{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:59:39Z","timestamp":1787029179045,"version":"build-2736575974"},"reference-count":48,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2018,5,3]],"date-time":"2018-05-03T00:00:00Z","timestamp":1525305600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Abnormalities of water homeostasis can be early expressions of neuronal dysfunction, brain atrophy, chronic cerebrovasculopathy and neurodegenerative disease. The aim of this study was to analyze the serum osmolality of subjects with cognitive impairment. One thousand and ninety-one consecutive patients attending the Alzheimer\u2019s Evaluation Unit were evaluated with the Mini-Mental State Examination (MMSE), 21-Item Hamilton Depression Rating Scale (HDRS-21), Activities of Daily Living (ADL), Instrumental-ADL (IADL), Mini Nutritional Assessment (MNA), Exton-Smith Scale (ESS), and Cumulative Illness Rating Scale (CIRS). For each patient, the equation for serum osmolality developed by Khajuria and Krahn was applied. Five hundred and seventy-one patients had cognitive decline and\/or depression mood (CD-DM) and 520 did not have CD-DM (control group). Patients with CD-DM were less likely to be male (p &lt; 0.001), and were more likely to be older (p &lt; 0.001), have a significant clear cognitive impairment (MMSE: p &lt; 0.001), show the presence of a depressive mood (HDRS-21: p &lt; 0.001) and have major impairments in ADL (p &lt; 0.001), IADL (p &lt; 0.001), MNA (p &lt; 0.001), and ESS (p &lt; 0.001), compared to the control group. CD-DM patients had a higher electrolyte concentration (Na+: p &lt; 0.001; K+: p &lt; 0.001; Cl\u2212: p &lt; 0.001), risk of dehydration (osmolality p &lt; 0.001), and kidney damage (eGFR: p = 0.021), than the control group. Alzheimer\u2019s disease (AD) patients showed a major risk for current dehydration (p \u2264 0.001), and dehydration was associated with the risk of developing a type of dementia, like AD or vascular dementia (VaD) (OR = 2.016, p &lt; 0.001). In the multivariate analysis, the presence of dehydration state was associated with ADL (p &lt; 0.001) and IADL (p &lt; 0.001), but independently associated with age (r2 = 0.0046, p = 0.77), ESS (r2 = 0.0052, p = 0.54) and MNA (r2 = 0.0004, p = 0.48). Moreover, younger patients with dementia were significantly more dehydrated than patients without dementia (65\u201375 years, p = 0.001; 76\u201385 years, p = 0.001; \u226586 years, p = 0.293). The hydromolecular hypothesis intends to explain the relationship between dehydration and cognitive impairment in older patients as the result of protein misfolding and aggregation, in the presence of a low interstitial fluid volume, which is a defect of the microcirculation. Defective proteins were shown to impair the amount of information in brain biomolecular mechanisms, with consequent neuronal and synaptic damage.<\/jats:p>","DOI":"10.3390\/nu10050562","type":"journal-article","created":{"date-parts":[[2018,5,3]],"date-time":"2018-05-03T03:20:27Z","timestamp":1525317627000},"page":"562","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":52,"title":["Neurocognitive Disorders and Dehydration in Older Patients: Clinical Experience Supports the Hydromolecular Hypothesis of Dementia"],"prefix":"10.3390","volume":"10","author":[{"given":"Michele","family":"Lauriola","sequence":"first","affiliation":[{"name":"Complex Structure of Geriatrics, Department of Medical Sciences, IRCCS \u201cCasa Sollievo della Sofferenza\u201d, San Giovanni Rotondo, Viale Cappuccini 1, 71013 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Mangiacotti","sequence":"additional","affiliation":[{"name":"Complex Structure of Geriatrics, Department of Medical Sciences, IRCCS \u201cCasa Sollievo della Sofferenza\u201d, San Giovanni Rotondo, Viale Cappuccini 1, 71013 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grazia","family":"D\u2019Onofrio","sequence":"additional","affiliation":[{"name":"Complex Structure of Geriatrics, Department of Medical Sciences, IRCCS \u201cCasa Sollievo della Sofferenza\u201d, San Giovanni Rotondo, Viale Cappuccini 1, 71013 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leandro","family":"Cascavilla","sequence":"additional","affiliation":[{"name":"Complex Structure of Geriatrics, Department of Medical Sciences, IRCCS \u201cCasa Sollievo della Sofferenza\u201d, San Giovanni Rotondo, Viale Cappuccini 1, 71013 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Paris","sequence":"additional","affiliation":[{"name":"Complex Structure of Geriatrics, Department of Medical Sciences, IRCCS \u201cCasa Sollievo della Sofferenza\u201d, San Giovanni Rotondo, Viale Cappuccini 1, 71013 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Paroni","sequence":"additional","affiliation":[{"name":"Complex Structure of Geriatrics, Department of Medical Sciences, IRCCS \u201cCasa Sollievo della Sofferenza\u201d, San Giovanni Rotondo, Viale Cappuccini 1, 71013 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Seripa","sequence":"additional","affiliation":[{"name":"Complex Structure of Geriatrics, Department of Medical Sciences, IRCCS \u201cCasa Sollievo della Sofferenza\u201d, San Giovanni Rotondo, Viale Cappuccini 1, 71013 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Greco","sequence":"additional","affiliation":[{"name":"Complex Structure of Geriatrics, Department of Medical Sciences, IRCCS \u201cCasa Sollievo della Sofferenza\u201d, San Giovanni Rotondo, Viale Cappuccini 1, 71013 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"Sancarlo","sequence":"additional","affiliation":[{"name":"Complex Structure of Geriatrics, Department of Medical Sciences, IRCCS \u201cCasa Sollievo della Sofferenza\u201d, San Giovanni Rotondo, Viale Cappuccini 1, 71013 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,5,3]]},"reference":[{"key":"ref_1","first-page":"172","article-title":"Thirst in older patients subjects","volume":"2","author":"Naitoh","year":"1998","journal-title":"J. Nutr. Health Aging"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1159\/000022063","article-title":"A review of water balance in ageing in health and disease","volume":"45","author":"Stout","year":"1999","journal-title":"Gerontology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1098\/rspb.1947.0037","article-title":"The antidiuretic hormone and the factors which determine its release","volume":"135","author":"Verney","year":"1947","journal-title":"Proc. R. Soc. Lond. B Biol. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.ecl.2013.02.005","article-title":"Age-Associated Abnormalities of Water Homeostasis","volume":"42","author":"Cowen","year":"2013","journal-title":"Endocrinol. Metab. Clin."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"852","DOI":"10.2215\/CJN.10741013","article-title":"Osmotic homeostasis","volume":"10","author":"Danziger","year":"2015","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_6","first-page":"26","article-title":"The aging kidney. Defending a delicate balance of fluid and electrolytes","volume":"55","author":"Beck","year":"2000","journal-title":"Geriatrics"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"768","DOI":"10.7326\/0003-4819-107-5-768","article-title":"Geriatric hypernatremia","volume":"107","author":"Beck","year":"1987","journal-title":"Ann. Intern. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1111\/j.1753-4887.1990.tb02915.x","article-title":"Aging and disturbances of thirst and fluid balance","volume":"48","author":"Rolls","year":"1990","journal-title":"Nutr. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"18","DOI":"10.3389\/fmolb.2016.00018","article-title":"Dehydration and Cognition in Geriatrics: A Hydromolecular Hypothesis","volume":"3","author":"Sfera","year":"2016","journal-title":"Front. Mol. Biosci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1016\/j.jalz.2014.01.001","article-title":"A conceptual framework for research on subjective cognitive decline in preclinical Alzheimer\u2019s disease","volume":"10","author":"Jessen","year":"2014","journal-title":"Alzheimers Dement."},{"key":"ref_11","unstructured":"(2013). American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, American Psychiatric Publishing. [5th ed.]."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.jalz.2011.03.008","article-title":"The diagnosis of mild cognitive impairment due to Alzheimer\u2019s disease: Recommendations from the National Institute on Aging-Alzheimer\u2019s Association workgroups on diagnostic guidelines for Alzheimer\u2019s disease","volume":"7","author":"Albert","year":"2011","journal-title":"Alzheimers Dement."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.jalz.2011.03.005","article-title":"The diagnosis of dementia due to Alzheimer\u2019s disease: Recommendations from the National Institute on Aging-Alzheimer\u2019s Association workgroups on diagnostic guidelines for Alzheimer\u2019s disease","volume":"7","author":"McKhann","year":"2011","journal-title":"Alzheimers Dement."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1863","DOI":"10.1212\/01.wnl.0000187889.17253.b1","article-title":"Diagnosis and management of dementia with Lewy bodies: Third report of the DLB Consortium","volume":"65","author":"McKeith","year":"2005","journal-title":"Neurology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1212\/WNL.43.2.250","article-title":"Vascular dementia: Diagnostic criteria for research studies. Report of the NINDS-AIREN International Workshop","volume":"43","author":"Roman","year":"1993","journal-title":"Neurology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/0022-3956(75)90026-6","article-title":"Mini-mental state: A practical method for grading the cognitive state of patients for the clinician","volume":"12","author":"Folstein","year":"1975","journal-title":"J. Psychiatr. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1192\/bjp.140.6.566","article-title":"A new clinical scale for the staging of dementia","volume":"140","author":"Hughes","year":"1982","journal-title":"Br. J. Psychiatry"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1001\/archneur.1975.00490510088009","article-title":"Cerebral blood flow in dementia","volume":"32","author":"Hachinski","year":"1975","journal-title":"Arch. Neurol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1136\/jnnp.23.1.56","article-title":"A rating scale for depression","volume":"23","author":"Hamilton","year":"1960","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1093\/geront\/10.1_Part_1.20","article-title":"Progress in the development of an index of ADL","volume":"10","author":"Katz","year":"1970","journal-title":"Gerontologist"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1093\/geront\/9.3_Part_1.179","article-title":"Assessment of older people: Self-maintaining and instrumental activities of daily living","volume":"9","author":"Lawton","year":"1969","journal-title":"Gerontologist"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/S0899-9007(98)00171-3","article-title":"The Mini Nutritional Assessment (MNA) and its use in grading the nutritional state of older patients","volume":"15","author":"Vellas","year":"1999","journal-title":"Nutrition"},{"key":"ref_23","first-page":"238","article-title":"Mattresses for preventing pressure sores in geriatric patients","volume":"25","author":"Bliss","year":"1966","journal-title":"Mon. Bull. Minist. Health Public Health Lab. Serv."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1111\/j.1532-5415.1995.tb06377.x","article-title":"Validation of the Cumulative illness rating scale in a geriatric residential population","volume":"43","author":"Parmelee","year":"1995","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1055\/s-2004-821318","article-title":"The effects of dehydration on brain volume\u2014Preliminary results","volume":"26","author":"Dickson","year":"2005","journal-title":"Int. J. Sports Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"867","DOI":"10.3945\/ajcn.114.086769","article-title":"Accuracy of prediction equations for serum osmolarity in frail older people with and without diabetes","volume":"100","author":"Siervo","year":"2014","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"604","DOI":"10.7326\/0003-4819-150-9-200905050-00006","article-title":"A new equation to estimate glomerular filtration rate","volume":"150","author":"Levey","year":"2009","journal-title":"Ann. Intern. Med."},{"key":"ref_28","unstructured":"National Kidney Foundation (2002). K\/DOQI clinical practice guidelines for chronic kidney disease: Evaluation, classification, and stratification. Am. J. Kidney Dis., 39, S1\u2013S266."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1111\/j.1532-5415.1994.tb07488.x","article-title":"Arginine vasopressin and osmolarity in the older patients","volume":"42","author":"Johnson","year":"1994","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"4","DOI":"10.3928\/0098-9134-19900501-04","article-title":"A question of balance\u2014Dehydration in the older patients","volume":"16","author":"Kositzke","year":"1990","journal-title":"J. Gerontol. Nurs."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1016\/S0001-2092(07)63314-6","article-title":"Dehydration in the older patients surgical patient","volume":"60","author":"Martin","year":"1994","journal-title":"AORN J."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1841","DOI":"10.1017\/S0007114513004455","article-title":"Masento Effects of hydration status on cognitive performance and mood","volume":"111","author":"Natalie","year":"2014","journal-title":"Br. J. Nutr."},{"key":"ref_33","unstructured":"Food and Nutrition Board (2004). Dietary Reference Intakes for Water, Potassium, Sodium, Chloride, and Sulfate, The National Academies Press."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1678","DOI":"10.1016\/j.metabol.2009.06.022","article-title":"Hypovolaemia-induced obesity and diabetes","volume":"58","author":"Fetissov","year":"2009","journal-title":"Metab. Clin. Exp."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1038\/ijo.2008.264","article-title":"Hydration increases cell metabolism","volume":"33","author":"Thornton","year":"2009","journal-title":"Int. J. Obes."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"279","DOI":"10.3389\/fnagi.2014.00279","article-title":"Diabetes and hypertension, as well as obesity and Alzheimer\u2019s disease, are linked to hypohydration-induced lower brain volume","volume":"6","author":"Thornton","year":"2014","journal-title":"Front. Aging Neurosci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1111\/j.1532-5415.1983.tb05118.x","article-title":"Hypernatremic dehydration in nursing home patients: An indicator of neglect","volume":"31","author":"Himmelstein","year":"1983","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"S19","DOI":"10.1046\/j.1440-172X.2003.00425.x","article-title":"Maintaining oral hydration in older adults: A systematic review","volume":"9","author":"Hodgkinson","year":"2003","journal-title":"Int. J. Nurs. Pract."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1111\/j.1532-5415.1981.tb01761.x","article-title":"Hypernatremia in the older patients: Relation to infection and mortality","volume":"29","author":"Mahowald","year":"1981","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_40","unstructured":"Skipper, A. (1989). Dietitian\u2019s Handbook of Enteral and Parenteral Nutrition, Aspen Publishers."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"P321","DOI":"10.1093\/geronj\/47.5.P321","article-title":"Age-related changes in natural spontaneous fluid ingestion and thirst in humans","volume":"47","year":"1992","journal-title":"J. Gerontol."},{"key":"ref_42","unstructured":"Grant, A., and DeHoog, S. (1991). Nutritional Assessment and Support, Grant\/DeHoog. [4th ed.]."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.physbeh.2010.02.026","article-title":"Thirst and hydration: Physiology and consequences of dysfunction","volume":"100","author":"Thornton","year":"2010","journal-title":"Physiol. Behav."},{"key":"ref_44","unstructured":"Thornton, S.N., and Benetos, A. (2017, August 22). Dementia, Alzheimer\u2019s and Diabetes Could Be Linked through Hypovolaemia. Available online: http:\/\/n.neurology.org\/content\/dementia-alzheimers-and-diabetes-could-be-linked-through-hypovolaemia."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1046\/j.1523-1755.1999.00532.x","article-title":"Total body water data for white adults 18 to 64 years of age: The Fels Longitudinal Study","volume":"56","author":"Chumlea","year":"1999","journal-title":"Kidney Int."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1016\/j.clnu.2008.07.010","article-title":"Influence of gender and body composition on hydration and body water spaces","volume":"27","author":"Ritz","year":"2008","journal-title":"Clin. Nutr."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/S0074-7696(05)25005-2","article-title":"Cell volume and insulin signaling","volume":"225","author":"Schliess","year":"2003","journal-title":"Int. Rev. Cytol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1212\/01.WNL.0000150542.16969.CC","article-title":"Dehydration confounds the assessment of brain atrophy","volume":"64","author":"Duning","year":"2005","journal-title":"Neurology"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/10\/5\/562\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:03:02Z","timestamp":1760194982000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/10\/5\/562"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,5,3]]},"references-count":48,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2018,5]]}},"alternative-id":["nu10050562"],"URL":"https:\/\/doi.org\/10.3390\/nu10050562","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,5,3]]}}}