Type 3 diabetes

Last updated
Type 3 diabetes
Alzheimer's disease brain comparison.jpg
Diagram showing late stages of Alzheimer's disease in the brain caused by type 3 diabetes
Specialty Neurology
Symptoms Memory loss, linguistic problems, mood and behavioural swings and motivational loss
Usual onsetFrom early childhood/adolescence onward
DurationLong-term
Causes type 1 diabetes, type 2 diabetes
Risk factors Genetics and Lifestyle
Diagnostic method Based on symptoms and cognitive testing after ruling out other possible causes
PreventionDiet, physical and mental exercise, and psychological well-being
Medication Melatonin or Glucagon-like Peptide 1 Administration (small benefit)
FrequencyUnknown

Type 3 diabetes is a proposed pathological linkage between Alzheimer's disease and certain features of type 1 and type 2 diabetes. [1] Specifically, the term refers to a set of common biochemical and metabolic features seen in the brain in Alzheimer's disease, and in other tissues in diabetes; [1] [2] it may thus be considered a "brain-specific type of diabetes." [3] It was recognized at least as early as 2005 that some features of brain function in Alzheimer's disease mimic those that underlie diabetes. [4] However, the concept of type 3 diabetes is controversial, and as of 2021 it was not an officially recognized diagnosis. [5]

Contents

Metabolic risk factors such as hyperglycaemia, oxidative stress and lipid peroxidation are common processes thought to be contributors to the development of Alzheimer's disease in people with diabetes. [6] But while insulin resistance is a risk factor for the development of Alzheimer's disease and some other dementias, causes of Alzheimer's disease are likely to be much more complex than being explained by insulin factors on their own, and indeed several patients with Alzheimer's disease have normal insulin metabolism. [7]

The techniques used to prevent the disease in patients with diabetes are similar to individuals who do not show signs and symptoms of the disease. [8] The four pillars of Alzheimer's disease prevention [9] are currently used as a guide for individuals of who are at risk of developing Alzheimer's disease. As with Alzheimer's disease more broadly, there is no cure for type 3 diabetes, but disease progression may be slowed with certain drugs. [5]

Signs and symptoms

Alzheimer's disease is associated with a progressive decline in mental faculties. At early stages, forgetfulness, poor judgment, lack of awareness of date or location, and mood disturbances may be evident. This progresses to major difficulties in performing everyday tasks and recognizing familiar people. At later stages, the ability to speak is lost, and control of basic body functions is lost or greatly diminished. [10]

These symptoms may be exacerbated in individuals with pre-existing type 1 or type 2 diabetes. Individuals with type 1 diabetes are often diagnosed at a young age, usually between childhood and adolescence. [6] In some cases, brain development in these patients is negatively impacted, resulting in cognitive impairment earlier in life. [6] In type 2 diabetes, which is usually diagnosed later in life, patients often exhibit cognitive impairment that correlates with the length of time since initial type 2 diabetes onset, and with poor glycemic control. [6] [11] The observation that both types 1 and 2 diabetes can contribute to the development of Alzheimer's disease led to the hypothesis that Alzheimer's disease reflects a brain-specific "type 3" of diabetes. [11]

Cause

There are a number of mechanisms that attempt to explain the cause, progression and the link between type 1 diabetes, type 2 diabetes and Alzheimer's disease. [12] [6] [1] [13]

Insulin resistance

Insulin resistance is a reduction in the body's sensitivity to insulin, which is required for most cells to use glucose. Thus, in type 3 diabetes, the neurons lack sufficient glucose to function properly. This deficiency can lead to a decrease in memory, judgement and the ability to reason, which are key symptoms of Alzheimer's disease. [12]

Elevated cholesterol

Elevated serum cholesterol, specifically LDL cholesterol, is a risk factor for AD, [14] and a variant of the cholesterol transport protein apoE is the most common genetic risk factor for late-onset AD. [15] Treatment with statins, which inhibit cholesterol synthesis in the liver, has furthermore been shown to decrease risk for dementia of various types. [16] LDL cholesterol levels are also a known risk factor for type 2 diabetes, [17] and type 2 diabetes itself can lead to chemically-altered LDLs and an increased residence time of LDL cholesterol in the blood. [18]

Oxidative stress and lipid peroxidation

Hyperglycemia, which frequently occurs in diabetes, can lead to formation of advanced glycation end-products and reactive oxygen species (ROS) in the brain. [1] The resulting oxidative stress causes chemical changes in the protein and lipid molecules that are essential to brain function. [1] The brain, which contains a high proportion of polyunsaturated fatty acids and relatively low levels of antioxidant proteins like catalase and superoxide dismutase, [1] is especially sensitive to this oxidative stress. One of the main biomarkers of oxidative stress is lipid peroxidation, or the presence of reactive peroxide groups on fatty acid molecules. These peroxides disrupt the integrity of cell membranes, cause harmful chemical modifications of critial membrane proteins, and may lead to disorganization of microtubules, [19] contributing to dysfunction in brain cells.

Diagnosis

A minor to medium decline in cognitive function is found to be linked with both type 1 diabetes and type 2 diabetes. [1] However there are substantial variances in the cognitive pathophysiology of both type 1 diabetes and type 2 diabetes, leading to impairment. [20] Type 2 diabetes is characteristically diagnosed from within the late fifties to mid-sixties age range however it is possible to be diagnosed younger. [21] This form of diabetes is typically related to insulin resistance, dyslipidemia, hypertension and obesity. These mechanisms have a harmful influence on brain development. [10]

Type 1 diabetes is typically detected at a young age and may have negative impacts on cognitive growth. In both forms of diabetes, microvascular complications and hyperglycaemia are mutual risk factors that are found to contribute to the cognitive decline in patients. [10]

Prevention

There is no evidence today supporting a definitive method for preventing the onset of Alzheimer's disease in diabetic patients. However the four pillars of Alzheimer's prevention which outlines diet, physical and mental exercise, yoga and meditation and psychological well-being is recommended to patients who are at risk. [9] [22]

Diet

Mediterranean diet foods DIETA MEDITERRANEA ITALIA.JPG
Mediterranean diet foods

Mediterranean diet, a diet based around fruit, vegetables, olive oil, nuts and seafood has been shown to lower the risks of Alzheimer's disease in patients. [9] Specifically, patients who followed this diet which is modeled on particular Mediterranean nations presented decreasing amounts of amyloid-beta plaques between their nerve cells in the brain, [22] signifying the cell connections within the brain were firing correctly. This diet also presented increases in the thickness in the memory division of the brain cortex in the formal and parietal lobes and areas of cognition such as language and memory. [22] Updated versions of the Mediterranean diet such as the DASH diet have been recommended for patients, adding juicing and supplements to the recommendation for patients. [22]

Physical and mental exercise

Two people exercising Faversham 10K & 1.5K fun run 2015 FNK 0304 (20995354974).jpg
Two people exercising

Physical exercise increases the amount of blood flow through the brain while simultaneously causing the growth of brain cells known as neurogenesis. [9] [23] One hundred and twenty minutes of aerobic exercise and multiple strength training sessions per week are suggested to maintain and increase memory function in the patient. [24] Mental stimulation is also recommended for patients. [24] Brain aerobic activities such as reading and puzzles are endorsed to test and stimulate cognitive functioning while creative activities like painting and viewing art also activate the conditioning of the brain. [9] [22]

Yoga and meditation

Mediation and yoga have been found to reduce stress, which is a major element in the cause of Alzheimer's disease. [9] Stress has a negative impact on a patient's genes such as producing inflammation in the brain, a key component of Alzheimer's disease. [25] Simple twelve minute meditation each day reduces levels of stress in patients and extends the flow of blood to key areas of the brain responsible for memory performance. [9] [25] Yoga also stimulates the Anterior Cingulate Gyrus, a key area in the brain which manages memory recall, stress, emotive and cognitive stability.[ citation needed ]

Psychological well-being

Psychological well-being factors such as self-acceptance and confidence, personal growth, regular socialization and independence decrease the probability of mental decline and reduce inflammation within the brain. [26] Purpose in Life is now considered to increase the physiological health of patients with Alzheimer's disease. [9] Optimistic emotions such as love, appreciation and kindness are known to lessen the stress response and maintain a healthy cognition throughout the rest of the patient's life. [26]

Management

Melatonin administration

Chemical structure of Melatonin Melatonin.svg
Chemical structure of Melatonin

Melatonin is discharged by the pineal gland as a neurohormone. [3] Melatonin is a central hormone in the treatment of patients with Alzheimer's disease as it adjusts sleep patterns that are abnormal, which occurs in over forty five percent of patients. [3] [27]

Glucagon-like Peptide 1 administration

The administration of the hormone Glucagon-like Peptide 1 has shown to control the deregulation of glucose metabolism in patients with Alzheimer's disease. [28] This hormone can recover cerebral dysfunction in diabetes induced Alzheimer's disease. The hormone Glucagon-like Peptide 1 can lessen the brain's inflamed reaction caused by amyloid beta oxidative stress. [13] [28] Glucagon-like Peptide 1 can also increase the rate of neurogenesis within the brains of Alzheimer's patients. [13] Glucagon-like Peptide 1 has the possibility to increase the production of neurons to substitute impaired neurons within the brain. [13] This hormone can also decrease the brain's insulin resistance in Alzheimer's patients. [28]

Related Research Articles

<span class="mw-page-title-main">Dementia</span> Long-term brain disorders causing impaired memory, thinking and behavior

Dementia is the general name for a decline in cognitive abilities that impacts a person's ability to perform everyday activities. This typically involves problems with memory, thinking, and behavior. Aside from memory impairment and a disruption in thought patterns, the most common symptoms include emotional problems, difficulties with language, and decreased motivation. The symptoms may be described as occurring in a continuum over several stages. Dementia ultimately has a significant effect on the individual, caregivers, and on social relationships in general. A diagnosis of dementia requires the observation of a change from a person's usual mental functioning and a greater cognitive decline than what is caused by normal aging.

<span class="mw-page-title-main">Low-density lipoprotein</span> One of the five major groups of lipoprotein

Low-density lipoprotein (LDL) is one of the five major groups of lipoprotein that transport all fat molecules around the body in extracellular water. These groups, from least dense to most dense, are chylomicrons, very low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), low-density lipoprotein (LDL) and high-density lipoprotein (HDL). LDL delivers fat molecules to cells. LDL is involved in atherosclerosis, a process in which it is oxidized within the walls of arteries.

<span class="mw-page-title-main">Metabolic syndrome</span> Medical condition

Metabolic syndrome is a clustering of at least three of the following five medical conditions: abdominal obesity, high blood pressure, high blood sugar, high serum triglycerides, and low serum high-density lipoprotein (HDL).

<span class="mw-page-title-main">Abdominal obesity</span> Excess fat around the stomach and abdomen

Abdominal obesity, also known as central obesity and truncal obesity, is the human condition of an excessive concentration of visceral fat around the stomach and abdomen to such an extent that it is likely to harm its bearer's health. Abdominal obesity has been strongly linked to cardiovascular disease, Alzheimer's disease, and other metabolic and vascular diseases.

<span class="mw-page-title-main">Hyperglycemia</span> Too much blood sugar, usually because of diabetes

Hyperglycemia is a condition in which an excessive amount of glucose circulates in the blood plasma. This is generally a blood sugar level higher than 11.1 mmol/L (200 mg/dL), but symptoms may not start to become noticeable until even higher values such as 13.9–16.7 mmol/L (~250–300 mg/dL). A subject with a consistent fasting blood glucose range between ~5.6 and ~7 mmol/L is considered slightly hyperglycemic, and above 7 mmol/L is generally held to have diabetes. For diabetics, glucose levels that are considered to be too hyperglycemic can vary from person to person, mainly due to the person's renal threshold of glucose and overall glucose tolerance. On average, however, chronic levels above 10–12 mmol/L (180–216 mg/dL) can produce noticeable organ damage over time.

<span class="mw-page-title-main">Type 2 diabetes</span> Type of diabetes mellitus with high blood sugar and insulin resistance

Type 2 diabetes (T2D), formerly known as adult-onset diabetes, is a form of diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. Common symptoms include increased thirst, frequent urination, fatigue and unexplained weight loss. Symptoms may also include increased hunger, having a sensation of pins and needles, and sores (wounds) that do not heal. Often symptoms come on slowly. Long-term complications from high blood sugar include heart disease, strokes, diabetic retinopathy which can result in blindness, kidney failure, and poor blood flow in the limbs which may lead to amputations. The sudden onset of hyperosmolar hyperglycemic state may occur; however, ketoacidosis is uncommon.

<span class="mw-page-title-main">Statin</span> Class of drugs used to lower cholesterol levels

Statins are a class of medications that reduce illness and mortality in people who are at high risk of cardiovascular disease. They are the most commonly prescribed cholesterol-lowering drugs, and are also known as HMG-CoA reductase inhibitors.

Vascular dementia (VaD) is dementia caused by problems in the blood supply to the brain, resulting from a cerebrovascular disease. Restricted blood supply (ischemia) leads to cell and tissue death in the affected region, known as an infarct. The three types of vascular dementia are subcortical vascular dementia, multi-infarct dementia, and stroke related dementia. Subcortical vascular dementia is brought about by damage to the small blood vessels in the brain. Multi-infarct dementia is brought about by a series of mini-strokes where many regions have been affected. The third type is stroke related where more serious damage may result. Such damage leads to varying levels of cognitive decline. When caused by mini-strokes, the decline in cognition is gradual. When due to a stroke, the cognitive decline can be traced back to the event.

<span class="mw-page-title-main">Hypercholesterolemia</span> High levels of cholesterol in the blood

Hypercholesterolemia, also called high cholesterol, is the presence of high levels of cholesterol in the blood. It is a form of hyperlipidemia, hyperlipoproteinemia, and dyslipidemia.

Dyslipidemia is a metabolic disorder characterized by abnormally high or low amounts of any or all lipids or lipoproteins in the blood. Dyslipidemia is a risk factor for the development of atherosclerotic cardiovascular diseases (ASCVD), which include coronary artery disease, cerebrovascular disease, and peripheral artery disease. Although dyslipidemia is a risk factor for ASCVD, abnormal levels don't mean that lipid lowering agents need to be started. Other factors, such as comorbid conditions and lifestyle in addition to dyslipidemia, is considered in a cardiovascular risk assessment. In developed countries, most dyslipidemias are hyperlipidemias; that is, an elevation of lipids in the blood. This is often due to diet and lifestyle. Prolonged elevation of insulin resistance can also lead to dyslipidemia. Likewise, increased levels of O-GlcNAc transferase (OGT) may cause dyslipidemia.

<span class="mw-page-title-main">Diseases of affluence</span> Health conditions thought to be a result of increasing wealth in society

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<span class="mw-page-title-main">Apolipoprotein</span> Proteins that bind lipids to transport them in body fluids

Apolipoproteins are proteins that bind lipids to form lipoproteins. They transport lipids in blood, cerebrospinal fluid and lymph.

Hyperlipidemia is abnormally high levels of any or all lipids or lipoproteins in the blood. The term hyperlipidemia refers to the laboratory finding itself and is also used as an umbrella term covering any of various acquired or genetic disorders that result in that finding. Hyperlipidemia represents a subset of dyslipidemia and a superset of hypercholesterolemia. Hyperlipidemia is usually chronic and requires ongoing medication to control blood lipid levels.

<span class="mw-page-title-main">Streptozotocin</span> Chemical compound

Streptozotocin or streptozocin (STZ) is a naturally occurring alkylating antineoplastic agent that is particularly toxic to the insulin-producing beta cells of the pancreas in mammals. It is used in medicine for treating certain cancers of the islets of Langerhans and used in medical research to produce an animal model for hyperglycemia and Alzheimer's in a large dose, as well as type 2 diabetes or type 1 diabetes with multiple low doses.

The biochemistry of Alzheimer's disease, the most common cause of dementia, is not yet very well understood. Alzheimer's disease (AD) has been identified as a proteopathy: a protein misfolding disease due to the accumulation of abnormally folded amyloid beta (Aβ) protein in the brain. Amyloid beta is a short peptide that is an abnormal proteolytic byproduct of the transmembrane protein amyloid-beta precursor protein (APP), whose function is unclear but thought to be involved in neuronal development. The presenilins are components of proteolytic complex involved in APP processing and degradation.

The prevention of dementia involves reducing the number of risk factors for the development of dementia, and is a global health priority needing a global response. Initiatives include the establishment of the International Research Network on Dementia Prevention (IRNDP) which aims to link researchers in this field globally, and the establishment of the Global Dementia Observatory a web-based data knowledge and exchange platform, which will collate and disseminate key dementia data from members states. Although there is no cure for dementia, it is well established that modifiable risk factors influence both the likelihood of developing dementia and the age at which it is developed. Dementia can be prevented by reducing the risk factors for vascular disease such as diabetes, high blood pressure, obesity, smoking, physical inactivity and depression. A study concluded that more than a third of dementia cases are theoretically preventable. Among older adults both an unfavorable lifestyle and high genetic risk are independently associated with higher dementia risk. A favorable lifestyle is associated with a lower dementia risk, regardless of genetic risk. In 2020, a study identified 12 modifiable lifestyle factors, and the early treatment of acquired hearing loss was estimated as the most significant of these factors, potentially preventing up to 9% of dementia cases.

<span class="mw-page-title-main">Alzheimer's disease</span> Progressive neurodegenerative disease

Alzheimer's disease (AD) is a neurodegenerative disease that usually starts slowly and progressively worsens, and is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As the disease advances, symptoms can include problems with language, disorientation, mood swings, loss of motivation, self-neglect, and behavioral issues. As a person's condition declines, they often withdraw from family and society. Gradually, bodily functions are lost, ultimately leading to death. Although the speed of progression can vary, the average life expectancy following diagnosis is three to twelve years.

Complications of diabetes are secondary diseases that are a result of elevated blood glucose levels that occur in diabetic patients. These complications can be divided into two types: acute and chronic. Acute complications are complications that develop rapidly and can be exemplified as diabetic ketoacidosis (DKA), hyperglycemic hyperosmolar state (HHS), lactic acidosis (LA), and hypoglycemia. Chronic complications develop over time and are generally classified in two categories: microvascular and macrovascular. Microvascular complications include neuropathy, nephropathy, and retinopathy; while cardiovascular disease, stroke, and peripheral vascular disease are included in the macrovascular complications.

Alzheimer's disease (AD) in the Hispanic/Latino population is becoming a topic of interest in AD research as Hispanics and Latinos are disproportionately affected by Alzheimer's Disease and underrepresented in clinical research. AD is a neurodegenerative disease, characterized by the presence of amyloid-beta plaques and neurofibrillary tangles, that causes memory loss and cognitive decline in its patients. However, pathology and symptoms have been shown to manifest differently in Hispanic/Latinos, as different neuroinflammatory markers are expressed and cognitive decline is more pronounced. Additionally, there is a large genetic component of AD, with mutations in the amyloid precursor protein (APP), Apolipoprotein E APOE), presenilin 1 (PSEN1), bridging Integrator 1 (BIN1), SORL1, and Clusterin (CLU) genes increasing one's risk to develop the condition. However, research has shown these high-risk genes have a different effect on Hispanics and Latinos then they do in other racial and ethnic groups. Additionally, this population experiences higher rates of comorbidities, that increase their risk of developing AD. Hispanics and Latinos also face socioeconomic and cultural factors, such as low income and a language barrier, that affect their ability to engage in clinical trials and receive proper care.

Alzheimer's disease (AD) in African Americans is becoming a rising topic of interest in AD care, support, and scientific research, as African Americans are disproportionately affected by AD. Recent research on AD has shown that there are clear disparities in the disease among racial groups, with higher prevalence and incidence in African Americans than the overall average. Pathologies for Alzheimer’s also seem to manifest differently in African Americans, including with neuroinflammation markers, cognitive decline, and biomarkers. Although there are genetic risk factors for Alzheimer’s, these account for few cases in all racial groups.

References

  1. 1 2 3 4 5 6 7 Kandimalla, Ramesh; Thirumala, Vani; Reddy, P. Hemachandra (May 2017). "Is Alzheimer's disease a Type 3 Diabetes? A critical appraisal". Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 1863 (5): 1078–1089. doi:10.1016/j.bbadis.2016.08.018. PMC   5344773 . PMID   27567931.
  2. ↑ de la Monte, Suzanne M.; Wands, Jack R. (2008). "Alzheimer's Disease Is Type 3 Diabetes–Evidence Reviewed". Journal of Diabetes Science and Technology. 2 (6): 1101–1113. doi:10.1177/193229680800200619. PMC   2769828 . PMID   19885299.
  3. 1 2 3 Song, Juhyun; Whitcomb, Daniel J.; Kim, Byeong C. (December 2017). "The role of melatonin in the onset and progression of type 3 diabetes". Molecular Brain. 10 (1): 35. doi: 10.1186/s13041-017-0315-x . PMC   5539639 . PMID   28764741.
  4. ↑ Steen, Eric; Terry, Benjamin M.; Rivera, Enrique J.; Cannon, Jennifer L.; Neely, Thomas R.; Tavares, Rose; Xu, X. Julia; Wands, Jack R.; de la Monte, Suzanne M. (2005). "Impaired insulin and insulin-like growth factor expression and signaling mechanisms in Alzheimer's disease – is this type 3 diabetes?". Journal of Alzheimer's Disease. 7 (1): 63–80. doi:10.3233/JAD-2005-7107. PMID   15750215. S2CID   28173722.
  5. 1 2 "Type 3 diabetes explained". Medical News Today. July 30, 2021.
  6. 1 2 3 4 5 Moheet, Amir; Mangia, Silvia; Seaquist, Elizabeth R. (September 2015). "Impact of diabetes on cognitive function and brain structure: Impact of diabetes on brain". Annals of the New York Academy of Sciences. 1353 (1): 60–71. Bibcode:2015NYASA1353...60M. doi:10.1111/nyas.12807. PMC   4837888 . PMID   26132277.
  7. ↑ Ferreira, Laís S. S.; Fernandes, Caroline S.; Vieira, Marcelo N. N.; De Felice, Fernanda G. (13 November 2018). "Insulin Resistance in Alzheimer's Disease". Frontiers in Neuroscience. 12: 830. doi: 10.3389/fnins.2018.00830 . PMC   6277874 . PMID   30542257.
  8. ↑ Förstl, H.; Kurz, A. (16 December 1999). "Clinical features of Alzheimer's disease". European Archives of Psychiatry and Clinical Neuroscience. 249 (6): 288–290. doi:10.1007/s004060050101. PMID   10653284. S2CID   26142779.
  9. 1 2 3 4 5 6 7 8 Khalsa, Dharma Singh; Perry, George (2017). "The Four Pillars of Alzheimer's Prevention". Cerebrum. v2017 (Mar–Apr): cer03–17. PMC   5501038 . PMID   28698774.
  10. 1 2 3 "What Are the Signs of Alzheimer's Disease?". National Institute on Aging. 16 May 2017.
  11. 1 2 de la Monte, Suzanne M.; Wands, Jack R. (November 2008). "Alzheimer's Disease is Type 3 Diabetes—Evidence Reviewed". Journal of Diabetes Science and Technology. 2 (6): 1101–1113. doi:10.1177/193229680800200619. PMC   2769828 . PMID   19885299.
  12. 1 2 "What is type 3 diabetes?". Diabetesaustralia.com.au. Diabetes Australia. 30 Aug 2019. Retrieved 11 Dec 2023.
  13. 1 2 3 4 Bae, Choon; Song, Juhyun (22 November 2017). "The Role of Glucagon-Like Peptide 1 (GLP1) in Type 3 Diabetes: GLP-1 Controls Insulin Resistance, Neuroinflammation and Neurogenesis in the Brain". International Journal of Molecular Sciences. 18 (11): 2493. doi: 10.3390/ijms18112493 . PMC   5713459 . PMID   29165354.
  14. ↑ Saiz-Vazquez, Olalla; Puente-Martinez, Alicia; Ubillos-Landa, Silvia; Pacheco-Bonrostro, Joaquin; Santabarbara, Javier (18 Jun 2020). "Cholesterol and Alzheimer's Disease Risk: A Meta-Meta-Analysis". Brain Sci. 10 (6): 386. doi: 10.3390/brainsci10060386 . PMC   7349210 . PMID   32570800.
  15. ↑ Karch, Celeste M.; Goate, Alison M. (1 Jan 2015). "Alzheimer's disease risk genes and mechanisms of disease pathogenesis". Biol. Psychiatr. 77 (1): 43–51. doi:10.1016/j.biopsych.2014.05.006. PMC   4234692 . PMID   24951455.
  16. ↑ Jick, H; Zornberg, G.L.; Jick, S.S.; Seshadri, S.; Drachman, D.A. (11 Nov 2000). "Statins and the Risk of Dementia". Lancet. 356 (9242): 1627–1631. doi:10.1016/S0140-6736(00)03155-X. PMID   11089820. S2CID   11414020.
  17. ↑ Ichikawa, Takahiro; Okada, Hiroshi; Hamaguchi, Masahide; Kurogi, Kazushiro; Murata, Hiroaki; Ito, Masato; Fukui, Michiaki (May 2023). "Estimated small dense low-density lipoprotein-cholesterol and incipient type 2 diabetes in Japanese people: Population-based Panasonic cohort study 13". Diab. Res. Clin. Pract. 199: 110665. doi:10.1016/j.diabres.2023.110665. PMID   37031889. S2CID   258047959.
  18. ↑ Verges, Bruno (Dec 2009). "Lipid modification in type 2 diabetes: the role of LDL and HDL". Fundam. Clin. Pharmacol. 23 (6): 681–685. doi:10.1111/j.1472-8206.2009.00739.x. PMID   19650852.
  19. ↑ Montine, Thomas J.; Neely, M. Diana; Quinn, Joseph F.; Beal, M. Flint; Markesbery, William R.; Roberts II, L. Jackson; Morrow, Jason D. (1 Sep 2002). "Lipid peroxidation in aging brain and Alzheimer's disease". Free Radical Biology & Medicine. 33 (5): 620–626. doi:10.1016/S0891-5849(02)00807-9. PMID   12208348.
  20. ↑ Srikanth, Velandai; Arvanitakis, Zoe (2018). Type 2 Diabetes and Dementia. Academic Press. ISBN   978-0-12-809694-9.[ page needed ]
  21. ↑ Srikanth, Velandai; Arvanitakis, Zoe (2018). Type 2 Diabetes and Dementia. Academic Press. ISBN   978-0-12-809694-9.[ page needed ]
  22. 1 2 3 4 5 Staubo, Sara C.; Aakre, Jeremiah A.; Vemuri, Prashanthi; Syrjanen, Jeremy A.; Mielke, Michelle M.; Geda, Yonas E.; Kremers, Walter K.; Machulda, Mary M.; Knopman, David S.; Petersen, Ronald C.; Jack, Clifford R.; Roberts, Rosebud O. (February 2017). "Mediterranean diet, micronutrients and macronutrients, and MRI measures of cortical thickness". Alzheimer's & Dementia. 13 (2): 168–177. doi:10.1016/j.jalz.2016.06.2359. PMC   5259552 . PMID   27461490.
  23. ↑ Miller, Emelie; Johansson, Boo (1 January 2016). "Capability to Paint and Alzheimer's Disease: Relationship to Disease Stages and Instructions". SAGE Open. 6 (1). doi: 10.1177/2158244016631799 .
  24. 1 2 Paillard, Thierry; Rolland, Yves; de Souto Barreto, Philipe (2015). "Protective Effects of Physical Exercise in Alzheimer's Disease and Parkinson's Disease: A Narrative Review". Journal of Clinical Neurology. 11 (3): 212–219. doi:10.3988/jcn.2015.11.3.212. PMC   4507374 . PMID   26174783.
  25. 1 2 Justice, Nicholas J. (1 February 2018). "The relationship between stress and Alzheimer's disease". Neurobiology of Stress. 8: 127–133. doi:10.1016/j.ynstr.2018.04.002. PMC   5991350 . PMID   29888308.
  26. 1 2 Ryff, Carol D.; Singer, Burton H.; Dienberg Love, Gayle (29 September 2004). "Positive health: connecting well–being with biology". Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences. 359 (1449): 1383–1394. doi:10.1098/rstb.2004.1521. PMC   1693417 . PMID   15347530.
  27. ↑ McMullan, Ciaran J.; Schernhammer, Eva S.; Rimm, Eric B.; Hu, Frank B.; Forman, John P. (3 April 2013). "Melatonin Secretion and the Incidence of Type 2 Diabetes". JAMA. 309 (13): 1388–1396. doi: 10.1001/jama.2013.2710 . PMC   3804914 . PMID   23549584.
  28. 1 2 3 Femminella, Grazia Daniela; Bencivenga, Leonardo; Petraglia, Laura; Visaggi, Lucia; Gioia, Lucia; Grieco, Fabrizio Vincenzo; de Lucia, Claudio; Komici, Klara; Corbi, Graziamaria; Edison, Paul; Rengo, Giuseppe; Ferrara, Nicola (2017). "Antidiabetic Drugs in Alzheimer's Disease: Mechanisms of Action and Future Perspectives". Journal of Diabetes Research. 2017: 1–7. doi: 10.1155/2017/7420796 . PMC   5471577 . PMID   28656154.
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