Editing Dementia (section)

==Causes==
Many causes of dementia are [[neurodegenerative]], and [[protein misfolding]] is a cardinal feature of these.<ref name=Chung>{{cite journal |vauthors=Chung CG, Lee H, Lee SB |title=Mechanisms of protein toxicity in neurodegenerative diseases |journal=Cell Mol Life Sci |volume=75 |issue=17 |pages=3159–3180 |date=September 2018 |pmid=29947927 |pmc=6063327 |doi=10.1007/s00018-018-2854-4}}</ref> Other common causes include vascular dementia, dementia with Lewy bodies, frontotemporal dementia, and mixed dementia (commonly Alzheimer's disease and vascular dementia).<ref name="WHO2022"/>{{efn|Kosaka (2017) writes: "Dementia with Lewy bodies (DLB) is now well known to be the second most frequent dementia following Alzheimer disease (AD). Of all types of dementia, AD is known to account for about 50%, DLB about 20% and vascular dementia (VD) about 15%. Thus, AD, DLB, and VD are now considered to be the three major dementias."<ref>{{cite book |veditors=Kosaka K |editor-link=Kenji Kosaka (psychiatrist) |date=2017 |title=Dementia with Lewy bodies: clinical and biological aspects |edition=1st |publisher=Springer: Japan |doi=10.1007/978-4-431-55948-1 |isbn=978-4-431-55948-1 |s2cid=45950966}}</ref><!-- Page v --> The NINDS (2020) says that Lewy body dementia "is one of the most common causes of dementia, after Alzheimer's disease and vascular disease."<ref name= NINDS2020Book>{{cite web |title=Lewy body dementia: Hope through research |url=https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Hope-Through-Research/Lewy-Body-Dementia-Hope-Through-Research |website=National Institute of Neurological Disorders and Stroke |publisher=US National Institutes of Health |access-date=March 18, 2020 |date=January 10, 2020}}</ref> Hershey (2019) says, "DLB is the third most common of all the neurodegenerative diseases behind both Alzheimer's disease and Parkinson's disease".<ref>{{cite journal |vauthors=Hershey LA, Coleman-Jackson R |title=Pharmacological management of dementia with Lewy dodies |journal=Drugs Aging |volume=36 |issue=4 |pages=309–319 |date=April 2019 |pmid=30680679 |pmc=6435621 |doi=10.1007/s40266-018-00636-7 |type= Review}}</ref><!-- Page 309 -->}}<ref name=":1" /> Less common causes include [[normal pressure hydrocephalus]], [[Parkinson's disease dementia]], [[syphilis]], [[HIV dementia|HIV]], and [[Creutzfeldt–Jakob disease]].<ref>{{cite book |vauthors=Gauthier S |title=Clinical diagnosis and management of Alzheimer's disease |date=2006 |publisher=Informa Healthcare |location=Abingdon, Oxon |isbn=978-0-203-93171-4 |pages=53–54 |edition=3rd |url=https://books.google.com/books?id=a221hX4WuwUC&pg=PA54 |url-status=live |archive-url=https://web.archive.org/web/20160503111047/https://books.google.com/books?id=a221hX4WuwUC&pg=PA54|archive-date=May 3, 2016}}</ref>

=== Alzheimer's disease ===
{{Main|Alzheimer's disease}}
[[File:Alzheimers brain.jpg|thumb|Brain [[atrophy]] in severe Alzheimer's]]

Alzheimer's disease accounts for 60–70% of cases of dementia worldwide. The most common symptoms of Alzheimer's disease are [[short-term memory loss]] and [[Anomic aphasia|word-finding difficulties]]. Trouble with [[visuospatial function]]ing (getting lost often), reasoning, judgment and [[insight]] fail. Insight refers to whether or not the person realizes they have memory problems.

The part of the brain most affected by Alzheimer's is the [[hippocampus]]. Other parts that show [[atrophy]] (shrinking) include the [[Temporal lobe|temporal]] and [[parietal lobe]]s. Although this pattern of brain shrinkage suggests Alzheimer's, it is variable and a brain scan is insufficient for a diagnosis.

Little is known about the events that occur during and that actually cause Alzheimer's disease. This is due to the fact that, historically, brain tissue from people with the disease could only be studied after the person's death. Brain scans can now help diagnose and distinguish between different kinds of dementia and show severity. These include magnetic resonance imaging (MRI), computerized tomography (CT), and positron emission tomography (PET).  However, it is known that one of the first aspects of Alzheimer's disease is overproduction of [[amyloid]]. Extracellular senile plaques (SPs), consisting of beta-amyloid (Aβ) peptides, and intracellular [[neurofibrillary tangle]]s (NFTs) that are formed by hyperphosphorylated tau proteins, are two well-established pathological hallmarks of AD.<ref>{{cite journal | vauthors = Abyadeh M, Gupta V, Chitranshi N, Gupta V, Wu Y, Saks D, Wander Wall R, Fitzhenry MJ, Basavarajappa D, You Y, Salekdeh GH, Haynes PA, Graham SL, Mirzaei M | display-authors = 6 | title = Mitochondrial dysfunction in Alzheimer's disease – a proteomics perspective | journal = Expert Review of Proteomics | volume = 18 | issue = 4 | pages = 295–304 | date = April 2021 | pmid = 33874826 | doi = 10.1080/14789450.2021.1918550 | s2cid = 233310698 }}</ref> Amyloid causes [[inflammation]] around the [[Amyloid plaques|senile plaques of the brain]], and too much buildup of this inflammation leads to changes in the brain that cannot be controlled, leading to the symptoms of Alzheimer's.<ref>{{cite journal | vauthors = Wenk GL | title = Neuropathologic changes in Alzheimer's disease | journal = The Journal of Clinical Psychiatry | volume = 64 | issue = Suppl 9 | pages = 7–10 | date = 2003 | pmid = 12934968 | url = http://www.psychiatrist.com/jcp/article/pages/2003/v64s09/v64s0902.aspx }}</ref>

Several articles have been published on a possible relationship (as an either primary cause or exacerbation of Alzheimer's disease) between general [[anesthesia]] and Alzheimer's in specifically [[the elderly]].<ref>{{cite journal | vauthors = Papon MA, Whittington RA, El-Khoury NB, Planel E | title = Alzheimer's disease and anesthesia | journal = Frontiers in Neuroscience | volume = 4 | page = 272 | date = 2011 | pmid = 21344011 | pmc = 3034231 | doi = 10.3389/fnins.2010.00272 | doi-access = free }}</ref>

=== Vascular ===
{{Main|Vascular dementia}}

Vascular dementia accounts for at least 20% of dementia cases, making it the second most common type.<ref name=pmid24267647>{{cite journal | vauthors = Iadecola C | title = The pathobiology of vascular dementia | journal = Neuron | volume = 80 | issue = 4 | pages = 844–866 | date = November 2013 | pmid = 24267647 | pmc = 3842016 | doi = 10.1016/j.neuron.2013.10.008 }}</ref> It is caused by disease or injury affecting the [[cerebral circulation|blood supply to the brain]], typically involving a series of [[mini-stroke]]s. The symptoms of this dementia depend on where in the brain the strokes occurred and whether the blood vessels affected were large or small.<ref name="Memory Loss"/> Repeated injury can cause progressive dementia over time, while a single injury located in an area critical for cognition such as the hippocampus, or thalamus, can lead to sudden cognitive decline.<ref name=pmid24267647 /> Elements of vascular dementia may be present in all other forms of dementia.<ref name=Baskys>{{cite journal |vauthors=Baskys A, Cheng JX |title=Pharmacological prevention and treatment of vascular dementia: approaches and perspectives |journal=Exp Gerontol |volume=47 |issue=11 |pages=887–891 |date=November 2012 |pmid=22796225 |doi=10.1016/j.exger.2012.07.002 |s2cid=1153876}}</ref>

[[Neuroimaging|Brain scans]] may show evidence of multiple strokes of different sizes in various locations. People with vascular dementia tend to have risk factors for [[vascular disease|disease of the blood vessels]], such as [[tobacco use]], [[high blood pressure]], [[atrial fibrillation]], [[Hypercholesterolemia|high cholesterol]], [[diabetes]], or other signs of vascular disease such as a previous heart attack or [[angina]].<ref>{{Cite web|title=Vascular dementia – Symptoms and causes|url=https://www.mayoclinic.org/diseases-conditions/vascular-dementia/symptoms-causes/syc-20378793|access-date=July 8, 2021|website=Mayo Clinic|language=en}}</ref>

=== Lewy bodies ===
{{Main|Dementia with Lewy bodies}}

The prodromal symptoms of dementia with Lewy bodies (DLB) include [[mild cognitive impairment]], and [[delirium]] onset.<ref name="McKeith">{{cite journal |vauthors=McKeith IG, Ferman TJ, Thomas AJ, et al |title=Research criteria for the diagnosis of prodromal dementia with Lewy bodies |journal=Neurology |volume=94 |issue=17 |pages=743–755 |date=April 2020 |pmid=32241955 |pmc=7274845 |doi=10.1212/WNL.0000000000009323}}</ref>
The symptoms of DLB are more frequent, more severe, and earlier presenting than in the other dementia subtypes.<ref name="Jurek">{{cite journal |vauthors=Jurek L, Herrmann M, Bonze M et al. |title=Behavioral and psychological symptoms in Lewy body disease: a review |journal= Gériatrie et Psychologie Neuropsychiatrie du Vieillissement|volume=16 |issue=1 |pages=87–95 |date=March 1, 2018 |pmid=29569570 |doi=10.1684/pnv.2018.0723 }}</ref>
Dementia with Lewy bodies has the primary symptoms of fluctuating cognition, alertness or attention; [[REM sleep behavior disorder]] (RBD); one or more of the main features of [[parkinsonism]], not due to medication or stroke; and repeated visual hallucinations.<ref name= McKeithConsensus2017>{{cite journal |vauthors=McKeith IG, Boeve BF, Dickson DW, et al |title=Diagnosis and management of dementia with Lewy bodies: Fourth consensus report of the DLB Consortium |journal=Neurology |volume=89 |issue=1 |pages=88–100 |date=July 2017 |pmid=28592453 |pmc=5496518 |doi=10.1212/WNL.0000000000004058 |type=Review}}</ref> The visual hallucinations in DLB are generally vivid hallucinations of people or animals and they often occur when someone is about to fall asleep or wake up. Other prominent symptoms include problems with planning (executive function) and difficulty with visual-spatial function,<ref name="Memory Loss" /> and disruption in [[autonomic nervous system|autonomic bodily functions]].<ref name= Taylor2020>{{cite journal |vauthors=Taylor JP, McKeith IG, Burn DJ et al |title=New evidence on the management of Lewy body dementia |journal=Lancet Neurol |volume=19 |issue=2 |pages=157–169 |date=February 2020 |pmid=31519472 |doi=10.1016/S1474-4422(19)30153-X |pmc=7017451 |type= Review }} Courtesty link available [https://ore.exeter.ac.uk/repository/bitstream/handle/10871/36535/Management%20Lewy%20body%20dementia_versionsubmittedtoTLNwithappendix.pdf?sequence=10&isAllowed=y here.]</ref> Abnormal sleep behaviors may begin before cognitive decline is observed and are a core feature of DLB.<ref name= McKeithConsensus2017/> RBD is diagnosed either by sleep study recording or, when sleep studies cannot be performed, by medical history and validated questionnaires.<ref name= McKeithConsensus2017/>

=== Parkinson's disease ===
[[Parkinson's disease]] is associated with [[Lewy body dementia]] that often progresses to [[Parkinson's disease dementia]] following a period of dementia-free Parkinson's disease.<ref name=Gomperts>{{cite journal |vauthors=Gomperts SN |title=Lewy Body Dementias: Dementia With Lewy Bodies and Parkinson Disease Dementia |journal=Continuum (Minneap Minn) |volume=22 |issue=2 Dementia |pages=435–463 |date=April 2016 |pmid=27042903 |pmc=5390937 |doi=10.1212/CON.0000000000000309|type=Review}}</ref>

=== Frontotemporal ===
{{Main|Frontotemporal dementia}}

Frontotemporal dementias (FTDs) are characterized by drastic personality changes and language difficulties. In all FTDs, the person has a relatively early social withdrawal and early lack of insight. Memory problems are not a main feature.<ref name="Memory Loss" /><ref>{{cite journal | vauthors = Finger EC | title = Frontotemporal Dementias | journal = Continuum | volume = 22 | issue = 2 Dementia | pages = 464–489 | date = April 2016 | pmid = 27042904 | pmc = 5390934 | doi = 10.1212/CON.0000000000000300 }}</ref> There are six main types of FTD. The first has major symptoms in personality and behavior. This is called [[Frontotemporal dementia#Behavioral variant frontotemporal dementia|behavioral variant FTD]] (bv-FTD) and is the most common. The hallmark feature of bv-FTD is [[impulsive behavior]], and this can be detected in pre-dementia states.<ref name="Bateman" /> In bv-FTD, the person shows a change in personal hygiene, becomes rigid in their thinking, and rarely acknowledges problems; they are socially withdrawn, and often have a drastic increase in appetite. They may become socially inappropriate. For example, they may make inappropriate sexual comments, or may begin using pornography openly. One of the most common signs is [[apathy]], or not caring about anything. Apathy, however, is a common symptom in many dementias.<ref name="Memory Loss" />

Two types of FTD feature [[aphasia]] (language problems) as the main symptom. One type is called semantic variant primary progressive aphasia (SV-PPA). The main feature of this is the loss of the meaning of words. It may begin with difficulty naming things. The person eventually may lose the meaning of objects as well. For example, a drawing of a bird, dog, and an airplane in someone with FTD may all appear almost the same.<ref name="Memory Loss" /> In a classic test for this, a person is shown a picture of a pyramid and below it a picture of both a palm tree and a pine tree. The person is asked to say which one goes best with the pyramid. In SV-PPA the person cannot answer that question. The other type is called non-fluent agrammatic variant primary progressive aphasia (NFA-PPA). This is mainly a problem with producing speech. They have trouble finding the right words, but mostly they have a difficulty coordinating the muscles they need to speak. Eventually, someone with NFA-PPA only uses one-syllable words or may become totally mute.

A frontotemporal dementia associated with [[amyotrophic lateral sclerosis]] (ALS) known as (FTD-ALS) includes the symptoms of FTD (behavior, language and movement problems) co-occurring with [[amyotrophic lateral sclerosis]] (loss of motor neurons). Two FTD-related disorders are [[progressive supranuclear palsy]] (also classed as a Parkinson-plus syndrome),<ref name=PS>{{Cite web|title=Progressive Supranuclear Palsy Fact Sheet {{!}} National Institute of Neurological Disorders and Stroke|url=https://www.ninds.nih.gov/disorders/patient-caregiver-education/fact-sheets/progressive-supranuclear-palsy-fact-sheet#:~:text=Progressive%20supranuclear%20palsy%20(PSP)%20is,nerve%20cells%20in%20the%20brain.|access-date=January 20, 2021 |website=ninds.nih.gov}}</ref><ref name=Acta2>{{cite journal |vauthors=Lopez G, Bayulkem K, Hallett M |title=Progressive supranuclear palsy (PSP): Richardson syndrome and other PSP variants |journal=Acta Neurol Scand |volume=134 |issue=4 |pages=242–249 |date=October 2016 |pmid=27070344 |pmc=7292631 |doi=10.1111/ane.12546}}</ref> and [[corticobasal degeneration]].<ref name="Memory Loss" /> These disorders are tau-associated.

=== Huntington's disease ===
{{Main|Huntington's disease}}

Huntington's disease is a [[neurodegenerative disease]] caused by mutations in a single gene ''HTT'', that encodes for [[huntingtin]] protein. Symptoms include cognitive impairment and this usually declines further into dementia.<ref name=Frank2014>{{cite journal | vauthors = Frank S | title = Treatment of Huntington's disease | journal = Neurotherapeutics | volume = 11 | issue = 1 | pages = 153–160 | date = January 2014 | pmid = 24366610 | pmc = 3899480 | doi = 10.1007/s13311-013-0244-z}}</ref>

The first main symptoms of Huntington's disease often include:

* difficulty concentrating
* memory lapses
* depression - this can include low mood, lack of interest in things, or just abnormal feelings of hopelessness
* stumbling and clumsiness that is out of the ordinary
* mood swings, such as irritability or aggressive behavior to insignificant things<ref>{{Cite web |date=February 16, 2018 |title=Huntington's disease – Symptoms |url=https://www.nhs.uk/conditions/huntingtons-disease/symptoms/ |access-date=June 28, 2022 |website=nhs.uk |language=en}}</ref>

=== HIV ===
{{Main|HIV-associated neurocognitive disorder}}

HIV-associated dementia results as a late stage from [[HIV infection]], and mostly affects younger people.<ref name="MSD2019"/> The essential features of HIV-associated dementia are disabling cognitive impairment accompanied by motor dysfunction, speech problems and behavioral change.<ref name="MSD2019">{{cite web |title=HIV-Associated Dementia – Neurologic Disorders |url=https://www.msdmanuals.com/professional/neurologic-disorders/delirium-and-dementia/hiv-associated-dementia |website=MSD Manual Professional Edition |language=en}}</ref> Cognitive impairment is characterised by mental slowness, trouble with [[memory]] and poor [[Attentional control|concentration]]. Motor symptoms include a loss of fine motor control leading to clumsiness, poor balance and tremors. Behavioral changes may include [[apathy]], [[lethargy]] and diminished emotional responses and spontaneity. [[histopathology|Histopathologically]], it is identified by the infiltration of [[monocyte]]s and [[macrophage]]s into the [[central nervous system]] (CNS), [[gliosis]], pallor of [[myelin sheath]]s, abnormalities of [[dendritic cell|dendritic]] processes and [[neuron]]al loss.<ref name=Gray>{{cite journal | vauthors = Gray F, Adle-Biassette H, Chretien F, Lorin de la Grandmaison G, Force G, Keohane C | title = Neuropathology and neurodegeneration in human immunodeficiency virus infection. Pathogenesis of HIV-induced lesions of the brain, correlations with HIV-associated disorders and modifications according to treatments | journal = Clinical Neuropathology | volume = 20 | issue = 4 | pages = 146–155 | year = 2001 | pmid = 11495003 }}</ref>

=== Creutzfeldt–Jakob disease ===
{{Main|Creutzfeldt–Jakob disease}}

Creutzfeldt–Jakob disease is a rapidly progressive [[prion disease]] that typically causes dementia that worsens over weeks to months. [[Prion]]s are disease-causing pathogens created from abnormal proteins.<ref>{{cite journal | vauthors = Collinge J | title = Molecular neurology of prion disease | journal = Journal of Neurology, Neurosurgery, and Psychiatry | volume = 76 | issue = 7 | pages = 906–919 | date = July 2005 | pmid = 15965195 | pmc = 1739714 | doi = 10.1136/jnnp.2004.048660 }}</ref>

=== Alcoholism ===
{{Main|Alcohol-related dementia}}

Alcohol-related dementia, also called alcohol-related brain damage, occurs as a result of excessive use of [[alcohol (drug)|alcohol]] particularly as a substance abuse disorder. Different factors can be involved in this development including [[thiamine deficiency]] and age vulnerability.<ref name=Ridley>{{cite journal |vauthors=Ridley NJ, Draper B, Withall A |title=Alcohol-related dementia: an update of the evidence |journal=Alzheimers Res Ther |volume=5 |issue=1 |page=3 |date=2013 |pmid=23347747 |pmc=3580328 |doi=10.1186/alzrt157 |doi-access=free }}</ref><ref name=Nunes>{{cite book |vauthors=Nunes PT, Kipp BT, Reitz NL, Savage LM |title=Late Aging Associated Changes in Alcohol Sensitivity, Neurobehavioral Function, and Neuroinflammation |chapter=Aging with alcohol-related brain damage: Critical brain circuits associated with cognitive dysfunction |series=International Review of Neurobiology |volume=148 |pages=101–168 |date=2019 |pmid=31733663 |pmc=7372724 |doi=10.1016/bs.irn.2019.09.002 |isbn=978-0-12-817530-9 }}</ref> A degree of brain damage is seen in more than 70% of those with [[alcohol use disorder]]. Brain regions affected are similar to those that are affected by aging, and also by Alzheimer's disease. Regions showing loss of volume include the frontal, temporal, and parietal lobes, as well as the cerebellum, thalamus, and hippocampus.<ref name=Nunes/> This loss can be more notable, with greater cognitive impairments seen in those aged 65 years and older.<ref name=Nunes/>

=== Mixed dementia ===
More than one type of dementia, known as mixed dementia, may exist together in about 10% of dementia cases.<ref name="WHO2022"/> The most common type of mixed dementia is Alzheimer's disease and vascular dementia.<ref>{{Cite web|title=What is mixed dementia?|url=https://www.alzheimers.org.uk/blog/what-is-mixed-dementia|access-date=December 13, 2020|website=Alzheimer's Society|language=en}}</ref> This particular type of mixed dementia's main onsets are a mixture of old age, high blood pressure, and damage to blood vessels in the brain.<ref name="DementiaUK"/>

Diagnosis of mixed dementia can be difficult, as often only one type will predominate. This makes the treatment of people with mixed dementia uncommon, with many people missing out on potentially helpful treatments. Mixed dementia can mean that symptoms onset earlier, and worsen more quickly since more parts of the brain will be affected.<ref name="DementiaUK"/>

=== Other ===
Chronic [[inflammatory condition]]s that may affect the brain and cognition include [[Behçet's disease]], [[multiple sclerosis]], [[sarcoidosis]], [[Sjögren's syndrome]], [[lupus]], [[celiac disease]], and [[non-celiac gluten sensitivity]].<ref name=Schofield2005>{{cite journal | vauthors = Schofield P | title = Dementia associated with toxic causes and autoimmune disease | journal = International Psychogeriatrics | volume = 17 | issue = Suppl 1 | pages = S129–S147 | year = 2005 | pmid = 16240488 | doi = 10.1017/s1041610205001997 | hdl = 1959.13/24647 | s2cid = 11864913 | type = Review | hdl-access = free }}</ref><ref name=RosenbloomSmith2009>{{cite journal | vauthors = Rosenbloom MH, Smith S, Akdal G, Geschwind MD | title = Immunologically mediated dementias | journal = Current Neurology and Neuroscience Reports | volume = 9 | issue = 5 | pages = 359–367 | date = September 2009 | pmid = 19664365 | pmc = 2832614 | doi = 10.1007/s11910-009-0053-2 | type = Review }}</ref> These types of dementias can rapidly progress, but usually have a good response to early treatment. This consists of [[immunomodulators]] or [[steroid]] administration, or in certain cases, the elimination of the causative agent.<ref name=RosenbloomSmith2009 />

Celiac disease does not seem to raise the risk of dementia in general but it may increase the risk of vascular dementia.<ref name="ZisHadjivassiliou2019" /> Both celiac disease or non-celiac gluten sensitivity might raise the risk of cognitive impairment which can be one of the early signs of subsequent dementia.<ref name="MakhloufMesselmani2018">{{cite journal |vauthors=Makhlouf S, Messelmani M, Zaouali J, Mrissa R |year=2018 |title=Cognitive impairment in celiac disease and non-celiac gluten sensitivity: review of literature on the main cognitive impairments, the imaging and the effect of gluten free diet. |journal=Acta Neurol Belg |type=Review |volume=118 |issue=1 |pages=21–27 |doi=10.1007/s13760-017-0870-z |pmid=29247390 |s2cid=3943047}}</ref> A strict [[gluten-free diet]] started early may protect against dementia associated with [[gluten-related disorders]].<ref name="ZisHadjivassiliou2019" /><ref name="MakhloufMesselmani2018" />

Cases of easily reversible dementia include [[hypothyroidism]], [[vitamin B12 deficiency|vitamin B<sub>12</sub> deficiency]], [[Lyme disease]], and [[neurosyphilis]]. For Lyme disease and neurosyphilis, testing should be done if risk factors are present. Because risk factors are often difficult to determine, testing for neurosyphilis and Lyme disease, as well as other mentioned factors, may be undertaken as a matter of course where dementia is suspected.<ref name="Memory Loss" />{{rp|31–32}}

Many other medical and neurological conditions include dementia only late in the illness. For example, a proportion of people with [[Parkinson's disease]] develop dementia, though widely varying figures are quoted for this proportion.<ref name=AarslandKurz2010>{{cite journal | vauthors = Aarsland D, Kurz MW | title = The epidemiology of dementia associated with Parkinson disease | journal = Journal of the Neurological Sciences | volume = 289 | issue = 1–2 | pages = 18–22 | date = February 2010 | pmid = 19733364 | doi = 10.1016/j.jns.2009.08.034 | type = Review | s2cid = 24541533 }}</ref> When dementia occurs in Parkinson's disease, the underlying cause may be [[dementia with Lewy bodies]] or [[Alzheimer's disease]], or both.<ref name=pmid17101891>{{cite journal | vauthors = Galvin JE, Pollack J, Morris JC | title = Clinical phenotype of Parkinson disease dementia | journal = Neurology | volume = 67 | issue = 9 | pages = 1605–1611 | date = November 2006 | pmid = 17101891 | doi = 10.1212/01.wnl.0000242630.52203.8f | s2cid = 25023606 }}</ref> Cognitive impairment also occurs in the Parkinson-plus syndromes of [[progressive supranuclear palsy]] and [[corticobasal degeneration]] (and the same underlying pathology may cause the clinical syndromes of [[frontotemporal lobar degeneration]]). Although the acute [[porphyria]]s may cause episodes of confusion and psychiatric disturbance, dementia is a rare feature of these rare diseases. [[Limbic-predominant age-related TDP-43 encephalopathy]] (LATE) is a type of dementia that primarily affects people in their 80s or 90s and in which [[TDP-43]] protein deposits in the [[limbic]] portion of the brain.<ref>{{cite journal | vauthors = Abbasi J | title = Debate Sparks Over LATE, a Recently Recognized Dementia | journal = JAMA | volume = 322 | issue = 10 | pages = 914–916 | date = September 2019 | pmid = 31433447 | doi = 10.1001/jama.2019.12232 | s2cid = 201118832 }}</ref>

[[Hereditary disorder]]s that can also cause dementia include: some [[metabolic disorder]]s such as [[lysosomal storage disorder]]s, [[Leukodystrophies#Types|leukodystrophies]], and [[spinocerebellar ataxia]]s.

Persistent loneliness may significantly increase the risk of dementia.<ref>{{Cite web |last=Mundell |first=Ernie |date=2024-10-10 |title=Loneliness Raises Odds for Dementia by 31% |url=https://www.healthday.com/health-news/mental-health/loneliness-raises-odds-for-dementia-by-31 |access-date=2024-10-12 |website=www.healthday.com |language=en}}</ref><ref name=PMC11722644>{{Cite journal |last1=Luchetti |first1=Martina |last2=Aschwanden |first2=Damaris |last3=Sesker |first3=Amanda A. |last4=Zhu |first4=Xianghe |last5=O'Súilleabháin |first5=Páraic S. |last6=Stephan |first6=Yannick |last7=Terracciano |first7=Antonio |last8=Sutin |first8=Angelina R. |date=2024-10-09 |title=A meta-analysis of loneliness and risk of dementia using longitudinal data from >600,000 individuals |journal=Nature Mental Health |language=en |volume=2 |issue=11 |pages=1350–1361 |doi=10.1038/s44220-024-00328-9 |issn=2731-6076 |pmc=11722644 |pmid=39802418|pmc-embargo-date=November 1, 2025 }}</ref> Loneliness is associated with a 31% higher likelihood of developing any form of dementia, and can also raise the risk of cognitive impairment by 15%.<ref name=PMC11722644/>