7) 38(47.5)
年龄/岁 76.0(72.0,79.0) 72.0(67.0,76.0) 3.714 <0.001
身高/cm 160.0(157.3,170.0) 163.5(158.0,169.0) -0.590 0.555
体质量/kg 59.19±10.31 64.39±8.43 -3.358 0.001
文化程度/n(%) 1.655 0.437
文盲 22(31.4) 33(41.3)
小学 22(31.4) 20(25.0)
初中及以上 26(37.1) 27(33.8)
病程/年 3.0(2.0,6.0) 2.0(1.0,5.0) 2.528 0.011
H-Y分级 3.0(2.5,4.0) 3.0(1.9,3.6) 2.292 0.022
PD治疗方案/n(%) 1.219 0.544
多巴制剂/多巴脱羧酶+激动剂 50(71.4) 61(76.3)
多巴制剂/多巴脱羧酶+激动剂+金刚烷胺 17(24.3) 14(17.5)
其他(单药、联合苯海索) 3(4.3) 5(6.3)
是否存在认知障碍/n(%) 10.460 0.001
43(61.4) 28(35.0)
27(38.6) 52(65.0)
MMSE/分 21.5(14.0,26.0) 23.5(18.8,27.0) -2.155 0.031
GNRI/分 93.1(89.8,95.6) 102.2(100.7,104.8) -10.496 <0.001
高血压/n(%) 0.964 0.326
38(54.3) 37(46.3)
32(45.7) 43(53.8)
糖尿病/n(%) 0.049 0.825
57(81.4) 64(80.0)
13(18.6) 16(20.0)
冠心病/n(%) 3.621 0.057
54(77.1) 71(88.8)
16(22.9) 9(11.2)
血红蛋白/(g/L) 118.9±15.5 129.8±14.0 -4.532 <0.001
FT3/(pmol/L) 4.2(3.7,4.6) 4.6(4.1,5.2) -3.524 <0.001
FT4/(pmol/L) 12.0(11.0,12.8) 11.3(10.0,12.5) 2.505 0.012
T3/(nmol/L) 1.25(1.01,1.39) 1.4(1.23,1.58) -3.553 <0.001
T4/(nmol/L) 119.0±21.2 123.6±22.2 -1.297 0.197
TSH/(mU/L) 1.57(1.11,2.86) 2.60(1.55,3.77) -2.867 0.004
低密度脂蛋白胆固醇/(mmol/L) 2.46±0.71 2.52±0.76 -0.551 0.583
高密度脂蛋白胆固醇/(mmol/L) 1.11(0.97,1.27) 1.20(1.05,1.38) -1.586 0.113
总胆固醇/(mmol/L) 4.0±0.9 4.2±1.1 -0.837 0.404
甘油三酯/(mmol/L) 0.97(0.82,1.35) 1.21(0.91,1.83) -2.579 0.010
血糖/(mmol/L) 5.0(4.6,5.5) 5.3(4.9,5.8) -2.185 0.029
血尿酸/(mmol/L) 299.5(236.3,363.5) 332.5(278.8,398.8) -1.999 0.046

2.2 帕金森病患者营养风险的多因素二元Logistic回归分析

应用R语言glm函数进行二元Logistic回归分析,因变量为有无营养风险,自变量为分类变量时,以最小值组作为参照组;自变量为连续变量时,直接将连续变量纳入二元Logistic回归模型。考虑到甲状腺功能可能与营养状况存在相关性,故补充自变量TSH、T3(因基线比较时TSH、FT3、FT4、T3两组间有统计学意义,但考虑到它们之间可能存在共线关系,因此最终纳入TSH、T3)。在校正了病程、H-Y分级等混杂因素后,存在认知障碍(OR=2.66,P = 0.009)、年龄(OR=0.93,P =0.004)、TSH(OR=1.36,P = 0.006)是PD患者发生营养不良风险的危险因素,见表2
表2 帕金森病患者营养风险的多因素二元Logistic回归分析

Table 2 Multivariate binary logistic regression analysis of nutritional risk in Parkinson, s disease patients

自变量 β β值标准误 Z P OR(95%CI)
常量 3.671 1.896 1.936 0.053
年龄 -0.068 0.023 -2.918 0.004 0.93(0.89,0.98)
是否存在认知障碍 0.980 0.374 2.623 0.009 2.66(1.28,5.54)
病程 -0.042 0.059 -0.715 0.475 0.96(0.86,1.08)
H-Y分级 -0.163 0.211 -0.771 0.441 0.85(0.56,1.29)
T3 -0.170 0.197 -0.862 0.389 0.84(0.57,1.24)
TSH 0.307 0.111 2.772 0.006 1.36(1.09,1.69)

3 讨论

营养是疾病管理中经常被忽视但又很重要的因素,营养不良是由于身体所需的能量、蛋白质及其他营养物质摄入不足和吸收不平衡或吸收不良所导致[10-11]。营养不良会对疾病的预后产生负面影响,并导致生活质量的下降。既往流行病学研究报道的PD患者营养不良患病率差异较大,而2022年的一项荟萃分析指出,PD患者营养不良及营养不良风险的患病率分别为8.8%和35.3%[12]。不同研究患病率的差异主要归因于评估营养状态的方法众多且定义营养不良的标准不一。目前,评估营养状态的工具通常包括人体测量参数、评估量表、血液生化指标等,但各自存在一定的局限性。一种新型简易营养评估工具——GNRI已被用于筛查各种疾病的营养不良或者营养不良风险,在评估疾病预后方面显示出良好的前景。GNRI是一种易于获得且无创的营养筛查工具,最初被引入并用于评估康复护理机构老年内科患者的营养状况[13]。已有研究提示,GNRI在PD患者的营养风险评估中具有一定应用价值[14]。因此,本研究采用GNRI评估PD患者的营养状况。本研究结果显示,150例PD患者中70例存在营养不良风险,占比为46.7%。与高GNRI组相比,低GNRI组患者年龄更大、病程更长、H-Y分级更高,血红蛋白、甘油三酯、FT3、血糖、血尿酸水平更低,提示年龄大、病程长、H-Y分级高与高营养不良风险可能相关,而低水平的血红蛋白、甘油三酯、FT3、血糖、血尿酸也可能是营养不良风险导致的结果。
在PD发生及发展的过程中,疾病本身及治疗PD药物的不良反应均可能导致患者出现营养问题。PD症状(包括胃肠道和非胃肠道症状)会对营养状况产生不利影响。PD患者的临床症状如肢体震颤、肌肉强直可增加机体的消耗[2],自主神经功能紊乱可导致胃肠功能紊乱、蠕动减少、便秘等[15-16],晚期的吞咽困难、饮水呛咳等问题可导致患者的饮食及营养问题[17-18]。嗅觉丧失是PD中常见的症状,嗅觉和味觉的下降会对营养状况产生负面影响[19-20]。另外,PD的治疗方法也可能增加营养不良风险,因治疗PD的药物几乎都具有不同程度的消化与吸收相关的不良反应,可能导致胃肠道反应,也可能影响对新陈代谢至关重要的营养物质处理而引起营养不良[21-22]。上述因素均会对PD患者的营养状况产生不利影响。
既往有研究指出,PD患者认知障碍的发病率是健康人群的3~6倍[23]。本研究显示,150例PD患者中发生认知障碍71例,占比为47.3%,与无营养不良风险患者相比,高营养不良风险的PD患者认知障碍发生率更高、MMSE评分更低。Logistic回归分析显示,在校正了发病年数、H-Y分级等混杂因素后,存在认知障碍是PD患者发生营养不良风险的独立危险因素。认知障碍是PD自然史的一部分,可发生在疾病的任何阶段,甚至可在PD的早期阶段出现[24]。营养不良可加重PD患者的失能和失忆、感觉缺陷等症状,进而导致患者认知功能下降[25]。而当PD患者出现认知障碍,尤其是痴呆后,其进食的主动性下降、饮食习惯改变等情况可进一步加重营养不良,从而形成营养不良-认知障碍-营养不良加重的恶性循环。
笔者认为,营养不良对PD认知功能的影响有以下几种潜在的机制:①PD患者的运动症状及非运动症状可能会导致食物摄入量减少,引起胃饥饿素分泌增加,胃饥饿素可进入中枢神经系统,作用于海马中的生长激素受体,从而影响认知功能;②营养不良可能导致大脑所必需的营养物质的缺乏,而影响神经细胞的生长、修复及功能发挥;③营养不良可能引起脑内能量代谢障碍,最终导致认知功能下降[26]
目前大部分研究者认为,部分饮食模式如地中海、营养补充剂、益生菌和生酮饮食等可能对PD患者有保护作用[27-28],但仍需更多的研究来探讨特定饮食模式对PD的影响。
综上所述,PD患者发生营养不良风险高,且有营养不良风险的PD患者认知障碍发病率更高,认知水平更低。GNRI评分作为营养不良风险的筛查工具,是根据患者血清白蛋白水平及机体指标进行营养状况的评估,客观且易操作,易于推广。但本研究也存在一些局限性,首先,本次研究纳入的样本量较小。其次,患者营养评估体现的是住院时的营养状态,未能动态监控PD患者病程中的营养状态变化。未来研究者可增加样本量及增加随访研究,深入研究营养干预对PD患者认知功能的影响,进一步明确营养不良与认知障碍的关系及发病机制,为临床医师对PD患者进行营养评估、制定个体化营养干预提供理论依据,可能有助于减少PD患者认知障碍的发生,从而改善PD患者的生存质量,延长生存时间。
利益冲突声明:本研究未受到企业、公司等第三方资助,不存在潜在利益冲突。

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江苏省老年健康科研项目(LSD2022038)
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