Dementia

Forms of dementia; Alzheimer's dementia; vascular dementia, frontotemporal dementia; dementia epidemiology; dementia symptoms; neurodegenerative disease; primary dementia, secondary dementia,

According to the WHO definition, dementia is understood as an umbrella term/syndrome that encompasses various forms of illnesses associated with progressive impairment and loss of memory and other cognitive/mental abilities.

Accordingly, the term dementia includes

• slowly developing, persisting for at least 6 months,
• chronically progressive neurodegenerative diseases lasting at least 6 months,
• which lead to varying degrees of loss of cognitive functions such as memory, thinking, orientation, language, judgment, attention and concentration, social skills , action planning and behavior.

The disease is increasingly associated with impairment of everyday life and the ability to lead an independent life is increasingly lost, which is a great burden for the patients themselves as well as for their relatives and represents a challenge with regard to the care and support of people suffering from dementia.

The disease is usually not associated with impairments or disturbances of consciousness or sensory perception and can be distinguished from acute, sudden disturbances of brain function, such as delirium, due to the insidious, chronically progressive course of the disease.

In terms of differential diagnosis, it is very important to distinguish between

• primary neurodegenerative forms of dementia (e.g. Alzheimer's dementia, etc.), which are currently incurable, from
• secondary forms of dementia (e.g. metabolic diseases, deficiency symptoms, etc.), which can be improved or cured by treating the underlying disease.

Even if the prevalence increases significantly with age, dementia is not a typical symptom of old age and is not a normal part of the ageing process. Despite age-related physical limitations, people can live to a very old age while retaining their cognitive abilities.

The difference between primary and secondary dementia is important in the differential diagnosis:

Primary dementia : are neurodegenerative diseases (e.g. AD) that develop in the brain. Primary forms of dementia show progression and are not yet curable according to current scientific knowledge, but can only be slightly delayed in their progression and symptoms alleviated by symptomatic treatment.

Secondary dementia: develops due to the effect of other causes on the brain, e.g. other diseases, metabolic disorders, deficiencies, poisoning, etc. and can be prevented or improved by avoiding and treating the causes or the underlying disease.

Different forms of dementia are distinguished:

Alzheimer's dementia ( AD): the most common form of dementia (approx. 60-70%), exact cause and pathophysiology not yet fully understood, several hypotheses are being discussed; a multifactorial process is very likely (including amyloid deposits and tau neurofibril conglomerates are considered to be characteristic, as well as neurochemical reduction of cholinergic neurons and neurotransmitter acetylcholine; genetic risk factors, especially Apo E4 (among others), are found more frequently and may be directly or indirectly related to the occurrence; prevalence increases strongly with age from 70 years.

• A rare familial form of AD (1-5% of all AD cases) with onset before the age of 60 (early onset) is autosomal . (early onset) is inherited autosomal-dominantly (affected genes: APP, PSEN1 or PSEN2 ); early onset of AD often results in more severe symptoms and faster progression.

Due to the prevalence at an advanced age, demographic change is expected to lead to a greater increase in AD worldwide in the near future (especially in developing and emerging countries) and a challenge for healthcare systems and care.

Vascular dementia (VD): prevalence is estimated at 10-15%. Prevalence increases with increasing age from 65 LJ. Strong increase, cardiovascular risk factors and history of stroke or recurrent TIA are characteristic. Loss of function due to progressive loss of brain tissue due to insufficient blood supply, microinfarcts and microbleeds (multi-infarct dementia). Often simultaneous neurological deficits (clinical DD s. Hachinski Ischemic Score (HIS)). AD and vascular dementia often occur simultaneously and therefore make up the majority of dementia cases (Román GC et al 2004, Ravona-Springer R et al 2003).

This group of forms also includes the very rare, familial, hereditary cerebral microangiopathy CADASIL with subcortical infarcts and leukoencephalopathy, which can lead to dementia at a young age (middle adulthood) due to the vacular damage. Recurrent circulatory disorders, TIA, without vascular risk factors e.g. arterial hypertension, frequent migraine, psychiatric symptoms, neurological deficits of subcortical dementia with disorders of cognition, drive, speech etc.; autosomal dominant inheritance(NOTCH3 gene; located on chromosome 19) (Dichgans M et. al. 1997).

Lewy body dementia ( LBD): approx. 10-20 % of all dementia cases and thus a frequent neurodegenerative form of dementia after AD; occurs with increasing age; shows similar symptoms to AD, therefore often not clearly differentiated from Alzheimer's dementia and misdiagnosed or underdiagnosed. Frequency increases after 65 LJ (50-80 J.), predominantly in family history of LBD, men ≥ women (strong variability in the data) (Bonanni L et al 2018, Kosaka K ed. 2017; Taylor JP et al. 2020).

Frontotemporal dementia ( FTD): this is a rarer form of dementia (3-9 %), leads to degeneration of the frontal and temporal lobes; can occur at a younger age up to 65 years (frequent onset between 40-65 years, age range 20-85 years); usually rapid progression. Typical symptoms: initially in the foreground behavioral changes with loss of behavioral control and judgment, often also aggressive behavior or loss of social skills and communication, disorders of speech and language comprehension, memory disorders usually not immediately, but usually only in the later course of the disease. Different variants are supported: behavioral variant of FTD, primary progressive aphasia (PPA), or also with motor symptoms progressive supranuclear palsy, corticobasal degeneration, very rarely also amyotrophic lateral sclerosis with FTD (Logroscino G et al 2023).

Dementia in M . Parkinson's disease: approx. 25-40% of Parkinson's patients also develop dementia in the later course of the disease, the risk increases with age and duration of the disease. Symptoms: cognitive impairments, disturbances in attention, problem solving and planning of action sequences. Symptoms are often masked by the motor impairments of Parkinson's disease. However, differential diagnosis is particularly important, as treatable causes may be present, e.g. due to adverse effects of medication, early dementia excludes Parkinson's diagnosis.

Downsyndrome (trisomy 21): with increasing life expectancy, people with Down syndrome have an increased risk of developing dementia, predominantly AD, and the disease occurs earlier than in the normal population. Frequency: about 30% of 50 year olds and about 50% of 60 year olds develop AD; in autopsy studies, significant amounts of beta-amyloid and tau protein are found in the brain at the age of 40 years in almost all people with Down syndrome, which are considered characteristic of AD, yet not all people with Down syndrome develop symptoms of MCI or even AD (Alzheimers Association 2026). A connection is suspected with the APP gene on chromosome 21, which codes for amyloid precursor protein, which is present 3-fold in Down syndrome and possibly leads to increased amyloid production. Symptoms: Memory loss is usually preceded by changes in drive, personality and social cognition. For easier and early detection of cognitive decline in Down syndrome, a baseline assessment should be routinely performed at 35 years of age. It should also be noted that medications (cholinesterase inhibitors, memantine, no evidence of efficacy to date (Cochraine Review) often work differently or not at all in Down's patients!

Huntington'sdisease: due to an autosomal dominant genetic mutation on chromosome 4 (multiplied CAG triplet), a defective form of the protein huntingtin is produced, which leads to extensive destruction of nerve cells and, as the disease progresses, also to dementia due to the extensive degeneration of various brain regions. In contrast to AD, this is usually a subcortical dementia that initially affects cognitive executive functions and only later memory and other cognitive functions. In Germany, the disease is known in approx. 10,000 people, i.e. already symptomatic; a total of approx. 30,000 people could still be non-symptomatic gene carriers, as the age of onset is between 35-50 years; several hundred new cases per year.

Creutzfeldt - Jakob disease ( CJD): very rare (1-2 cases/1 million/year worldwide), fatal brain disease (spongiform encephalopathy with typical spongy changes in brain tissue) caused by misfolded, infectious proteins (so-called prions) and associated with rapidly progressing dementia and additional deterioration of other brain functions. Sporadic cases, of unknown cause (vast majority of cases), mostly in older people, familial clustered cases of presumably genetic cause, as well as acquired cases iatrogenic (e.g. growth hormone) or caused by internal products of BSE (bovine spongiform encephalopathy; mad cow disease) invented cattle (vCJD) are seen. Symptoms include memory loss, personality changes, coordination disorders and other neurological deficits (e.g. motor function), which occur within a short period of time and progress very quickly to coma and death. Diagnosis based on clinical findings, EEG, MRI, fluid (14-3-3 protein, RT-QuIC). The disease is not treatable. Only supportive and symptomatic treatment (e.g. narcotics, anticonvulsants, etc.). There is no evidence to date that CJD is transmitted through simple physical contact, blood or sexual contact. The disease is notifiable with the exception of the hereditary form (RKI) (see also RKI CJD frequently asked questions).

Dementia in childhood and adolescence: in contrast to developmental delays, this is the loss of already acquired and learned abilities such as motor skills (e.g. walking), coordination, language, cognitive abilities, ability to concentrate, ability to learn and what has already been learned (eating, playing), habits (sleep, etc.), behavior (behavioral abnormalities/behavioral changes), general developmental regression. The brain damage is usually rapidly progressive and is accompanied by a shortened life expectancy (often before reaching adulthood). For the most part, there are currently no treatment options available. Frequency approx. 1 child in 2900 children worldwide. Causes: mostly very rare genetic metabolic diseases; so far ≥140 individual gene mutations; predominantly lysosomal storage diseases or mitochondrial diseases (mitochondriopathies). A database provides information on identified forms, https://www.childhooddementia.org/knowledgebase and https://www.childhooddementia.org/ (Elvidge KL et al 2023, Djafar JV et al 2023).

Secondary forms of dementia.

Definition: Dementia symptoms and diseases which, in contrast to the neurodegenerative primary forms of dementia, are not directly caused by processes in the brain, but are caused by diseases or influences from outside the brain and can be prevented or improved by treating the cause.

Secondary dementias account for approx. 10% of all dementias.

Causes: Vitamin and nutrient deficiencies, e.g. VitB12, B1, B3 (niacin), VitB6, folate/folic acid, possibly also VitD and VitB2, increased homocysteine levels, thyroid dysfunction, poisoning, toxic substances, alcohol and drug effects (e.g. Wernicke-Korsakoff), brain tumors, pseudotumor cerebri (normal pressure hydrocephalus), traumatic causes/craniocerebral trauma, chronic traumatic encephalopathy, chronic infections (HIV, etc.), chronic cardiovascular and metabolic diseases, mental illnesses such as severe depression (pseudodementia).

In addition, environmental factors such as air pollution (e.g. emissions from traffic, industry) and modifiable living conditions can generally have a strong influence on the individual risk of developing dementia.

Modifiable risk factors for dementia according to the Lancet Standing Commission 2024: low education/low educational opportunities, hearing loss, high blood pressure, high LDL cholesterol, high alcohol consumption (≥21 units/week), obesity, smoking, air pollution, visual impairment, depression, social isolation, physical inactivity and diabetes (Livingston G et al 2024).

Examples of secondary forms of dementia:

Korsakow syndrome: approx. 1-3 % (according to autopsy results), up to approx. 12 % with alcoholism (combined malnutrition and B1 absorption disorder). Dementia due to severe, irreversible brain damage as a result of chronic vitamin B1 deficiency (thiamine deficiency). Memory disorders (amnesia, especially anterograde amnesia), confusion, confabulation and disorientation; often preceded by acute vitamin B1 deficiency in the form of Wernicke's encephalopathy (at this stage still curable by immediate thiamine substitution) or symptoms coexist as Wernicke-Korsakov syndrome; common in alcohol dependence, but also malnutrition, anorexia nervosa, gastrointestinal diseases, cancer, dialysis, brain diseases, etc.

Chronic traumatic encephalopathy(CTE): chronic progressive neurodegenerative brain damage, triggered by repeated traumatic brain injuries (TBI), even mild repeated TBI, repeated blows and impacts to the head are sufficient causes, problem known in professional sports such as boxing, rugby, soccer (headers), football, etc, Brain atrophy and deposits (tau protein), symptoms: gradual, often long latency period (10-20 years). Cognitive disorders, mental disorders such as depression, irritability, suicidal tendencies, motor skills often also affected with symptoms similar to Parkinson's ("dementia pugilistica"/"boxer's dementia"), possibly also earlier and more frequent occurrence. Possible earlier and more frequent occurrence of AD, ALS compared with normal population; frequency not clearly defined, as clear diagnosis only after autopsy and only small number of examinations.

Autoimmune encephalitis: most common cause of rapidly progressive dementia; requires early diagnosis and treatment (Wesley SF, Ferguson D. 2019).

According to WHO, global figures are rising sharply. In 2021, around 57 million people worldwide were affected by dementia; almost 10 million new cases every year;

Predicted increase to 78 million by 2030 and 152 million by 2050 worldwide (GBD 2019, Lancet Public Health 2022) due to demographic change and changing living conditions, a considerable proportion of the increase is expected in developing and emerging countries (approx. 60%)

socio-economically, women are more negatively affected not only as sufferers, but also due to their role as caregivers.

Dementia is a major cause of disability and care dependency and the 7th most common cause of death worldwide, associated with considerable economic costs,

The potential of prevention through modifiable risk factors, lifestyle changes and healthy ageing is seen as crucial (WHO Dementia 2025, Lancet Standing Commission 2024).

In Germany, there were an estimated 1.8 million people with dementia and around 360,000-440,000 new cases of dementia as at December 31, 2021.

In 2033, it is estimated that between 1.65 and 2 million people aged 65 and over could be affected (Blotenberg I et al 2023).

It is calculated that 38% of cases are associated with 11 potentially modifiable risk factors; an estimated 15% reduction in the prevalence of risk factors could reduce the number of cases by up to 138,000 in 2033 (taking into account the Lancet Commission's risk factors: low education, hearing loss, high blood pressure, excessive alcohol consumption, obesity, smoking, depression, social isolation, physical inactivity, air pollution and diabetes.

(Data based on estimates, as there is no dementia register in Germany, figures probably underestimated, dementia is also underdiagnosed) (Blotenberg I et al 2023).

(see also RKI topic page on dementia with studies on the situation in Germany).